← Back to patent-cliff list
Paclitaxel
Tier B — Position earlyPaclitaxel
National Institutes of Health (NIH)
Originator
1992
First approval
-
Expiry (public)
$1.54B ▲
Peak sales
Small molecule
Type
Targets：Tubulin
Brand：Genetaxyl, Taxol, Xorane, Paxene, Onxal, Padexol, Paxceed, Genaxol, OncoGel, Apealea, Nanotaxel, Genexol, Paclical, Pacligel, Yewtaxan, NanoPac, Paxoral (oral formulation), Anzatax, Nanotax
Indications (approved)：Pancreatic cancer, Non-small cell lung cancer, Hodgkin's disease, Seminoma, Ovarian cancer, Breast cancer, Oesophageal cancer, Head and neck cancer
Regional status
US
Approved
1992-12-29
EU
Phase III
2004-07-01
China
Approved
1996-01-01
Japan
No progress
2005-06-30
Factories producing this API2
Factories registered as producing this API in our sourcing network (RFQ records + product master), sorted by RFQ activity; the snapshot carries no cost or customer data.
2 producing factories on file — sign in to view the named list (factory details are not shown to guests).
Sign in to view factories →Synthetic routes & intermediates112 routes
Originator routes × 0Optimised (non-patent) × 112Process routes × 0
Routes are ordered originator first, then optimised / process (non-patent) routes; each lists steps, overall yield and the intermediate table (code / CAS / name) — ready for supplier sourcing and RFQ. Rendered by this site from structured data; no third-party route graphics used.
OptimisedRoute 1Steps 6 · Total yield /
PACL-00127548-93-2PACL-00217341-93-4PACL-003103150-33-0PACL-004102-94-3PACL-005—PACL-006114915-13-8PACL-007114915-15-0PACL-00898-88-4PACL-009114915-17-2Paclitaxel33069-62-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| PACL-001 | 27548-93-2 | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12-(benzoyloxy)-4,9,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
| PACL-002 | 17341-93-4Available | 2,2,2-trichloroethyl carbonochloridate |
| PACL-003 | 103150-33-0 | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12-(benzoyloxy)-9,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-4-(((2,2,2-trichloroethoxy)carbonyl)oxy)-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
| PACL-004 | 102-94-3 | (Z)-3-phenylacrylic acid |
| PACL-005 | - | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12-(benzoyloxy)-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-9-(((Z)-3-phenylacryloyl)oxy)-4-(((2,2,2-trichloroethoxy)carbonyl)oxy)-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
| PACL-006 | 114915-13-8 | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12-(benzoyloxy)-9-(((2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoyl)oxy)-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-4-(((2,2,2-trichloroethoxy)carbonyl)oxy)-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
| PACL-007 | 114915-15-0 | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-9-(((2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-4-(((2,2,2-trichloroethoxy)carbonyl)oxy)-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
| PACL-008 | 98-88-4 | benzoyl chloride |
| PACL-009 | 114915-17-2 | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-9-(((2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-4-(((2,2,2-trichloroethoxy)carbonyl)oxy)-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
| Paclitaxel | 33069-62-4 | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-9-(((2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl)oxy)-12-(benzoyloxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-3,4,4a,5,6,9,10,11,12,12a-decahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxete-6,12b(2aH)-diyl diacetate |
OptimisedRoute 2Steps 6 · Total yield /
(I)101438-1-a27548-93-2(II)101438-1-a103150-33-0(III)101438-1-a140-10-3(IV)101438-1-a—(VI)101438-1-a—(VII)101438-1-a—(VIII)101438-1-a—101438-1-a98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-1-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-1-a | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-1-a | 140-10-3 | (2E)-3-Phenylacrylic acid |
| (IV)101438-1-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-{[(2Z)-3-phenylprop-2-enoyl]oxy}-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VI)101438-1-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[(3-{[(tert-butoxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VII)101438-1-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[(3-amino-2-hydroxy-3-phenylpropanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VIII)101438-1-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-15-{[2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| 101438-1-a | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 3Steps 9 · Total yield /
(I)101438-2-a783-08-4(II)101438-2-a13831-31-7(III)101438-2-a146924-90-5(IV)101438-2-a144790-01-2(IX)101438-2-a98-88-4(VI)101438-2-a132127-34-5(VII)101438-2-a109-92-2(VIII)101438-2-a201856-48-6(X)101438-2-a201856-53-3(XI)101438-2-a216094-54-1(XII)101438-2-a182072-57-7(XIII)101438-2-a32981-86-5(XIV)101438-2-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-2-a | 783-08-4 | (NZ)-4-Methoxy-N-(phenylmethylidene)aniline |
| (II)101438-2-a | 13831-31-7 | (2-Chloranyl-2-oxidanylideneethyl) ethanoate |
| (III)101438-2-a | 146924-90-5 | cis-1-(4-Methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl acetate |
| (IV)101438-2-a | 144790-01-2 | cis-2-Oxo-4-phenylazetidin-3-yl acetate |
| (IX)101438-2-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (VI)101438-2-a | 132127-34-5 | (3R,4S)-3-hydroxy-4-phenylazetidin-2-one |
| (VII)101438-2-a | 109-92-2 | [(Ethenyl)oxy]ethane |
| (VIII)101438-2-a | 201856-48-6 | (3R,4S)-3-(1-Ethoxyethoxy)-4-phenylazetidin-2-one |
| (X)101438-2-a | 201856-53-3 | 1-Benzoyl-3(R)-(1-ethoxyethoxy)-4(S)-phenylazetidin-2-one |
| (XI)101438-2-a | 216094-54-1 | 3(S)-(Benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropionic acid |
| (XII)101438-2-a | 182072-57-7 | (4S,5R)-5-(1-ethoxyethoxy)-2,4-diphenyl-5,6-dihydro-4H-1,3-oxazin-6-one |
| (XIII)101438-2-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XIV)101438-2-a | - | (1S,2S,3R,4S,7R,9R,10S,12R,15S)-4,12-bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 4Steps 2 · Total yield /
(I)101438-3-a90332-63-1(II)101438-3-a78432-77-6(III)101438-3-a92950-40-8API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-3-a | 90332-63-1 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy]-1,10-dihydroxy-9-oxo-7-(beta-D-xylopyranosyloxy)-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-3-a | 78432-77-6 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy]-1,7,10-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-3-a | 92950-40-8 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-2-(acetyloxy)-3-benzamido-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 5Steps 9 · Total yield /
(I)101438-4-a3132-99-8(II)101438-4-a104-94-9(III)101438-4-a—(IV)101438-4-a13831-31-7(IX)101438-4-a98-88-4(V)101438-4-a673855-69-1(VI)101438-4-a—(VII)101438-4-a—(VIII)101438-4-a—(X)101438-4-a—(XI)101438-4-a115437-21-3(XII)101438-4-a27548-93-2(XIII)101438-4-a—(XIV)101438-4-a—(XV)101438-4-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-4-a | 3132-99-8 | (3-Bromophenyl)formaldehyde |
| (II)101438-4-a | 104-94-9 | 1-Amino-4-methoxybenzene |
| (III)101438-4-a | - | (NZ)-N-[(3-bromophenyl)methylidene]-4-methoxyaniline |
| (IV)101438-4-a | 13831-31-7 | (2-Chloranyl-2-oxidanylideneethyl) ethanoate |
| (IX)101438-4-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (V)101438-4-a | 673855-69-1 | (2S,3R)-2-(3-bromophenyl)-1-(4-methoxyphenyl)-4-oxoazetidin-3-yl acetate |
| (VI)101438-4-a | - | (2S,3R)-2-(3-bromophenyl)-4-oxoazetidin-3-yl acetate |
| (VII)101438-4-a | - | (3R,4S)-4-(3-bromophenyl)-3-hydroxyazetidin-2-one |
| (VIII)101438-4-a | - | (3R,4S)-4-(3-bromophenyl)-3-[(triethylsilyl)oxy]azetidin-2-one |
| (X)101438-4-a | - | (3R,4S)-1-benzoyl-4-(3-bromophenyl)-3-[(triethylsilyl)oxy]azetidin-2-one |
| (XI)101438-4-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XII)101438-4-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XIII)101438-4-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-(3-bromophenyl)-3-(phenylformamido)-2-[(triethylsilyl)oxy]propanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XIV)101438-4-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-(3-bromophenyl)-2-hydroxy-3-(phenylformamido)propanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XV)101438-4-a | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-(3-tritiophenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 6Steps 9 · Total yield /
(I)101438-5-a34281-92-0(II)101438-5-a19810-31-2(III)101438-5-a—(IV)101438-5-a144666-36-4(IX)101438-5-a132127-34-5(V)101438-5-a132201-30-0(VI)101438-5-a17599-61-0(VII)101438-5-a100-52-7(VIII)101438-5-a132127-31-2(X)101438-5-a201856-48-6(XI)101438-5-a98-88-4(XII)101438-5-a201856-53-3(XIII)101438-5-a115437-21-3(XIV)101438-5-a115437-19-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-5-a | 34281-92-0 | (1S,2R)-2-phenylcyclohexan-1-ol |
| (II)101438-5-a | 19810-31-2 | 2-(Benzyloxy)acetyl chloride |
| (III)101438-5-a | - | (1S,2R)-2-phenylcyclohexyl 2-(benzyloxy)acetate |
| (IV)101438-5-a | 144666-36-4 | (1S,2R)-2-phenylcyclohexyl 2-hydroxyacetate |
| (IX)101438-5-a | 132127-34-5 | (3R,4S)-3-hydroxy-4-phenylazetidin-2-one |
| (V)101438-5-a | 132201-30-0 | (1S,2R)-2-phenylcyclohexyl 2-[(triisopropylsilyl)oxy]acetate |
| (VI)101438-5-a | 17599-61-0 | 1,1,1-Trimethyl-N-[(E)-phenylmethylidene]silanamine |
| (VII)101438-5-a | 100-52-7Available | Benzaldehyde |
| (VIII)101438-5-a | 132127-31-2 | (3R,4S)-4-Phenyl-3-{[tris(propan-2-yl)silyl]oxy}azetidin-2-one |
| (X)101438-5-a | 201856-48-6 | (3R,4S)-3-(1-Ethoxyethoxy)-4-phenylazetidin-2-one |
| (XI)101438-5-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (XII)101438-5-a | 201856-53-3 | 1-Benzoyl-3(R)-(1-ethoxyethoxy)-4(S)-phenylazetidin-2-one |
| (XIII)101438-5-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XIV)101438-5-a | 115437-19-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 7Steps 4 · Total yield /
(I)101438-6-a—(II)101438-6-a17599-61-0(III)101438-6-a132127-30-1(IV)101438-6-a156413-60-4(V)101438-6-a115437-21-3(VI)101438-6-a156413-61-5API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-6-a | - | 1-[(dicyclohexylsulfamoyl)methyl]-7,7-dimethylbicyclo[2.2.1]heptan-2-yl 2-[(tert-butyldimethylsilyl)oxy]acetate |
| (II)101438-6-a | 17599-61-0 | 1,1,1-Trimethyl-N-[(E)-phenylmethylidene]silanamine |
| (III)101438-6-a | 132127-30-1 | (3R,4S)-3-[[tert-Butyl(dimethyl)silyl]oxy]-4-phenylazetidin-2-one |
| (IV)101438-6-a | 156413-60-4 | (3R,4S)-1-benzoyl-3-[(tert-butyldimethylsilyl)oxy]-4-phenylazetidin-2-one |
| (V)101438-6-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VI)101438-6-a | 156413-61-5 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-[(tert-butyldimethylsilyl)oxy]-3-phenyl-3-(phenylformamido)propanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 8Steps 13 · Total yield /
(I)101438-7-a—(II)101438-7-a—(III)101438-7-a—(IV)101438-7-a—(IX)101438-7-a—(V)101438-7-a—(VI)101438-7-a—(VII)101438-7-a—(VIII)101438-7-a—(X)101438-7-a—(XI)101438-7-a—(XII)101438-7-a—(XIII)101438-7-a—(XIV)101438-7-a—(XV)101438-7-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-7-a | - | ethyl (3aR,4S,5S,7aS)-5,7a-dihydroxy-4-methyl-1-oxo-1,3,3a,4,5,7a-hexahydro-2-benzofuran-4-carboxylate |
| (II)101438-7-a | - | (3aR,4R,5S,7aS)-5,7a-bis[(tert-butyldimethylsilyl)oxy]-4-(hydroxymethyl)-4-methyl-1,3,3a,4,5,7a-hexahydro-2-benzofuran-1-one |
| (III)101438-7-a | - | (3aR,4R,5S,7aS)-7a-[(tert-butyldimethylsilyl)oxy]-4-{[(tert-butyldimethylsilyl)oxy]methyl}-5-hydroxy-4-methyl-1,3,3a,4,5,7a-hexahydro-2-benzofuran-1-one |
| (IV)101438-7-a | - | (1S,4S,5R,6R)-5-{[(tert-butyldimethylsilyl)oxy]methyl}-1,6-bis(hydroxymethyl)-5-methylcyclohex-2-ene-1,4-diol |
| (IX)101438-7-a | - | (5S,8S,9R,10R)-9-{[(tert-butyldimethylsilyl)oxy]methyl}-10-[(S)-hydroxy[(1S,6S)-3-(hydroxymethyl)-2,2,4-trimethyl-7-oxabicyclo[4.1.0]hept-3-en-1-yl]methyl]-2,2,9-trimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-ol |
| (V)101438-7-a | - | (5S,8S,9R,10R)-9-{[(tert-butyldimethylsilyl)oxy]methyl}-10-(hydroxymethyl)-2,2,9-trimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-ol |
| (VI)101438-7-a | - | (5S,6S,7R,8S)-7-{[(tert-butyldimethylsilyl)oxy]methyl}-8-hydroxy-2,2,7-trimethyl-1,3-dioxaspiro[4.5]dec-9-ene-6-carbaldehyde |
| (VII)101438-7-a | - | N'-[(1Z)-3-{[(tert-butyldimethylsilyl)oxy]methyl}-2,2,4-trimethylcyclohex-3-en-1-ylidene]-2,4,6-triisopropylbenzenesulfonohydrazide |
| (VIII)101438-7-a | - | (5S,8S,9R,10R)-9-{[(tert-butyldimethylsilyl)oxy]methyl}-10-[(S)-hydroxy[5-(hydroxymethyl)-4,6,6-trimethylcyclohexa-1,4-dien-1-yl]methyl]-2,2,9-trimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-ol |
| (X)101438-7-a | - | (5S,8S,9R,10R)-9-{[(tert-butyldimethylsilyl)oxy]methyl}-10-[(S)-hydroxy[(1S)-1-hydroxy-3-(hydroxymethyl)-2,2,4-trimethylcyclohex-3-en-1-yl]methyl]-2,2,9-trimethyl-1,3-dioxaspiro[4.5]dec-6-en-8-ol |
| (XI)101438-7-a | - | (4S,5S)-4-[(5S,6R,7R,8S)-7-{[(tert-butyldimethylsilyl)oxy]methyl}-8-hydroxy-2,2,7-trimethyl-1,3-dioxaspiro[4.5]dec-9-en-6-yl]-7-(hydroxymethyl)-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
| (XII)101438-7-a | - | (5S,6R,7S,8S)-8-hydroxy-6-[(4S,5S)-7-(hydroxymethyl)-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-4-yl]-2,2,7-trimethyl-1,3-dioxaspiro[4.5]dec-9-ene-7-carbaldehyde |
| (XIII)101438-7-a | - | (1'S,2S,5'S,6'R,10'S,11'S,12'S,13'R)-10',12',13'-trihydroxy-5,5,11',15',18',18'-hexamethyl-2',4'-dioxaspiro[1,4-dioxolane-2,7'-tetracyclo[12.3.1.0(1,5).0(6,11)]octadecane]-8',14'-dien-3'-one |
| (XIV)101438-7-a | - | (1'S,2S,5'S,6'R,10'S,11'S,13'R)-10'-hydroxy-5,5,11',15',18',18'-hexamethyl-3',12'-dioxo-2',4'-dioxaspiro[1,4-dioxolane-2,7'-tetracyclo[12.3.1.0(1,5).0(6,11)]octadecane]-8',14'-dien-13'-yl acetate |
| (XV)101438-7-a | - | (1S,5S,6R,7S,8S,10S,11S,13R)-7,8,10-trihydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3,12-dioxo-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
OptimisedRoute 9Steps 4 · Total yield /
(XIX)101438-7-b155588-15-1(XV)101438-7-b—(XVI)101438-7-b162088-60-0(XVII)101438-7-b—(XVIII)101438-7-b162238-76-8(XX)101438-7-b155588-13-9(XXI)101438-7-b150665-56-8(XXII)101438-7-b115437-21-3(XXIII)101438-7-b149249-91-2(XXIV)101438-7-b135365-62-7API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIX)101438-7-b | 155588-15-1 | (1S,5S,6R,7S,10R,12S,13S,15R)-15-(acetyloxy)-13,17,20,20-tetramethyl-3,14-dioxo-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
| (XV)101438-7-b | - | (1S,5S,6R,7S,8S,10S,11S,13R)-7,8,10-trihydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3,12-dioxo-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
| (XVI)101438-7-b | 162088-60-0 | [(1S,5S,6R,7S,8S,10S,11S,13R)-13-(acetyloxy)-7,8,10-trihydroxy-11,15,18,18-tetramethyl-3,12-dioxo-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-7-yl]methyl acetate |
| (XVII)101438-7-b | - | (1S,5S,6R,7S,8S,10S,11S,13R)-7,8-dihydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
| (XVIII)101438-7-b | 162238-76-8 | (1S,5S,6R,7S,10R,12S,13S,15R)-7-hydroxy-13,17,20,20-tetramethyl-3,14-dioxo-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XX)101438-7-b | 155588-13-9 | (1S,2S,3R,4S,7R,9S,10S,12R)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXI)101438-7-b | 150665-56-8 | (1S,2S,3R,4S,7R,9S,10S,12R)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11,15-dioxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXII)101438-7-b | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXIII)101438-7-b | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (XXIV)101438-7-b | 135365-62-7 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 10Steps 4 · Total yield /
(I)101438-8-a32981-86-5(II)101438-8-a115437-18-8(III)101438-8-a115437-21-3(IV)101438-8-a216094-54-1(V)101438-8-a115437-19-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-8-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-8-a | 115437-18-8 | (2alpha,5beta,7beta,10beta,13alpha)-4-Acetoxy-1,10,13-trihydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-8-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-8-a | 216094-54-1 | 3(S)-(Benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropionic acid |
| (V)101438-8-a | 115437-19-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 11Steps 2 · Total yield /
(I)101438-9-a201856-53-3(II)101438-9-a115437-21-3(III)101438-9-a115437-19-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-9-a | 201856-53-3 | 1-Benzoyl-3(R)-(1-ethoxyethoxy)-4(S)-phenylazetidin-2-one |
| (II)101438-9-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-9-a | 115437-19-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 12Steps 11 · Total yield /
(I)101438-10-a142722-84-7(II)101438-10-a100-52-7(III)101438-10-a144704-63-2(IV)101438-10-a126060-73-9(IX)101438-10-a143527-70-2(V)101438-10-a144787-20-2(VI)101438-10-a143615-00-3(VII)101438-10-a143527-75-7(VIII)101438-10-a143527-74-6(X)101438-10-a103150-33-0(XI)101438-10-a143527-73-5(XII)101438-10-a114915-15-0(XIII)101438-10-a114915-17-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-10-a | 142722-84-7 | (4S,5R)-3-(2-bromoacetyl)-4-methyl-5-phenyl-1,3-oxazolidin-2-one |
| (II)101438-10-a | 100-52-7Available | Benzaldehyde |
| (III)101438-10-a | 144704-63-2 | (4S,5R)-3-[(2S,3R)-2-bromo-3-hydroxy-3-phenylpropanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one |
| (IV)101438-10-a | 126060-73-9 | Ethyl (2R,3R)-3-phenyloxirane-2-carboxylate |
| (IX)101438-10-a | 143527-70-2 | (4S,5R)-3-(tert-Butoxycarbonyl)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (V)101438-10-a | 144787-20-2 | Ethyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate |
| (VI)101438-10-a | 143615-00-3 | Ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate |
| (VII)101438-10-a | 143527-75-7 | Ethyl (2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoate |
| (VIII)101438-10-a | 143527-74-6 | 3-tert-butyl 5-ethyl (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (X)101438-10-a | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XI)101438-10-a | 143527-73-5 | 5-(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl 3-tert-butyl (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (XII)101438-10-a | 114915-15-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XIII)101438-10-a | 114915-17-2 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 13Steps 14 · Total yield /
(I)101438-11-a—(II)101438-11-a—(III)101438-11-a—(IV)101438-11-a2100-17-6(IX)101438-11-a153145-21-2(V)101438-11-a153145-11-0(VI)101438-11-a—(VII)101438-11-a1246643-72-0(VIII)101438-11-a—(X)101438-11-a—(XI)101438-11-a—(XII)101438-11-a153145-16-5(XIII)101438-11-a—(trans-XIV)101438-11-a153221-22-8(cis-XIV)101438-11-a153145-17-6(trans-XV)101438-11-a153221-23-9(cis-XV)101438-11-a153145-18-7(XVI)101438-11-a153145-19-8(XVII)101438-11-a,(XVII)101438-11-b153145-20-1API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-11-a | - | (2R,4R,5S)-4,10,11,11-tetramethyltricyclo[5.3.1.0(1,5)]undec-9-ene-2,5-diol |
| (II)101438-11-a | - | (2R,4R,5S)-4,10,11,11-tetramethyl-2-[(triethylsilyl)oxy]tricyclo[5.3.1.0(1,5)]undec-9-en-5-ol |
| (III)101438-11-a | - | (1R,4R,6R,9S)-9-[(tert-butyldimethylsilyl)oxy]-4,8,11,11-tetramethyl-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-3-one |
| (IV)101438-11-a | 2100-17-6 | 4-Pentenal |
| (IX)101438-11-a | 153145-21-2 | (1S,2R,3S,4R,6R,9S)-9-[(tert-butyldimethylsilyl)oxy]-4-[(1S)-1-hydroxypent-4-en-1-yl]-4,8,11,11-tetramethyl-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-ene-2,3-diol |
| (V)101438-11-a | 153145-11-0 | (1R,4R,6R,9S)-9-[(tert-butyldimethylsilyl)oxy]-4-[(1S)-1-hydroxypent-4-en-1-yl]-4,8,11,11-tetramethyl-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-3-one |
| (VI)101438-11-a | - | (1S)-1-[(1R,4R,6R,9S)-9-[(tert-butyldimethylsilyl)oxy]-4,8,11,11-tetramethyl-3-oxo-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-4-yl]pent-4-en-1-yl propanoate |
| (VII)101438-11-a | 1246643-72-0 | 7,7-dimethyl-1-[(oxaziridine-2-sulfonyl)methyl]bicyclo[2.2.1]heptan-2-one |
| (VIII)101438-11-a | - | (1S)-1-[(1S,2R,4R,6R,9S)-9-[(tert-butyldimethylsilyl)oxy]-2-hydroxy-4,8,11,11-tetramethyl-3-oxo-6-[(triethylsilyl)oxy]bicyclo[5.3.1]undec-7-en-4-yl]pent-4-en-1-yl propanoate |
| (X)101438-11-a | - | (1S,2R,3S,7S,8R,10R,13S)-7-(but-3-en-1-yl)-13-[(tert-butyldimethylsilyl)oxy]-2-hydroxy-8,12,15,15-tetramethyl-10-[(triethylsilyl)oxy]-4,6-dioxatricyclo[9.3.1.0(3,8)]pentadec-11-en-5-one |
| (XI)101438-11-a | - | (1S,3S,7S,8R,10R,13S)-7-(but-3-en-1-yl)-13-[(tert-butyldimethylsilyl)oxy]-8,12,15,15-tetramethyl-10-[(triethylsilyl)oxy]-4,6-dioxatricyclo[9.3.1.0(3,8)]pentadec-11-ene-2,5-dione |
| (XII)101438-11-a | 153145-16-5 | (1S,3S,6S,7R,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-3-hydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione |
| (XIII)101438-11-a | - | (1S,6S,7S,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-2-hydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradeca-2,10-dien-4-one |
| (trans-XIV)101438-11-a | 153221-22-8 | (1S,3R,6S,7S,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione |
| (cis-XIV)101438-11-a | 153145-17-6 | (1S,3S,6S,7S,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione |
| (trans-XV)101438-11-a | 153221-23-9 | (1S,3R,6S,7S,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione |
| (cis-XV)101438-11-a | 153145-18-7 | (1S,3S,6S,7S,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-ene-2,4-dione |
| (XVI)101438-11-a | 153145-19-8 | (1S,2S,3R,6S,7S,9R,12S)-6-(but-3-en-1-yl)-12-[(tert-butyldimethylsilyl)oxy]-1,2-dihydroxy-7,11,14,14-tetramethyl-9-[(triethylsilyl)oxy]-5-oxatricyclo[8.3.1.0(3,7)]tetradec-10-en-4-one |
| (XVII)101438-11-a,(XVII)101438-11-b | 153145-20-1 | (1S,5S,6R,9S,10S,12R,15S)-9-(but-3-en-1-yl)-15-[(tert-butyldimethylsilyl)oxy]-10,14,17,17-tetramethyl-12-[(triethylsilyl)oxy]-2,4,8-trioxatetracyclo[11.3.1.0(1,5).0(6,10)]heptadec-13-ene-3,7-dione |
OptimisedRoute 14Steps 14 · Total yield /
(XIX)(XX)101438-11-b153145-23-4,153145-23-4(XVII)101438-11-a,(XVII)101438-11-b153145-20-1(XVIII)101438-11-b153145-22-3(XXI)101438-11-b—(XXII)101438-11-b153145-26-7(XXIII)(XXIV)101438-11-b—(XXIX)101438-11-b—(XXV)101438-11-b—(XXVI)101438-11-b—(XXVII)101438-11-b—(XXVIII)101438-11-b—(XXX)101438-11-b—(XXXI)101438-11-b—(XXXII)101438-11-b,(XXXII)101438-11-c—101438-11-b116-11-0API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIX)(XX)101438-11-b | 153145-23-4,153145-23-4 | methyl (1S,5S,6R,10S,11S,13R,16S)-16-[(tert-butyldimethylsilyl)oxy]-7,10-dihydroxy-11,15,18,18-tetramethyl-3-oxo-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-diene-8-carboxylate |
| (XVII)101438-11-a,(XVII)101438-11-b | 153145-20-1 | (1S,5S,6R,9S,10S,12R,15S)-9-(but-3-en-1-yl)-15-[(tert-butyldimethylsilyl)oxy]-10,14,17,17-tetramethyl-12-[(triethylsilyl)oxy]-2,4,8-trioxatetracyclo[11.3.1.0(1,5).0(6,10)]heptadec-13-ene-3,7-dione |
| (XVIII)101438-11-b | 153145-22-3 | methyl 3-[(1S,5S,6R,9S,10S,12R,15S)-15-[(tert-butyldimethylsilyl)oxy]-10,14,17,17-tetramethyl-3,7-dioxo-12-[(triethylsilyl)oxy]-2,4,8-trioxatetracyclo[11.3.1.0(1,5).0(6,10)]heptadec-13-en-9-yl]propanoate |
| (XXI)101438-11-b | - | (1S,5S,6R,10S,11S,13R,16S)-16-[(tert-butyldimethylsilyl)oxy]-11,15,18,18-tetramethyl-10-(prop-1-en-2-yloxy)-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-ene-3,7-dione |
| (XXII)101438-11-b | 153145-26-7 | (1S,5S,6R,10S,11S,13R,16S)-16-[(tert-butyldimethylsilyl)oxy]-10-hydroxy-11,15,18,18-tetramethyl-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-ene-3,7-dione |
| (XXIII)(XXIV)101438-11-b | - | (1S,5S,6R,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-11,15,18,18-tetramethyl-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-ene-3,7-dione |
| (XXIX)101438-11-b | - | (1S,5S,6R,7S,8S,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3-oxo-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-8-yl 4-methylbenzene-1-sulfonate |
| (XXV)101438-11-b | - | (1S,5S,6S,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-11,15,18,18-tetramethyl-13-[(triethylsilyl)oxy]-7-[(trimethylsilyl)methyl]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-3-one |
| (XXVI)101438-11-b | - | (1S,5S,6R,8S,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-11,15,18,18-tetramethyl-13-[(triethylsilyl)oxy]-8-[(trimethylsilyl)methyl]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-ene-3,7-dione |
| (XXVII)101438-11-b | - | (3aS,5S,8S,9aR,10S,12S,13aS,13bS)-10-[(Benzyloxy)methyl]-5-[[tert-butyl(dimethyl)silyl]oxy]-12-hydroxy-6,9a,14,14-tetramethyl-13-methylidene-8-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XXVIII)101438-11-b | - | (1S,5S,6R,7S,8S,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3-oxo-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-8-yl methanesulfonate |
| (XXX)101438-11-b | - | (1S,5S,6R,7S,10R,12S,13R,15R,18S)-12-[(benzyloxy)methyl]-18-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-13,17,20,20-tetramethyl-15-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-3-one |
| (XXXI)101438-11-b | - | (1S,5S,6R,7S,10R,12S,13R,15R,18S)-12-[(benzyloxy)methyl]-18-[(tert-butyldimethylsilyl)oxy]-13,17,20,20-tetramethyl-3-oxo-15-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
| (XXXII)101438-11-b,(XXXII)101438-11-c | - | (1S,5S,6R,7S,10R,12S,13R,15R,18S)-12-[(benzyloxy)methyl]-18-[(tert-butyldimethylsilyl)oxy]-15-hydroxy-13,17,20,20-tetramethyl-3-oxo-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
| 101438-11-b | 116-11-0 | 2-Methoxy-1-propene |
OptimisedRoute 15Steps 6 · Total yield /
(XXXII)101438-11-b,(XXXII)101438-11-c—(XXXIII)101438-11-c—(XXXIV)101438-11-c—(XXXV)101438-11-c—(XXXVI)101438-11-c—(XXXVII)101438-11-c149249-91-2(XXXVIII)101438-11-c—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXXII)101438-11-b,(XXXII)101438-11-c | - | (1S,5S,6R,7S,10R,12S,13R,15R,18S)-12-[(benzyloxy)methyl]-18-[(tert-butyldimethylsilyl)oxy]-15-hydroxy-13,17,20,20-tetramethyl-3-oxo-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
| (XXXIII)101438-11-c | - | (1S,2S,3R,4S,7R,9S,10R,15S)-4-(acetyloxy)-9-[(benzyloxy)methyl]-15-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-12-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXXIV)101438-11-c | - | potassium (1S,2S,3R,4S,7R,9S,10S,11E,15S)-4-(acetyloxy)-2-(benzoyloxy)-9-[(benzyloxy)methyl]-15-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadeca-11,13-dien-12-olate |
| (XXXV)101438-11-c | - | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetyloxy)-9-[(benzyloxy)methyl]-15-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXXVI)101438-11-c | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-7-[(benzyloxy)methyl]-1,13-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XXXVII)101438-11-c | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (XXXVIII)101438-11-c | - | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetyloxy)-9-[(benzyloxy)methyl]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-{[(2R,3S)-3-phenyl-3-(phenylformamido)-2-[(triethylsilyl)oxy]propanoyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 16Steps 8 · Total yield /
(VIIIa)101438-13-a149140-54-5(III)101438-13-a783-08-4(II)101438-13-a104-94-9(Xb)101438-13-a201856-53-3(IX)101438-13-a98-88-4(I)101438-13-a100-52-7(V)101438-13-a146924-90-5(VI)101438-13-a144790-01-2(Xa)101438-13-a149249-91-2(VIIIb)101438-13-a201856-48-6(VII)101438-13-a132127-34-5(XI)101438-13-a,(XI)101438-13-c115437-21-3(IV)101438-13-a13831-31-7(XIIa)101438-13-a135365-62-7(XIIb)101438-13-a115437-19-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (VIIIa)101438-13-a | 149140-54-5 | (3R,4S)-4-Phenyl-3-[(triethylsilyl)oxy]azetidin-2-one |
| (III)101438-13-a | 783-08-4 | (NZ)-4-Methoxy-N-(phenylmethylidene)aniline |
| (II)101438-13-a | 104-94-9 | 1-Amino-4-methoxybenzene |
| (Xb)101438-13-a | 201856-53-3 | 1-Benzoyl-3(R)-(1-ethoxyethoxy)-4(S)-phenylazetidin-2-one |
| (IX)101438-13-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (I)101438-13-a | 100-52-7Available | Benzaldehyde |
| (V)101438-13-a | 146924-90-5 | cis-1-(4-Methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl acetate |
| (VI)101438-13-a | 144790-01-2 | cis-2-Oxo-4-phenylazetidin-3-yl acetate |
| (Xa)101438-13-a | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (VIIIb)101438-13-a | 201856-48-6 | (3R,4S)-3-(1-Ethoxyethoxy)-4-phenylazetidin-2-one |
| (VII)101438-13-a | 132127-34-5 | (3R,4S)-3-hydroxy-4-phenylazetidin-2-one |
| (XI)101438-13-a,(XI)101438-13-c | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-13-a | 13831-31-7 | (2-Chloranyl-2-oxidanylideneethyl) ethanoate |
| (XIIa)101438-13-a | 135365-62-7 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XIIb)101438-13-a | 115437-19-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 17Steps 9 · Total yield /
(XIII)101438-13-b—(XIV)101438-13-b530-62-1(XIX)101438-13-b—(XV)101438-13-b—(XVI)101438-13-b—(XVII)101438-13-b—(XVIII)101438-13-b1782958-99-9(XX)101438-13-b—(XXI)101438-13-b—(XXII)101438-13-b1782959-00-5(XXIII)101438-13-b,(XXIII)101438-13-c1782958-86-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIII)101438-13-b | - | (2alpha,5beta,7beta,10beta)-1,2,7,10-Tetrahydroxytaxa-4(20),11-dien-5-yl acetate |
| (XIV)101438-13-b | 530-62-1 | 1-[(1H-Imidazol-1-yl)carbonyl]1H-imidazole |
| (XIX)101438-13-b | - | (3aS,9aS,10S,12R,13S,13aR,13bS)-12,13-Dihydroxy-13-(hydroxymethyl)-6,9a,14,14-tetramethyl-10-[(triethylsilyl)oxy]-9,9a,10,11,12,13,13a,13b-octahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8(5H)-dione |
| (XV)101438-13-b | - | (3aS,8S,9aS,10S,12R,13aR,13bS)-8,10-Dihydroxy-6,9a,14,14-tetramethyl-13-methylene-2-oxo-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-12-yl acetate |
| (XVI)101438-13-b | - | (3aS,8S,9aS,10S,12R,13aR,13bS)-8-Hydroxy-6,9a,14,14-tetramethyl-13-methylene-2-oxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-12-yl acetate |
| (XVII)101438-13-b | - | (3aS,9aS,10S,12R,13aR,13bS)-6,9a,14,14-Tetramethyl-13-methylene-2,8-dioxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-12-yl acetate |
| (XVIII)101438-13-b | 1782958-99-9 | (3aS,9aS,10S,12S,13aR,13bS)-12-Hydroxy-6,9a,14,14-tetramethyl-13-methylene-10-[(triethylsilyl)oxy]-9,9a,10,11,12,13,13a,13b-octahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8(5H)-dione |
| (XX)101438-13-b | - | [(3aS,9aS,10S,12R,13S,13aR,13bS)-12,13-Dihydroxy-6,9a,14,14-tetramethyl-2,8-dioxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-13-yl]methyl acetate |
| (XXI)101438-13-b | - | [(3aS,9aS,10S,12R,13S,13aR,13bS)-13-Hydroxy-6,9a,14,14-tetramethyl-12-[(methylsulfonyl)oxy]-2,8-dioxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-13-yl]methyl acetate |
| (XXII)101438-13-b | 1782959-00-5 | (3aS,9aS,10S,12S,13S,13aR,13bS)-13-Hydroxy-13-(hydroxymethyl)-6,9a,14,14-tetramethyl-2,8-dioxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-12-yl methanesulfonate |
| (XXIII)101438-13-b,(XXIII)101438-13-c | 1782958-86-4 | (3aS,9aS,10S,11aR,13aS,13bR,13cS)-13a-Hydroxy-6,9a,14,14-tetramethyl-10-[(triethylsilyl)oxy]-4,5,9a,10,11,11a,13,13a,13b,13c-decahydro-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxete-2,8(9H)-dione |
OptimisedRoute 18Steps 5 · Total yield /
(XI)101438-13-a,(XI)101438-13-c115437-21-3(XXIII)101438-13-b,(XXIII)101438-13-c1782958-86-4(XXIV)101438-13-c108-24-7(XXIX)101438-13-c—(XXV)101438-13-c—(XXVI)101438-13-c—(XXVII)101438-13-c168421-81-6(XXVIII)101438-13-c—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XI)101438-13-a,(XI)101438-13-c | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXIII)101438-13-b,(XXIII)101438-13-c | 1782958-86-4 | (3aS,9aS,10S,11aR,13aS,13bR,13cS)-13a-Hydroxy-6,9a,14,14-tetramethyl-10-[(triethylsilyl)oxy]-4,5,9a,10,11,11a,13,13a,13b,13c-decahydro-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxete-2,8(9H)-dione |
| (XXIV)101438-13-c | 108-24-7 | Acetic acid acetic anhydride |
| (XXIX)101438-13-c | - | (2alpha,5beta,7beta,9beta,10beta)-4,10-Diacetoxy-1,9-dihydroxy-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XXV)101438-13-c | - | (3aS,9aS,10S,11aR,13aS,13bR,13cS)-6,9a,14,14-Tetramethyl-2,8-dioxo-10-[(triethylsilyl)oxy]-4,5,8,9,9a,10,11,11a,13b,13c-decahydro-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxet-13a(13H)-yl acetate |
| (XXVI)101438-13-c | - | Lithiumbenzene |
| (XXVII)101438-13-c | 168421-81-6 | (2alpha,5beta,7beta)-4-Acetoxy-1-hydroxy-10-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XXVIII)101438-13-c | - | (2alpha,5beta,7beta,9beta)-4-Acetoxy-1,9-dihydroxy-10-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 19Steps 6 · Total yield /
(I)101438-14-a94594-90-8(II)101438-14-a155396-72-8(III)101438-14-a—(IV)101438-14-a—(IX)101438-14-a157826-11-4(V)101438-14-a—(VI)101438-14-a—(VII)101438-14-a949023-16-9(VIII)101438-14-a115437-21-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-14-a | 94594-90-8 | (3aS)-8,8-Dimethylhexahydro-3a,6-methano-2lambda6-2lambda6,1-benzothiazole-2,2(3H)-dione |
| (II)101438-14-a | 155396-72-8 | 2-((4-methoxybenzyl)oxy)acetyl chloride |
| (III)101438-14-a | - | (1S,5S,7R)-4-{2-[(4-methoxyphenyl)methoxy]acetyl}-10,10-dimethyl-3-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione |
| (IV)101438-14-a | - | N-[(1Z)-Phenylmethylidene]benzamide |
| (IX)101438-14-a | 157826-11-4 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (2R,4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate |
| (V)101438-14-a | - | N-[(1S,2R)-3-[(1S,5S,7R)-10,10-dimethyl-3,3-dioxo-3-thia-4-azatricyclo[5.2.1.0(1,5)]decan-4-yl]-2-[(4-methoxyphenyl)methoxy]-3-oxo-1-phenylpropyl]benzamide |
| (VI)101438-14-a | - | (1S,5S,7R)-4-{[(4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidin-5-yl]carbonyl}-10,10-dimethyl-3-thia-4-azatricyclo[5.2.1.0(1,5)]decane-3,3-dione |
| (VII)101438-14-a | 949023-16-9 | (4S,5R)-3-Benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (VIII)101438-14-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 20Steps 17 · Total yield /
(I)101438-15-a114198-58-2(II)101438-15-a141665-41-0(IV)(III)101438-15-a141665-43-2,141665-43-2(IX)101438-15-a155619-56-0(V)101438-15-a141665-44-3(VI)101438-15-a141665-48-7(VII)101438-15-a—(VIII)101438-15-a155619-55-9(X)101438-15-a155619-57-1(XI)101438-15-a155619-58-2(XII)101438-15-a152893-54-4(XIII)101438-15-a—(XIV)101438-15-a155619-60-6(XIX)101438-15-a155619-65-1(XV)101438-15-a155619-61-7(XVI)101438-15-a155619-62-8(XVII)101438-15-a—(XVIII)101438-15-a155619-64-0(XX)101438-15-a155619-66-2(XXI)101438-15-a,(XXI)101438-15-b155619-67-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-15-a | 114198-58-2 | 6,6,8-Trimethyl-1,4-dioxaspiro[4.5]decan-7-one |
| (II)101438-15-a | 141665-41-0 | 6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl trifluoromethanesulfonate |
| (IV)(III)101438-15-a | 141665-43-2,141665-43-2 | 7-ethenyl-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-ene |
| (IX)101438-15-a | 155619-56-0 | tert-butyl({[(7S)-9-{2-[(tert-butyldimethylsilyl)oxy]ethyl}-8,10,10-trimethyl-1,4-dioxaspiro[4.5]dec-8-en-7-yl]oxy})dimethylsilane |
| (V)101438-15-a | 141665-44-3 | 2-{6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl}ethan-1-ol |
| (VI)101438-15-a | 141665-48-7 | tert-butyldimethyl(2-{6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl}ethoxy)silane |
| (VII)101438-15-a | - | (3aS)-1,3,3-trimethyl-hexahydropyrrolo[1,2-c][1,3,2]oxazaborole |
| (VIII)101438-15-a | 155619-55-9 | (7S)-9-{2-[(tert-butyldimethylsilyl)oxy]ethyl}-8,10,10-trimethyl-1,4-dioxaspiro[4.5]dec-8-en-7-ol |
| (X)101438-15-a | 155619-57-1 | 2-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]ethan-1-ol |
| (XI)101438-15-a | 155619-58-2 | 2-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]acetaldehyde |
| (XII)101438-15-a | 152893-54-4 | tert-butyl({[(2E)-3-iodobut-2-en-1-yl]oxy})dimethylsilane |
| (XIII)101438-15-a | - | (3E)-4-[(tert-butyldimethylsilyl)oxy]-1-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]-3-methylbut-3-en-2-ol |
| (XIV)101438-15-a | 155619-60-6 | (3E)-5-[(tert-butyldimethylsilyl)oxy]-1-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]-3-methylpent-3-en-2-one |
| (XIX)101438-15-a | 155619-65-1 | 1-[(1S,2R,3S,6S)-6-(benzyloxy)-2-(hydroxymethyl)-1-methyl-4-oxo-3-[(phenylsulfanyl)methyl]cyclohexyl]-2-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]ethane-1,2-dione |
| (XV)101438-15-a | 155619-61-7 | (3E)-5-[(tert-butyldimethylsilyl)oxy]-1-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]-1-hydroxy-3-methylpent-3-en-2-one |
| (XVI)101438-15-a | 155619-62-8 | (3E)-5-[(tert-butyldimethylsilyl)oxy]-1-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]-3-methylpent-3-ene-1,2-dione |
| (XVII)101438-15-a | - | [(2Z,3E)-4-(benzyloxy)-2-[2-(phenylsulfanyl)ethylidene]but-3-en-1-yl]trimethylsilane |
| (XVIII)101438-15-a | 155619-64-0 | 1-[(1S,2R,3S,6S)-6-(benzyloxy)-2-{[(tert-butyldimethylsilyl)oxy]methyl}-1-methyl-4-oxo-3-[(phenylsulfanyl)methyl]cyclohexyl]-2-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]ethane-1,2-dione |
| (XX)101438-15-a | 155619-66-2 | (1R,2S,3S,6S)-3-(benzyloxy)-2-{2-[(9S)-9-[(tert-butyldimethylsilyl)oxy]-6,6,8-trimethyl-1,4-dioxaspiro[4.5]dec-7-en-7-yl]-2-oxoacetyl}-2-methyl-5-oxo-6-[(phenylsulfanyl)methyl]cyclohexane-1-carbaldehyde |
| (XXI)101438-15-a,(XXI)101438-15-b | 155619-67-3 | (1R,2S,3S,6S)-3-(benzyloxy)-2-{2-[(3S)-3-hydroxy-2,6,6-trimethyl-5-oxocyclohex-1-en-1-yl]-2-oxoacetyl}-2-methyl-5-oxo-6-[(phenylsulfanyl)methyl]cyclohexane-1-carbaldehyde |
OptimisedRoute 21Steps 10 · Total yield /
(XXI)101438-15-a,(XXI)101438-15-b155619-67-3(XXII)101438-15-b—(XXIII)101438-15-b—(XXIV)101438-15-b155619-70-8(XXIX)101438-15-b155619-75-3(XXV)101438-15-b155619-71-9(XXVI)101438-15-b155619-72-0(XXVII)101438-15-b—(XXVIII)101438-15-b155619-74-2(XXX)101438-15-b—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXI)101438-15-a,(XXI)101438-15-b | 155619-67-3 | (1R,2S,3S,6S)-3-(benzyloxy)-2-{2-[(3S)-3-hydroxy-2,6,6-trimethyl-5-oxocyclohex-1-en-1-yl]-2-oxoacetyl}-2-methyl-5-oxo-6-[(phenylsulfanyl)methyl]cyclohexane-1-carbaldehyde |
| (XXII)101438-15-b | - | (1S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-1,2,5,10,13-pentahydroxy-8,12,15,15-tetramethyl-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-9-one |
| (XXIII)101438-15-b | - | (1S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-13-[(tert-butyldimethylsilyl)oxy]-1,2,5-trihydroxy-8,12,15,15-tetramethyl-9-oxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-10-yl acetate |
| (XXIV)101438-15-b | 155619-70-8 | (1S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-13-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-8,12,15,15-tetramethyl-2,5,9-trioxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-10-yl acetate |
| (XXIX)101438-15-b | 155619-75-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-bis(benzyloxy)-15-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXV)101438-15-b | 155619-71-9 | (1S,2S,3R,4S,7S,8S,10R,13S)-7-(benzyloxy)-13-[(tert-butyldimethylsilyl)oxy]-1,2-dihydroxy-8,12,15,15-tetramethyl-5,9-dioxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-10-yl acetate |
| (XXVI)101438-15-b | 155619-72-0 | (1S,2S,3R,4S,7S,8S,10R,13S)-10-(acetyloxy)-1,7-bis(benzyloxy)-13-[(tert-butyldimethylsilyl)oxy]-8,12,15,15-tetramethyl-5,9-dioxo-4-[(phenylsulfanyl)methyl]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXVII)101438-15-b | - | (1S,2S,3R,4S,5R,7S,8S,10R,13S)-10-(acetyloxy)-1,7-bis(benzyloxy)-13-[(tert-butyldimethylsilyl)oxy]-4,5-dihydroxy-4-(hydroxymethyl)-8,12,15,15-tetramethyl-9-oxotricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXVIII)101438-15-b | 155619-74-2 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-1,9-bis(benzyloxy)-15-[(tert-butyldimethylsilyl)oxy]-4-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXX)101438-15-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-bis(benzyloxy)-15-{[(2R,3S)-2-(2-ethoxyethoxy)-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 22Steps 16 · Total yield /
(I)101438-16-a155681-62-2(II)101438-16-a155681-63-3(III)101438-16-a155681-64-4(IV)101438-16-a174589-61-8(IX)101438-16-a155681-71-3(V)101438-16-a155681-65-5(VI)101438-16-a155681-66-6(VII)101438-16-a168038-16-2(VIII)101438-16-a155681-68-8(X)101438-16-a155681-72-4(XI)101438-16-a155681-73-5(XII)101438-16-a155681-61-1(XIII)101438-16-a155619-38-8(XIV)101438-16-a155619-94-6(XIX)101438-16-a,(XIX)101438-16-b155619-42-4(XV)101438-16-a155619-39-9(XVI)101438-16-a155619-40-2(XVII)101438-16-a2130876-10-5(XVIII)101438-16-a155619-41-3101438-16-a107-21-1API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-16-a | 155681-62-2 | (4'aS,5'S)-4'a-methyl-3',4',4'a,5',6',7'-hexahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-5'-ol |
| (II)101438-16-a | 155681-63-3 | [(4'aS,5'S)-4'a-methyl-3',4',4'a,5',6',7'-hexahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-5'-yloxy](tert-butyl)dimethylsilane |
| (III)101438-16-a | 155681-64-4 | (4'aS,5'S,8'aS)-5'-[(tert-butyldimethylsilyl)oxy]-4'a-methyl-octahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-8'-one |
| (IV)101438-16-a | 174589-61-8 | (4'aS,5'S,8'aS)-5'-[(tert-butyldimethylsilyl)oxy]-4'a-methyl-3',4',4'a,5',6',8'a-hexahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-8'-yl trifluoromethanesulfonate |
| (IX)101438-16-a | 155681-71-3 | (1S,2S,5R,7S,8S)-7-[(tert-butyldimethylsilyl)oxy]-2-hydroxy-8-methyl-4-oxatricyclo[6.4.0.0(2,5)]dodecan-11-one |
| (V)101438-16-a | 155681-65-5 | methyl (4'aS,5'S,8'aS)-5'-[(tert-butyldimethylsilyl)oxy]-4'a-methyl-3',4',4'a,5',6',8'a-hexahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-8'-carboxylate |
| (VI)101438-16-a | 155681-66-6 | (4'aS,5'S,8'aR)-5'-[(tert-butyldimethylsilyl)oxy]-4'a-methyl-3',4',4'a,5',6',8'a-hexahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-8'-ylmethanol |
| (VII)101438-16-a | 168038-16-2 | (4'aS,5'S,7'R,8'S,8'aS)-5'-[(tert-butyldimethylsilyl)oxy]-8'-(hydroxymethyl)-4'a-methyl-octahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-7',8'-diol |
| (VIII)101438-16-a | 155681-68-8 | (1'S,2'S,5'R,7'S,8'S)-7'-[(tert-butyldimethylsilyl)oxy]-8'-methyl-4'-oxaspiro[1,3-dioxolane-2,11'-tricyclo[6.4.0.0(2,5)]dodecane]-2'-ol |
| (X)101438-16-a | 155681-72-4 | (1S,2S,5R,7S,8S)-7-[(tert-butyldimethylsilyl)oxy]-2-hydroxy-8-methyl-4-oxatricyclo[6.4.0.0(2,5)]dodec-9-en-11-one |
| (XI)101438-16-a | 155681-73-5 | (1S,2S,5R,7S,8S)-2,7-bis[(tert-butyldimethylsilyl)oxy]-8-methyl-4-oxatricyclo[6.4.0.0(2,5)]dodec-9-en-11-one |
| (XII)101438-16-a | 155681-61-1 | (1S,2S,3S,4S,6R)-1,4-bis[(tert-butyldimethylsilyl)oxy]-3-methyl-7-oxabicyclo[4.2.0]octane-2,3-dicarbaldehyde |
| (XIII)101438-16-a | 155619-38-8 | (1S,2S,3S,4S,6R)-1,4-bis[(tert-butyldimethylsilyl)oxy]-2-(1,3-dioxolan-2-yl)-3-methyl-7-oxabicyclo[4.2.0]octane-3-carbaldehyde |
| (XIV)101438-16-a | 155619-94-6 | [2-(2,4-dimethylpenta-1,3-dien-3-yl)-1,3-dithian-2-yl]lithium |
| (XIX)101438-16-a,(XIX)101438-16-b | 155619-42-4 | (1'S,3'S,4'S,7'R,9'S,10'S)-4',9'-bis[(tert-butyldimethylsilyl)oxy]-1'-(methoxymethoxy)-10',14',17',17'-tetramethyl-6'-oxaspiro[1,3-dithiane-2,12'-tetracyclo[11.3.1.0(3,10).0(4,7)]heptadecan]-13'-ene-2',11'-dione |
| (XV)101438-16-a | 155619-39-9 | tert-butyl({[(1S,2S,3S,4S,6R)-4-[(tert-butyldimethylsilyl)oxy]-3-{[2-(2,4-dimethylpenta-1,3-dien-3-yl)-1,3-dithian-2-yl]carbonyl}-2-(1,3-dioxolan-2-yl)-3-methyl-7-oxabicyclo[4.2.0]octan-1-yl]oxy})dimethylsilane |
| (XVI)101438-16-a | 155619-40-2 | (1S,2S,3S,4S,6R)-1,4-bis[(tert-butyldimethylsilyl)oxy]-3-{[2-(2,4-dimethylpenta-1,3-dien-3-yl)-1,3-dithian-2-yl]carbonyl}-3-methyl-7-oxabicyclo[4.2.0]octane-2-carbaldehyde |
| (XVII)101438-16-a | 2130876-10-5 | 1-lithio-1-(methoxymethoxy)ethene |
| (XVIII)101438-16-a | 155619-41-3 | 1-[(1S,2S,3S,4S,6R)-1,4-bis[(tert-butyldimethylsilyl)oxy]-3-{[2-(2,4-dimethylpenta-1,3-dien-3-yl)-1,3-dithian-2-yl]carbonyl}-3-methyl-7-oxabicyclo[4.2.0]octan-2-yl]-2-(methoxymethoxy)prop-2-en-1-one |
| 101438-16-a | 107-21-1Available | 1,2-Dihydroxyethane |
OptimisedRoute 23Steps 8 · Total yield /
(XIX)101438-16-a,(XIX)101438-16-b155619-42-4(XX)101438-16-b155619-43-5(XXI)101438-16-b155619-44-6(XXII)101438-16-b155619-45-7(XXIII)101438-16-b155619-46-8(XXIV)101438-16-b—(XXV)101438-16-b—(XXVI)101438-16-b—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIX)101438-16-a,(XIX)101438-16-b | 155619-42-4 | (1'S,3'S,4'S,7'R,9'S,10'S)-4',9'-bis[(tert-butyldimethylsilyl)oxy]-1'-(methoxymethoxy)-10',14',17',17'-tetramethyl-6'-oxaspiro[1,3-dithiane-2,12'-tetracyclo[11.3.1.0(3,10).0(4,7)]heptadecan]-13'-ene-2',11'-dione |
| (XX)101438-16-b | 155619-43-5 | (1'S,2'S,3'R,4'S,7'R,9'S,10'S)-4',9'-bis[(tert-butyldimethylsilyl)oxy]-1'-(methoxymethoxy)-10',14',17',17'-tetramethyl-11'-oxo-6'-oxaspiro[1,3-dithiane-2,12'-tetracyclo[11.3.1.0(3,10).0(4,7)]heptadecan]-13'-en-2'-yl benzoate |
| (XXI)101438-16-b | 155619-44-6 | (1'S,2'S,3'R,4'S,7'R,9'S,10'S)-4',9'-bis[(tert-butyldimethylsilyl)oxy]-1'-(methoxymethoxy)-10',14',17',17'-tetramethyl-11',15'-dioxo-6'-oxaspiro[1,3-dithiane-2,12'-tetracyclo[11.3.1.0(3,10).0(4,7)]heptadecan]-13'-en-2'-yl benzoate |
| (XXII)101438-16-b | 155619-45-7 | (1S,2S,3R,4S,7R,9S,10S,15S)-15-(benzyloxy)-4,9-bis[(tert-butyldimethylsilyl)oxy]-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXIII)101438-16-b | 155619-46-8 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetyloxy)-15-(benzyloxy)-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXIV)101438-16-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetyloxy)-15-hydroxy-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXV)101438-16-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetyloxy)-15-{[(2R,3S)-2-(2-ethoxyethoxy)-3-phenyl-3-(phenylformamido)propanoyl]oxy}-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXVI)101438-16-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-(2-ethoxyethoxy)-3-phenyl-3-(phenylformamido)propanoyl]oxy}-9-hydroxy-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 24Steps 12 · Total yield /
(I)101438-17-a39994-75-7(II)101438-17-a148205-41-8(III)101438-17-a14734-27-1(IV)101438-17-a—(IX)101438-17-a165067-86-7(V)101438-17-a13831-31-7(VI)101438-17-a144764-07-8(VII)101438-17-a144764-09-0(VIII)101438-17-a144764-11-4(X)(IX)101438-17-a144764-10-3,144764-10-3(X)101438-17-a165067-87-8(XI)101438-17-a165067-88-9(XII)101438-17-a165067-89-0(XIII)101438-17-a98-88-4(XIV)101438-17-a149249-91-2(XV)101438-17-a115437-21-3(XVI)101438-17-a165067-91-4(XVII)101438-17-a—(XVIII)101438-17-a27548-93-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-17-a | 39994-75-7 | Methyl L-threoninate hydrogen chloride |
| (II)101438-17-a | 148205-41-8 | methyl (2S,3R)-2-amino-3-{[(tert-butoxy)diphenylsilyl]oxy}butanoate |
| (III)101438-17-a | 14734-27-1 | [formyl-[14]C]Benzaldehyde |
| (IV)101438-17-a | - | methyl (2S,3R)-3-[(tert-butyldiphenylsilyl)oxy]-2-[(E)-(phenylmethylidene)amino]butanoate |
| (IX)101438-17-a | 165067-86-7 | methyl 2-[(3S,4S)-3-(acetyloxy)-2-oxo-4-phenylazetidin-1-yl]-2-oxoacetate |
| (V)101438-17-a | 13831-31-7 | (2-Chloranyl-2-oxidanylideneethyl) ethanoate |
| (VI)101438-17-a | 144764-07-8 | methyl (2S,3R)-2-[(3R,4S)-3-(acetyloxy)-2-oxo-4-phenylazetidin-1-yl]-3-[(tert-butyldiphenylsilyl)oxy]butanoate |
| (VII)101438-17-a | 144764-09-0 | methyl (2S,3R)-2-[(3R,4S)-3-(acetyloxy)-2-oxo-4-phenylazetidin-1-yl]-3-hydroxybutanoate |
| (VIII)101438-17-a | 144764-11-4 | methyl (2Z)-2-[(3R,4S)-3-(acetyloxy)-2-oxo-4-phenylazetidin-1-yl]but-2-enoate |
| (X)(IX)101438-17-a | 144764-10-3,144764-10-3 | methyl 2-[(3R,4S)-3-(acetyloxy)-2-oxo-4-phenylazetidin-1-yl]-2-oxoacetate |
| (X)101438-17-a | 165067-87-8 | (3S,4S)-2-oxo-4-phenylazetidin-3-yl acetate |
| (XI)101438-17-a | 165067-88-9 | (3S,4S)-3-hydroxy-4-phenylazetidin-2-one |
| (XII)101438-17-a | 165067-89-0 | (3S,4S)-4-phenyl-3-[(triethylsilyl)oxy]azetidin-2-one |
| (XIII)101438-17-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (XIV)101438-17-a | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (XV)101438-17-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XVI)101438-17-a | 165067-91-4 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-{[(2S,3S)-3-phenyl-3-(phenylformamido)-2-[(triethylsilyl)oxy]propanoyl]oxy}-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XVII)101438-17-a | - | [2aR-(2aalpha,4beta,4abeta,6beta,9alpha(2R,3S),11beta,12alpha,12aalpha,12balpha]-6-Acetoxy-9-[3-(4-deuterobenzamido)-2-hydroxy-3-phenylpropionyloxy]-12-(benzoyloxy)-12b-(trideuteroacetoxy)-4,11-dihydroxy-4a,8,13,13-tetramethyl-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxet- 5-one |
| (XVIII)101438-17-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 25Steps 15 · Total yield /
(I)101438-18-a5073-65-4(II)101438-18-a33878-99-8(III)101438-18-a155681-64-4(IV)101438-18-a155681-66-6(IX)101438-18-a—(V)101438-18-a155681-68-8(VI)101438-18-a168421-83-8(VII)101438-18-a168421-63-4(VIII)101438-18-a—(X)101438-18-a168421-65-6(XI)101438-18-a168421-67-8(XII)101438-18-a168421-68-9(XIII)101438-18-a168421-69-0(XIV)101438-18-a168421-70-3(XV)101438-18-a168421-72-5(XVI)101438-18-a168421-73-6(XVII)101438-18-a168421-75-8(XVIII)101438-18-a,(XVIII)101438-18-b168421-76-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-18-a | 5073-65-4 | 2-Methyl-2-(3-oxobutyl)cyclohexane-1,3-dione |
| (II)101438-18-a | 33878-99-8 | (S)-(+)-3,4,8,8a-Tetrahydro-8a-methyl-1,6(2H,7H)-naphthalenedione |
| (III)101438-18-a | 155681-64-4 | (4'aS,5'S,8'aS)-5'-[(tert-butyldimethylsilyl)oxy]-4'a-methyl-octahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-8'-one |
| (IV)101438-18-a | 155681-66-6 | (4'aS,5'S,8'aR)-5'-[(tert-butyldimethylsilyl)oxy]-4'a-methyl-3',4',4'a,5',6',8'a-hexahydro-1'H-spiro[1,3-dioxolane-2,2'-naphthalene]-8'-ylmethanol |
| (IX)101438-18-a | - | 5-iodo-2,6,6-trimethyl-1-[(trimethylsilyl)methyl]cyclohexa-2,4-diene-1-carbonitrile |
| (V)101438-18-a | 155681-68-8 | (1'S,2'S,5'R,7'S,8'S)-7'-[(tert-butyldimethylsilyl)oxy]-8'-methyl-4'-oxaspiro[1,3-dioxolane-2,11'-tricyclo[6.4.0.0(2,5)]dodecane]-2'-ol |
| (VI)101438-18-a | 168421-83-8 | (1S,2S,5R,7S,8S)-2-(benzyloxy)-7-[(tert-butyldimethylsilyl)oxy]-8-methyl-4-oxatricyclo[6.4.0.0(2,5)]dodecan-11-one |
| (VII)101438-18-a | 168421-63-4 | (1S,2S,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-(2,2-dimethoxyethyl)-3-methyl-7-oxabicyclo[4.2.0]octane-2-carbaldehyde |
| (VIII)101438-18-a | - | 5-lithio-2,6,6-trimethyl-1-[(trimethylsilyl)methyl]cyclohexa-2,4-diene-1-carbonitrile |
| (X)101438-18-a | 168421-65-6 | 5-[(S)-[(1S,2R,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-(2,2-dimethoxyethyl)-3-methyl-7-oxabicyclo[4.2.0]octan-2-yl](hydroxy)methyl]-2,6,6-trimethylcyclohexa-2,4-dien-1-one |
| (XI)101438-18-a | 168421-67-8 | (5S)-5-[(S)-[(1S,2R,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-(2,2-dimethoxyethyl)-3-methyl-7-oxabicyclo[4.2.0]octan-2-yl](hydroxy)methyl]-5-hydroxy-2,6,6-trimethylcyclohex-2-en-1-one |
| (XII)101438-18-a | 168421-68-9 | (4S,5S)-4-[(1S,2R,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-(2,2-dimethoxyethyl)-3-methyl-7-oxabicyclo[4.2.0]octan-2-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-8-ene-2,7-dione |
| (XIII)101438-18-a | 168421-69-0 | (4S,5S)-4-[(1S,2R,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-(2,2-dimethoxyethyl)-3-methyl-7-oxabicyclo[4.2.0]octan-2-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]decane-2,7-dione |
| (XIV)101438-18-a | 168421-70-3 | (4S,5S)-4-[(1S,2R,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-(2,2-dimethoxyethyl)-3-methyl-7-oxabicyclo[4.2.0]octan-2-yl]-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-7-yl trifluoromethanesulfonate |
| (XV)101438-18-a | 168421-72-5 | (4S,5S)-4-[(1S,2R,3S,4S,6R)-1-(benzyloxy)-4-[(tert-butyldimethylsilyl)oxy]-3-methyl-3-(prop-2-en-1-yl)-7-oxabicyclo[4.2.0]octan-2-yl]-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-7-yl trifluoromethanesulfonate |
| (XVI)101438-18-a | 168421-73-6 | (1S,5S,6R,7S,10R,12S,13S)-7-(benzyloxy)-12-[(tert-butyldimethylsilyl)oxy]-13,17,20,20-tetramethyl-15-methylidene-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-3-one |
| (XVII)101438-18-a | 168421-75-8 | (1S,5S,6R,7S,10R,12S,13S)-7-(benzyloxy)-13,17,20,20-tetramethyl-15-methylidene-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-3-one |
| (XVIII)101438-18-a,(XVIII)101438-18-b | 168421-76-9 | (1S,4S,5S,7R,10S,11R,12S,16S,19R)-10-(benzyloxy)-4,19,21,21-tetramethyl-2-methylidene-5-[(triethylsilyl)oxy]-8,13,15,20-tetraoxahexacyclo[14.4.1.0(1,19).0(4,11).0(7,10).0(12,16)]henicosan-14-one |
OptimisedRoute 26Steps 7 · Total yield /
(XIX)101438-18-b168421-78-1(XVIII)101438-18-a,(XVIII)101438-18-b168421-76-9(XX)101438-18-b168421-79-2(XXI)101438-18-b168421-80-5(XXII)101438-18-b155588-13-9(XXIII)101438-18-b115437-21-3(XXIV)101438-18-b27548-93-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIX)101438-18-b | 168421-78-1 | (1S,4S,5S,7R,10S,11R,12S,16S,19R)-4,19,21,21-tetramethyl-2-methylidene-14-oxo-5-[(triethylsilyl)oxy]-8,13,15,20-tetraoxahexacyclo[14.4.1.0(1,19).0(4,11).0(7,10).0(12,16)]henicosan-10-yl acetate |
| (XVIII)101438-18-a,(XVIII)101438-18-b | 168421-76-9 | (1S,4S,5S,7R,10S,11R,12S,16S,19R)-10-(benzyloxy)-4,19,21,21-tetramethyl-2-methylidene-5-[(triethylsilyl)oxy]-8,13,15,20-tetraoxahexacyclo[14.4.1.0(1,19).0(4,11).0(7,10).0(12,16)]henicosan-14-one |
| (XX)101438-18-b | 168421-79-2 | (1S,4S,5S,7R,10S,11R,12S,13S,16R)-10-(acetyloxy)-13-hydroxy-4,16,18,18-tetramethyl-2-methylidene-5-[(triethylsilyl)oxy]-8,17-dioxapentacyclo[11.4.1.0(1,16).0(4,11).0(7,10)]octadecan-12-yl benzoate |
| (XXI)101438-18-b | 168421-80-5 | (1S,4S,5S,7R,10S,11R,12S,13S,16R)-10-(acetyloxy)-13-hydroxy-4,16,18,18-tetramethyl-2-oxo-5-[(triethylsilyl)oxy]-8,17-dioxapentacyclo[11.4.1.0(1,16).0(4,11).0(7,10)]octadecan-12-yl benzoate |
| (XXII)101438-18-b | 155588-13-9 | (1S,2S,3R,4S,7R,9S,10S,12R)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXIII)101438-18-b | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXIV)101438-18-b | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 27Steps 7 · Total yield /
(I)101438-19-a2935-35-5(II)101438-19-a37760-98-8(III)101438-19-a81912-50-7(IV)101438-19-a163010-72-8(IX)101438-19-a163010-81-9(V)101438-19-a79265-30-8(VI)101438-19-a163010-73-9(VII)101438-19-a77-76-9(VIII)101438-19-a163010-79-5(X)101438-19-a153652-70-1101438-19-a98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-19-a | 2935-35-5 | (S)-(+)-2-Phenylglycine |
| (II)101438-19-a | 37760-98-8 | L-Phenylglycine methyl ester |
| (III)101438-19-a | 81912-50-7 | methyl (2S)-2-phenyl-2-(phenylformamido)acetate |
| (IV)101438-19-a | 163010-72-8 | N-[(1S)-2-oxo-1-phenylethyl]benzamide |
| (IX)101438-19-a | 163010-81-9 | (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carbaldehyde |
| (V)101438-19-a | 79265-30-8 | 2-(trimethylsilyl)-1,3-thiazole |
| (VI)101438-19-a | 163010-73-9 | N-[(1S,2R)-2-hydroxy-1-phenyl-2-(1,3-thiazol-2-yl)ethyl]benzamide |
| (VII)101438-19-a | 77-76-9Available | 1-Methoxy-1-methylethyl methyl ether |
| (VIII)101438-19-a | 163010-79-5 | (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyl-5-(1,3-thiazol-2-yl)-1,3-oxazolidine |
| (X)101438-19-a | 153652-70-1 | (4S,5R)-3-benzoyl-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| 101438-19-a | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 28Steps 4 · Total yield /
(I)101438-20-a—(II)101438-20-a181375-35-9(III)101438-20-a—(IV)101438-20-a,(IV)101438-20-b133524-70-6(V)101438-20-a98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-20-a | - | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,12b-Diacetoxy-12-benzyloxy-9-[3(S)-hexanamido-2(R)-hydroxy-3-phenylpropionyloxy]-4,11-dihydroxy-4a,8,13,13-tetramethyl-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxet-5-one |
| (II)101438-20-a | 181375-35-9 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-hexanamido-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-20-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-[(E)-hexylideneamino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-20-a,(IV)101438-20-b | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (V)101438-20-a | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 29Steps 4 · Total yield /
(IX)101438-20-b157956-87-1(X)101438-20-b—(VII)101438-20-b181375-28-0(VIII)101438-20-b—(IV)101438-20-a,(IV)101438-20-b133524-70-6(VI)101438-20-b71610-00-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (IX)101438-20-b | 157956-87-1 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-{[(2R,3S)-3-(2-oxopropanamido)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy}-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (X)101438-20-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-{[(2R,3S)-3-[(E)-(2-oxopropylidene)amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy}-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VII)101438-20-b | 181375-28-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-15-{[(2R,3S)-3-[(2E)-2-methylbut-2-enamido]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy}-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VIII)101438-20-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1,9-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-[(E)-[(2E)-2-methylbut-2-en-1-ylidene]amino]-3-phenylpropanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-20-a,(IV)101438-20-b | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (VI)101438-20-b | 71610-00-9 | Benzoic acid (2alpha,5beta,7beta,10beta,13alpha)-4,10-diacetoxy-1,7-dihydroxy-13-[2(R)-hydroxy-3(S)-[2-methyl-2(E)-butenoylamino]-3-phenylpropionyloxy]-9-oxo-5,20-epoxytax-11-en-2-yl ester |
OptimisedRoute 30Steps 5 · Total yield /
(II)101438-21-a115437-21-3(III)101438-21-a186358-02-1(IV)101438-21-a,(IV)101438-21-b—(XI)101438-21-a32981-86-5(XII)101438-21-a115437-18-8(I)101438-21-a186357-99-3(X)101438-21-a186357-98-2(IX)101438-21-a159328-48-0(VIII)101438-21-a143615-00-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (II)101438-21-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-21-a | 186358-02-1 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-21-a,(IV)101438-21-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-amino-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XI)101438-21-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XII)101438-21-a | 115437-18-8 | (2alpha,5beta,7beta,10beta,13alpha)-4-Acetoxy-1,10,13-trihydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (I)101438-21-a | 186357-99-3 | (2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-[(benzyloxy)methoxy]-3-phenylpropanoic acid |
| (X)101438-21-a | 186357-98-2 | ethyl (2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-[(benzyloxy)methoxy]-3-phenylpropanoate |
| (IX)101438-21-a | 159328-48-0 | ethyl (2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoate |
| (VIII)101438-21-a | 143615-00-3 | Ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate |
OptimisedRoute 31Steps 3 · Total yield /
(VI)101438-21-b186358-03-2(VII)101438-21-b186358-04-3(IV)101438-21-a,(IV)101438-21-b—(V)101438-21-b98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (VI)101438-21-b | 186358-03-2 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-[(benzyloxy)methoxy]-3-phenyl-3-(phenylformamido)propanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VII)101438-21-b | 186358-04-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-[(benzyloxy)methoxy]-3-phenyl-3-(phenylformamido)propanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-21-a,(IV)101438-21-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-amino-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (V)101438-21-b | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 32Steps 8 · Total yield /
(I)101438-22-a79898-19-4(II)101438-22-a2916-68-9(III)101438-22-a188402-10-0(IV)101438-22-a—(IX)101438-22-a98-88-4(V)101438-22-a188402-12-2(VI)101438-22-a188402-19-9(VII)101438-22-a501-53-1(VIII)101438-22-a188402-20-2(X)101438-22-a188402-21-3(XI)101438-22-a115437-21-3(XII)101438-22-a188402-23-5API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-22-a | 79898-19-4 | (2R,3S)-3-phenyloxirane-2-carboxylic acid |
| (II)101438-22-a | 2916-68-9 | (2-Hydroxyethyl)trimethylsilane |
| (III)101438-22-a | 188402-10-0 | 2-(trimethylsilyl)ethyl (2R,3S)-3-phenyloxirane-2-carboxylate |
| (IV)101438-22-a | - | 2-(trimethylsilyl)ethyl (2S,3S)-3-bromo-2-hydroxy-3-phenylpropanoate |
| (IX)101438-22-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (V)101438-22-a | 188402-12-2 | 2-(trimethylsilyl)ethyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate |
| (VI)101438-22-a | 188402-19-9 | 2-(trimethylsilyl)ethyl (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoate |
| (VII)101438-22-a | 501-53-1Available | (Phenylmethyl)carbonochloridate |
| (VIII)101438-22-a | 188402-20-2 | 2-(trimethylsilyl)ethyl (2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-hydroxy-3-phenylpropanoate |
| (X)101438-22-a | 188402-21-3 | 2-(trimethylsilyl)ethyl (2R,3S)-2-(benzoyloxy)-3-{[(benzyloxy)carbonyl]amino}-3-phenylpropanoate |
| (XI)101438-22-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XII)101438-22-a | 188402-23-5 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-(benzoyloxy)-3-{[(benzyloxy)carbonyl]amino}-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 33Steps 5 · Total yield /
(I)101438-23-a99528-65-1(II)101438-23-a135791-11-6(III)101438-23-a247088-11-5(IV)101438-23-a—(V)101438-23-a99458-15-8101438-23-a132201-33-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-23-a | 99528-65-1 | methyl (2R,3R)-3-phenyloxirane-2-carboxylate |
| (II)101438-23-a | 135791-11-6 | methyl 3-azido-2-hydroxy-3-phenylpropanoate |
| (III)101438-23-a | 247088-11-5 | methyl 3-azido-2-oxo-3-phenylpropanoate |
| (IV)101438-23-a | - | methyl (2R)-3-azido-2-hydroxy-3-phenylpropanoate |
| (V)101438-23-a | 99458-15-8 | methyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate |
| 101438-23-a | 132201-33-3 | (2R,3S)-2-Hydroxy-3-phenyl-3-(phenylformamido)propanoic acid |
OptimisedRoute 34Steps 14 · Total yield /
(VIII)101438-24-a—(IX)101438-24-a—(VII)101438-24-a—(IV)101438-24-a219780-44-6(X)101438-24-a219780-51-5(XI)101438-24-a219780-52-6(XII)101438-24-a—(XVI)101438-24-a,(XVI)101438-24-b—(XIII)101438-24-a—(XV)101438-24-a—(XIV)101438-24-a—(V)101438-24-a—(I)101438-24-a219781-00-7(VI)101438-24-a—(III)101438-24-a219780-43-5(II)101438-24-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (VIII)101438-24-a | - | (1S,2S,3S,5S,9S,13S,18S)-2,3-dihydroxy-6,19,19-trimethyl-5-[(tributylsilyl)oxy]-10,12-dioxapentacyclo[7.7.2.1(3,7).0(1,18).0(13,18)]nonadec-6-ene-11,16-dione |
| (IX)101438-24-a | - | (1S,2S,4S,6S,8S,12S,13S,14S)-12,14-dihydroxy-9,19,19-trimethyl-4-phenyl-8-[(tributylsilyl)oxy]-3,5-dioxapentacyclo[11.4.1.1(6,10).0(1,13).0(2,6)]nonadec-9-en-17-one |
| (VII)101438-24-a | - | (1S,2S,6S,8S,12S,14S,16S,21S)-4,4-di-tert-butyl-9,22,22-trimethyl-14-phenyl-8-[(tributylsilyl)oxy]-3,5,13,15-tetraoxa-4-silahexacyclo[10.7.2.1(6,10).0(1,21).0(2,6).0(16,21)]docos-9-en-19-one |
| (IV)101438-24-a | 219780-44-6 | (1S,2S,9R,10R)-9-(benzyloxy)-1,2-dihydroxy-12,15,15-trimethyl-10-(phenylsulfanyl)tricyclo[9.3.1.0(3,8)]pentadeca-3,7,11-trien-13-one |
| (X)101438-24-a | 219780-51-5 | (1S,3S,5S,10S,11S,12S,16S)-11,15,18,18-tetramethyl-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,14-diene-7,10,12,16-tetrol |
| (XI)101438-24-a | 219780-52-6 | (1S,3S,5S,6R,10S,11S,12S,16S)-10,12,16-trihydroxy-11,15,18,18-tetramethyl-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-7-one |
| (XII)101438-24-a | - | (1S,3S,5S,6R,10S,11S,16S)-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-3-phenyl-16-[(tributylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-ene-7,12-dione |
| (XVI)101438-24-a,(XVI)101438-24-b | - | (1S,3S,5S,6R,7S,10R,12S,13S,15R,18S)-7-hydroxy-13,17,20,20-tetramethyl-14-oxo-3-phenyl-18-[(tributylsilyl)oxy]-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XIII)101438-24-a | - | (1S,3S,5S,6S,10S,11S,16S)-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-3-phenyl-16-[(tributylsilyl)oxy]-7-[(trimethylsilyl)methyl]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-12-one |
| (XV)101438-24-a | - | (1S,3S,5S,6S,8S,10S,11S,13R,16S)-8-chloro-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-7-methylidene-12-oxo-3-phenyl-16-[(tributylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
| (XIV)101438-24-a | - | (1S,3S,5S,6S,8S,10S,11S,16S)-8-chloro-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-7-methylidene-3-phenyl-16-[(tributylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-12-one |
| (V)101438-24-a | - | (1S,5S,12R,13R,16S)-12-(benzyloxy)-3,3-di-tert-butyl-15,18,18-trimethyl-13-(phenylsulfanyl)-16-[(tributylsilyl)oxy]-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,10,14-triene |
| (I)101438-24-a | 219781-00-7 | (1S,5Z)-1-hydroxy-4,6,6-trimethyl-5-[(phenylsulfanyl)methylidene]-3-{[tris(propan-2-yl)silyl]oxy}cyclohex-3-ene-1-carbaldehyde |
| (VI)101438-24-a | - | (2S,6S,8S,12S,16S,19R)-4,4-di-tert-butyl-9,21,21-trimethyl-14-phenyl-8-[(tributylsilyl)oxy]-3,5,13,15-tetraoxa-4-silapentacyclo[10.7.1.1(6,10).0(2,6).0(16,20)]henicosa-1(20),9-dien-19-ol |
| (III)101438-24-a | 219780-43-5 | {[(4S,5S,9E)-4-{6-[bis(benzyloxy)methyl]cyclohexa-1,5-dien-1-yl}-2,8,10,10-tetramethyl-9-[(phenylsulfanyl)methylidene]-1,3-dioxa-2-boraspiro[4.5]dec-7-en-7-yl]oxy}tris(propan-2-yl))silane |
| (II)101438-24-a | - | {6-[bis(benzyloxy)methyl]cyclohexa-1,5-dien-1-yl}lithium |
OptimisedRoute 35Steps 4 · Total yield /
(XVIII)101438-24-b—(XIX)101438-24-b—(XVI)101438-24-a,(XVI)101438-24-b—(XVII)101438-24-b—(XX)101438-24-b149249-91-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XVIII)101438-24-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-[(tributylsilyl)oxy]-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XIX)101438-24-b | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-[(tributylsilyl)oxy]-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XVI)101438-24-a,(XVI)101438-24-b | - | (1S,3S,5S,6R,7S,10R,12S,13S,15R,18S)-7-hydroxy-13,17,20,20-tetramethyl-14-oxo-3-phenyl-18-[(tributylsilyl)oxy]-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XVII)101438-24-b | - | (1S,5S,6R,7S,10R,12S,13S,15R,18S)-7-hydroxy-13,17,20,20-tetramethyl-3,14-dioxo-18-[(tributylsilyl)oxy]-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XX)101438-24-b | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
OptimisedRoute 36Steps 3 · Total yield /
(IV)101438-25-a241488-57-3(II)101438-25-a103150-33-0(I)101438-25-a27548-93-2(III)101438-25-a158722-22-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (IV)101438-25-a | 241488-57-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate |
| (II)101438-25-a | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (I)101438-25-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-25-a | 158722-22-6 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid |
OptimisedRoute 37Steps 3 · Total yield /
(I)101438-26-a27548-93-2(III)101438-26-a158722-22-6(V)101438-26-a182158-93-6(VI)101438-26-a241488-58-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-26-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-26-a | 158722-22-6 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid |
| (V)101438-26-a | 182158-93-6 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[(benzyloxy)carbonyl]oxy}-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VI)101438-26-a | 241488-58-4 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-9-{[(benzyloxy)carbonyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate |
OptimisedRoute 38Steps 3 · Total yield /
(I)101438-27-a27548-93-2(III)101438-27-a158722-22-6(VII)101438-27-a225219-09-0(VIII)101438-27-a241488-59-5API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-27-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-27-a | 158722-22-6 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid |
| (VII)101438-27-a | 225219-09-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[(tert-butoxy)carbonyl]oxy}-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VIII)101438-27-a | 241488-59-5 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-9-{[(tert-butoxy)carbonyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate |
OptimisedRoute 39Steps 3 · Total yield /
(I)101438-28-a27548-93-2(II)101438-28-a103150-33-0(IX)101438-28-a149107-92-6(X)101438-28-a114915-17-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-28-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-28-a | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (IX)101438-28-a | 149107-92-6 | (3R,4S)-1-benzoyl-3-[(2-methoxypropan-2-yl)oxy]-4-phenylazetidin-2-one |
| (X)101438-28-a | 114915-17-2 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 40Steps 3 · Total yield /
(I)101438-29-a27548-93-2(IX)101438-29-a225219-09-0(V)101438-29-a182158-93-6(XI)101438-29-a160237-53-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-29-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (IX)101438-29-a | 225219-09-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[(tert-butoxy)carbonyl]oxy}-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (V)101438-29-a | 182158-93-6 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[(benzyloxy)carbonyl]oxy}-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XI)101438-29-a | 160237-53-6 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[(benzyloxy)carbonyl]oxy}-1-hydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 41Steps 2 · Total yield /
(I)101438-30-a27548-93-2(IX)101438-30-a149107-92-6(VII)101438-30-a225219-09-0API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-30-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (IX)101438-30-a | 149107-92-6 | (3R,4S)-1-benzoyl-3-[(2-methoxypropan-2-yl)oxy]-4-phenylazetidin-2-one |
| (VII)101438-30-a | 225219-09-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[(tert-butoxy)carbonyl]oxy}-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 42Steps 14 · Total yield /
(I)101438-31-a80-57-9(II)101438-31-a870-63-3(III)101438-31-a1824589-22-1(IV)101438-31-a1824564-48-8(IX)101438-31-a—(V)101438-31-a623-47-2(VI)101438-31-a—(VII)101438-31-a—(VIII)101438-31-a—(X)101438-31-a—(XI)101438-31-a—(XII)101438-31-a—(XIII)101438-31-a—(XIV)101438-31-a187961-42-8(XV)101438-31-a187960-83-4(XVI)101438-31-a187960-85-6(XVII)101438-31-a,(XVII)101438-31-b187960-87-8API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-31-a | 80-57-9 | 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-one |
| (II)101438-31-a | 870-63-3 | 1-Bromo-3-methyl-2-butene |
| (III)101438-31-a | 1824589-22-1 | 2-{2,6,6-trimethyl-4-oxobicyclo[3.1.1]hept-2-en-3-yl}acetaldehyde |
| (IV)101438-31-a | 1824564-48-8 | 2-{2,6,6-trimethyl-7-oxobicyclo[3.1.1]hept-2-en-1-yl}acetaldehyde |
| (IX)101438-31-a | - | ethyl (2S,6R)-2,6-dihydroxy-4,10,11,11-tetramethyl-3-oxotricyclo[5.3.1.0(1,6)]undeca-4,9-diene-5-carboxylate |
| (V)101438-31-a | 623-47-2Available | (Ethoxycarbonyl)acetylene |
| (VI)101438-31-a | - | ethyl 5-{2,6,6-trimethyl-7-oxobicyclo[3.1.1]hept-2-en-1-yl}-4-[(trimethylsilyl)oxy]pent-2-ynoate |
| (VII)101438-31-a | - | ethyl (6R)-3,6-dihydroxy-4,10,11,11-tetramethyltricyclo[5.3.1.0(1,6)]undeca-4,9-diene-5-carboxylate |
| (VIII)101438-31-a | - | ethyl (6R)-6-hydroxy-4,10,11,11-tetramethyl-3-oxotricyclo[5.3.1.0(1,6)]undeca-4,9-diene-5-carboxylate |
| (X)101438-31-a | - | (2S,3S,6S)-5-(hydroxymethyl)-4,10,11,11-tetramethyltricyclo[5.3.1.0(1,6)]undeca-4,9-diene-2,3,6-triol |
| (XI)101438-31-a | - | (2S,6S,9S)-8-{[(tert-butyldimethylsilyl)oxy]methyl}-4,4,7,13,14,14-hexamethyl-3,5-dioxatetracyclo[8.3.1.0(1,9).0(2,6)]tetradeca-7,12-dien-9-ol |
| (XII)101438-31-a | - | (2S,6S,7Z,12S)-8-{[(tert-butyldimethylsilyl)oxy]methyl}-4,4,7,13,14,14-hexamethyl-12-{[tris(propan-2-yl)silyl]oxy}-3,5-dioxatricyclo[8.3.1.0(2,6)]tetradeca-1(13),7-dien-9-one |
| (XIII)101438-31-a | - | (2S,6S,7Z,9S,10S,12S)-8-(hydroxymethyl)-4,4,7,13,14,14-hexamethyl-12-[(triisopropylsilyl)oxy]-3,5-dioxatricyclo[8.3.1.0(2,6)]tetradeca-1(13),7-diene-9,10-diol |
| (XIV)101438-31-a | 187961-42-8 | (1S,5S,6S,7S,8S,12S,15S)-7,10,10,14,17,17-hexamethyl-6-{[(trimethylsilyl)oxy]methyl}-15-{[tris(propan-2-yl)silyl]oxy}-2,4,9,11-tetraoxatetracyclo[11.3.1.0(1,5).0(8,12)]heptadec-13-en-3-one |
| (XV)101438-31-a | 187960-83-4 | (1S,5S,6R,7S,8S,12S,15S)-7,10,10,14,17,17-hexamethyl-3-oxo-15-[(triisopropylsilyl)oxy]-2,4,9,11-tetraoxatetracyclo[11.3.1.0(1,5).0(8,12)]heptadec-13-ene-6-carbaldehyde |
| (XVI)101438-31-a | 187960-85-6 | 2-[(1S,5S,6R,7S,8S,9S,12S)-8,9-dihydroxy-7,11,14,14-tetramethyl-3-oxo-12-{[tris(propan-2-yl)silyl]oxy}-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-en-6-yl]acetaldehyde |
| (XVII)101438-31-a,(XVII)101438-31-b | 187960-87-8 | 2-[(1S,5S,6S,7S,8S,12S)-7,11,14,14-tetramethyl-3,9-dioxo-8-[(triethylsilyl)oxy]-12-[(triisopropylsilyl)oxy]-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-en-6-yl]prop-2-enal |
OptimisedRoute 43Steps 11 · Total yield /
(XIX)101438-31-b187960-90-3(XVII)101438-31-a,(XVII)101438-31-b187960-87-8(XVIII)101438-31-b187960-89-0(XX)101438-31-b5807-14-7(XXI)101438-31-b187960-91-4(XXII)101438-31-b187960-92-5(XXIII)101438-31-b187960-93-6(XXIV)101438-31-b187960-94-7(XXIX)101438-31-b,(XXIX)101438-31-c187961-01-9(XXV)101438-31-b187960-95-8(XXVI)101438-31-b187960-96-9(XXVII)101438-31-b187960-97-0(XXVIII)101438-31-b187960-99-2101438-31-b1730-25-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIX)101438-31-b | 187960-90-3 | (1S,2S,3S,4S,5S,9S)-5-(acetyloxy)-3-[(3R)-3-[(benzyloxy)methoxy]hexa-1,5-dien-2-yl]-1-hydroxy-4,8,11,11-tetramethyl-6-oxo-9-[(triisopropylsilyl)oxy]bicyclo[5.3.1]undec-7-en-2-yl benzoate |
| (XVII)101438-31-a,(XVII)101438-31-b | 187960-87-8 | 2-[(1S,5S,6S,7S,8S,12S)-7,11,14,14-tetramethyl-3,9-dioxo-8-[(triethylsilyl)oxy]-12-[(triisopropylsilyl)oxy]-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-en-6-yl]prop-2-enal |
| (XVIII)101438-31-b | 187960-89-0 | (1S,5S,6S,7S,8S,12S)-6-[(3R)-3-[(benzyloxy)methoxy]hexa-1,5-dien-2-yl]-7,11,14,14-tetramethyl-8-[(triethylsilyl)oxy]-12-{[tris(propan-2-yl)silyl]oxy}-2,4-dioxatricyclo[8.3.1.0(1,5)]tetradec-10-ene-3,9-dione |
| (XX)101438-31-b | 5807-14-7 | 1,3,4,6,7,8-Hexahydro-2H-pyrimido[1,2-a]pyrimidine |
| (XXI)101438-31-b | 187960-91-4 | (1S,2S,3S,4S,6R,9S)-6-(acetyloxy)-3-[(3R)-3-[(benzyloxy)methoxy]hexa-1,5-dien-2-yl]-1-hydroxy-4,8,11,11-tetramethyl-5-oxo-9-{[tris(propan-2-yl)silyl]oxy}bicyclo[5.3.1]undec-7-en-2-yl benzoate |
| (XXII)101438-31-b | 187960-92-5 | (1S,2S,3S,4S,6R,9S)-6-(acetyloxy)-3-[(3R)-3-[(benzyloxy)methoxy]-5-oxopent-1-en-2-yl]-1-hydroxy-4,8,11,11-tetramethyl-5-oxo-9-{[tris(propan-2-yl)silyl]oxy}bicyclo[5.3.1]undec-7-en-2-yl benzoate |
| (XXIII)101438-31-b | 187960-93-6 | (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetyloxy)-5-[(benzyloxy)methoxy]-1,7-dihydroxy-8,12,15,15-tetramethyl-4-methylidene-9-oxo-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXIV)101438-31-b | 187960-94-7 | (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetyloxy)-5-[(benzyloxy)methoxy]-1-hydroxy-8,12,15,15-tetramethyl-4-methylidene-9-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-13-{[tris(propan-2-yl)silyl]oxy}tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXIX)101438-31-b,(XXIX)101438-31-c | 187961-01-9 | (1S,5S,6R,7S,10R,12S,13S,15R,18S)-15-(acetyloxy)-13,17,20,20-tetramethyl-3,14-dioxo-12-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-18-[(triisopropylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
| (XXV)101438-31-b | 187960-95-8 | (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetyloxy)-1,5-dihydroxy-8,12,15,15-tetramethyl-4-methylidene-9-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXVI)101438-31-b | 187960-96-9 | (1S,2S,3R,5R,7S,8S,10R,13S)-10-(acetyloxy)-1-hydroxy-5-(methanesulfonyloxy)-8,12,15,15-tetramethyl-4-methylidene-9-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-13-{[tris(propan-2-yl)silyl]oxy}tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXVII)101438-31-b | 187960-97-0 | (1S,2S,3S,5S,7S,8S,10R,13S)-10-(acetyloxy)-5-bromo-1-hydroxy-8,12,15,15-tetramethyl-4-methylidene-9-oxo-7-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-13-[(triisopropylsilyl)oxy]tricyclo[9.3.1.0(3,8)]pentadec-11-en-2-yl benzoate |
| (XXVIII)101438-31-b | 187960-99-2 | (1S,5S,6R,7S,8S,10S,11S,13R,16S)-8-bromo-7-hydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3,12-dioxo-10-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-16-{[tris(propan-2-yl)silyl]oxy}-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
| 101438-31-b | 1730-25-2 | Allyl(bromo)magnesium |
OptimisedRoute 44Steps 1 · Total yield /
(XXX)101438-31-c27548-93-2(XXIX)101438-31-b,(XXIX)101438-31-c187961-01-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXX)101438-31-c | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XXIX)101438-31-b,(XXIX)101438-31-c | 187961-01-9 | (1S,5S,6R,7S,10R,12S,13S,15R,18S)-15-(acetyloxy)-13,17,20,20-tetramethyl-3,14-dioxo-12-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-18-[(triisopropylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
OptimisedRoute 45Steps 5 · Total yield /
(I)101438-32-a103-26-4(II)101438-32-a122743-18-4(III)101438-32-a707-07-3(IV)101438-32-a—(V)101438-32-a—(VI)101438-32-a—(VII)101438-32-a32981-85-4(VIII)101438-32-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-32-a | 103-26-4 | 3-Phenyl-2-propenoic acid methyl ester |
| (II)101438-32-a | 122743-18-4 | Methyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate |
| (III)101438-32-a | 707-07-3Available | (Trimethoxymethyl)benzene |
| (IV)101438-32-a | - | (1S,2R)-1-Hydroxy-3-methoxy-3-oxo-1-phenylpropan-2-yl benzoate |
| (V)101438-32-a | - | (1R,2S)-1-Bromo-3-methoxy-3-oxo-1-phenylpropan-2-yl benzoate |
| (VI)101438-32-a | - | (1S,2R)-1-Azido-3-methoxy-3-oxo-1-phenylpropan-2-yl benzoate |
| (VII)101438-32-a | 32981-85-4 | Methyl (2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoate |
| (VIII)101438-32-a | - | Methyl 3-benzamido-2-oxo-3-phenylpropanoate |
OptimisedRoute 46Steps 4 · Total yield /
(I)101438-33-a32981-86-5(II)101438-33-a1719-53-5(III)101438-33-a310445-90-0(IV)101438-33-a310446-30-1(V)101438-33-a158722-22-6(VI)101438-33-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-33-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-33-a | 1719-53-5 | dichlorodiethylsilane |
| (III)101438-33-a | 310445-90-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetyloxy)-9-{[diethyl(methoxy)silyl]oxy}-1,12,15-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-33-a | 310446-30-1 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-9-{[diethyl(methoxy)silyl]oxy}-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (V)101438-33-a | 158722-22-6 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid |
| (VI)101438-33-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-9-{[diethyl(methoxy)silyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate |
OptimisedRoute 47Steps 10 · Total yield /
(I)101438-34-a87-91-2(II)101438-34-a84379-51-1(III)101438-34-a129492-58-6(IV)101438-34-a100-46-9(IX)101438-34-a—(V)101438-34-a—(VI)101438-34-a165104-99-4(VII)101438-34-a165104-98-3(VIII)101438-34-a—(X)101438-34-a131968-74-6(XI)101438-34-a350583-44-7(XII)101438-34-a149140-54-5(XIII)101438-34-a149249-91-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-34-a | 87-91-2 | (+)-Diethyl L-tartrate |
| (II)101438-34-a | 84379-51-1 | (2S,3S)-3-(benzyloxy)butane-1,2,4-triol |
| (III)101438-34-a | 129492-58-6 | (2S)-2-(benzyloxy)-3-hydroxypropanal |
| (IV)101438-34-a | 100-46-9Available | 1-Phenylmethylamine |
| (IX)101438-34-a | - | methyl (2R,3S)-3-(benzylamino)-2-(benzyloxy)-3-phenylpropanoate |
| (V)101438-34-a | - | (2R,3Z)-3-(benzylimino)-2-(benzyloxy)propan-1-ol |
| (VI)101438-34-a | 165104-99-4 | (2R,3R)-3-(benzylamino)-2-(benzyloxy)-3-phenylpropan-1-ol |
| (VII)101438-34-a | 165104-98-3 | (2R,3S)-3-(benzylamino)-2-(benzyloxy)-3-phenylpropan-1-ol |
| (VIII)101438-34-a | - | (2R,3S)-3-(benzylamino)-2-(benzyloxy)-3-phenylpropanoic acid |
| (X)101438-34-a | 131968-74-6 | (2R,3S)-3-Phenylisoserine methyl ester |
| (XI)101438-34-a | 350583-44-7 | methyl (2R,3S)-3-amino-3-phenyl-2-[(triethylsilyl)oxy]propanoate |
| (XII)101438-34-a | 149140-54-5 | (3R,4S)-4-Phenyl-3-[(triethylsilyl)oxy]azetidin-2-one |
| (XIII)101438-34-a | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
OptimisedRoute 48Steps 17 · Total yield /
(I)101438-35-a6089-04-9(II)101438-35-a123-38-6(III)101438-35-a14092-31-0(IV)101438-35-a—(IX)101438-35-a219780-60-6(V)101438-35-a—(VI)101438-35-a—(VII)101438-35-a157635-52-4(VIII)101438-35-a—(X)101438-35-a160147-03-5(XI)101438-35-a162084-40-4(XII)101438-35-a162084-44-8(XIII)101438-35-a162084-45-9(XIV)101438-35-a,(XIV)101438-35-e219781-00-7(XIX)101438-35-a219780-70-8(XV)101438-35-a219780-42-4(XVI)101438-35-a272439-89-1(XVII)101438-35-a219780-43-5(XVIII)101438-35-a219780-69-5(XX)101438-35-a219780-45-7(XXI)101438-35-a,(XXI)101438-35-b219780-74-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-35-a | 6089-04-9 | 2-(2-Propynyloxy)tetrahydropyran |
| (II)101438-35-a | 123-38-6Available | Methyl acetaldehyde |
| (III)101438-35-a | 14092-31-0 | 6-(oxan-2-yloxy)hex-4-yn-3-ol |
| (IV)101438-35-a | - | (4Z)-6-(oxan-2-yloxy)hex-4-en-3-ol |
| (IX)101438-35-a | 219780-60-6 | 5-(hydroxymethyl)-2,4,4-trimethyl-3-oxocyclohex-1-en-1-yl 2,2-dimethylpropanoate |
| (V)101438-35-a | - | (4Z)-6-(oxan-2-yloxy)hex-4-en-3-one |
| (VI)101438-35-a | - | lithium(1+) ion 1-ethoxy-2-methylprop-1-en-1-olate |
| (VII)101438-35-a | 157635-52-4 | ethyl 2,2-dimethyl-3-[(oxan-2-yloxy)methyl]-5-oxoheptanoate |
| (VIII)101438-35-a | - | 2,4,4-trimethyl-5-[(oxan-2-yloxy)methyl]-3-oxocyclohex-1-en-1-yl 2,2-dimethylpropanoate |
| (X)101438-35-a | 160147-03-5 | 5-formyl-2,4,4-trimethyl-3-oxocyclohex-1-en-1-yl 2,2-dimethylpropanoate |
| (XI)101438-35-a | 162084-40-4 | (5E)-2,4,4-trimethyl-3-oxo-5-{[(triisopropylsilyl)oxy]methylidene}cyclohex-1-en-1-yl 2,2-dimethylpropanoate |
| (XII)101438-35-a | 162084-44-8 | (5S)-5-formyl-5-hydroxy-2,4,4-trimethyl-3-oxocyclohex-1-en-1-yl 2,2-dimethylpropanoate |
| (XIII)101438-35-a | 162084-45-9 | (1S)-1-hydroxy-4,6,6-trimethyl-5-oxo-3-[(triisopropylsilyl)oxy]cyclohex-3-ene-1-carbaldehyde |
| (XIV)101438-35-a,(XIV)101438-35-e | 219781-00-7 | (1S,5Z)-1-hydroxy-4,6,6-trimethyl-5-[(phenylsulfanyl)methylidene]-3-{[tris(propan-2-yl)silyl]oxy}cyclohex-3-ene-1-carbaldehyde |
| (XIX)101438-35-a | 219780-70-8 | (1S,5S,12R,13R)-12-(benzyloxy)-3,3-di-tert-butyl-15,18,18-trimethyl-13-(phenylsulfanyl)-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,10,14-trien-16-one |
| (XV)101438-35-a | 219780-42-4 | {[(benzyloxy)(6-bromocyclohexa-1,5-dien-1-yl)methoxy]methyl}benzene |
| (XVI)101438-35-a | 272439-89-1 | (1S,5E)-1-[(S)-{6-[bis(benzyloxy)methyl]cyclohexa-1,5-dien-1-yl}(hydroxy)methyl]-4,6,6-trimethyl-5-[(phenylsulfanyl)methylidene]-3-[(triisopropylsilyl)oxy]cyclohex-3-en-1-ol |
| (XVII)101438-35-a | 219780-43-5 | {[(4S,5S,9E)-4-{6-[bis(benzyloxy)methyl]cyclohexa-1,5-dien-1-yl}-2,8,10,10-tetramethyl-9-[(phenylsulfanyl)methylidene]-1,3-dioxa-2-boraspiro[4.5]dec-7-en-7-yl]oxy}tris(propan-2-yl))silane |
| (XVIII)101438-35-a | 219780-69-5 | (1S,5S,12R,13R)-12-(benzyloxy)-3,15,18,18-tetramethyl-13-(phenylsulfanyl)-2,4-dioxa-3-boratetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,10,14-trien-16-one |
| (XX)101438-35-a | 219780-45-7 | (1S,5S,12R,13R,16S)-12-(benzyloxy)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-13-(phenylsulfanyl)-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,10,14-triene |
| (XXI)101438-35-a,(XXI)101438-35-b | 219780-74-2 | (1S,5S,7R,10S,12S,16S)-12-(benzyloxy)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6(11),14-diene-7,10-diol |
OptimisedRoute 49Steps 13 · Total yield /
(XXI)101438-35-a,(XXI)101438-35-b219780-74-2(XXII)101438-35-b,(XXII)101438-35-e219780-75-3(XXIII)101438-35-b219780-47-9(XXIV)101438-35-b219780-76-4(XXIX)101438-35-b219780-52-6(XXV)101438-35-b219780-48-0(XXVI)101438-35-b219780-79-7(XXVII)101438-35-b219780-49-1(XXVIII)101438-35-b219780-81-1(XXX)101438-35-b219780-82-2(XXXI)101438-35-b219780-83-3(XXXII)101438-35-b219780-84-4(XXXIII)101438-35-b,(XXXIII)101438-35-c116-11-0(XXXIV)101438-35-b219780-53-7(XXXV)101438-35-b,(XXXV)101438-35-c219780-87-7API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXI)101438-35-a,(XXI)101438-35-b | 219780-74-2 | (1S,5S,7R,10S,12S,16S)-12-(benzyloxy)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6(11),14-diene-7,10-diol |
| (XXII)101438-35-b,(XXII)101438-35-e | 219780-75-3 | (1S,5S,7R,10S,12S,16S)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6(11),14-diene-7,10,12-triol |
| (XXIII)101438-35-b | 219780-47-9 | (2S,6S,8S,12S,16S,19R)-4,4-di-tert-butyl-8-[(tert-butyldimethylsilyl)oxy]-9,21,21-trimethyl-14-phenyl-3,5,13,15-tetraoxa-4-silapentacyclo[10.7.1.1(6,10).0(2,6).0(16,20)]henicosa-1(20),9-dien-19-ol |
| (XXIV)101438-35-b | 219780-76-4 | (1R,2S,6S,8S,12S,14S,16S,19R,21S)-4,4-di-tert-butyl-8-[(tert-butyldimethylsilyl)oxy]-9,22,22-trimethyl-14-phenyl-3,5,13,15-tetraoxa-4-silahexacyclo[10.7.2.1(6,10).0(1,21).0(2,6).0(16,21)]docos-9-en-19-ol |
| (XXIX)101438-35-b | 219780-52-6 | (1S,3S,5S,6R,10S,11S,12S,16S)-10,12,16-trihydroxy-11,15,18,18-tetramethyl-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-7-one |
| (XXV)101438-35-b | 219780-48-0 | (1S,2S,6S,8S,12S,14S,16S,21S)-4,4-di-tert-butyl-8-[(tert-butyldimethylsilyl)oxy]-9,22,22-trimethyl-14-phenyl-3,5,13,15-tetraoxa-4-silahexacyclo[10.7.2.1(6,10).0(1,21).0(2,6).0(16,21)]docos-9-en-19-one |
| (XXVI)101438-35-b | 219780-79-7 | (1S,2S,3S,5S,9S,13S,18S)-5-[(tert-butyldimethylsilyl)oxy]-2,3-dihydroxy-6,19,19-trimethyl-10,12-dioxapentacyclo[7.7.2.1(3,7).0(1,18).0(13,18)]nonadec-6-ene-11,16-dione |
| (XXVII)101438-35-b | 219780-49-1 | (1S,2S,4S,6S,8S,12S,13S,14S)-8-[(tert-butyldimethylsilyl)oxy]-12,14-dihydroxy-9,19,19-trimethyl-4-phenyl-3,5-dioxapentacyclo[11.4.1.1(6,10).0(1,13).0(2,6)]nonadec-9-en-17-one |
| (XXVIII)101438-35-b | 219780-81-1 | (1S,3S,5S,10S,11S,12S,16S)-16-[(tert-butyldimethylsilyl)oxy]-11,15,18,18-tetramethyl-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,14-diene-7,10,12-triol |
| (XXX)101438-35-b | 219780-82-2 | (1R,2S,4S,6S,8S,12S,16S,20S)-8-hydroxy-9,20,21,21-tetramethyl-4,14-diphenyl-3,5,13,15-tetraoxa-14-borapentacyclo[10.7.1.1(6,10).0(2,6).0(16,20)]henicos-9-en-19-one |
| (XXXI)101438-35-b | 219780-83-3 | (1R,2S,4S,6S,8S,12S,16S,20S)-8-[(tert-butyldimethylsilyl)oxy]-9,20,21,21-tetramethyl-4,14-diphenyl-3,5,13,15-tetraoxa-14-borapentacyclo[10.7.1.1(6,10).0(2,6).0(16,20)]henicos-9-en-19-one |
| (XXXII)101438-35-b | 219780-84-4 | (1S,3S,5S,6R,10S,11S,12S,16S)-16-[(tert-butyldimethylsilyl)oxy]-10,12-dihydroxy-11,15,18,18-tetramethyl-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-7-one |
| (XXXIII)101438-35-b,(XXXIII)101438-35-c | 116-11-0 | 2-Methoxy-1-propene |
| (XXXIV)101438-35-b | 219780-53-7 | (1S,3S,5S,6R,10S,11S,16S)-16-[(tert-butyldimethylsilyl)oxy]-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-ene-7,12-dione |
| (XXXV)101438-35-b,(XXXV)101438-35-c | 219780-87-7 | (1S,3S,5S,6R,10S,11S,16S)-16-[(tert-butyldimethylsilyl)oxy]-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-7-yl trifluoromethanesulfonate |
OptimisedRoute 50Steps 12 · Total yield /
(XL)101438-35-c219780-91-3(XLI)101438-35-c219780-92-4(XLII)101438-35-c219780-58-2(XLIII)101438-35-c219780-95-7(XLIV)101438-35-c219780-96-8(XLV)101438-35-c189441-63-2(XLVI)101438-35-c219780-59-3(XLVII)101438-35-c,(XLVII)101438-35-d103150-33-0(XXXIII)101438-35-b,(XXXIII)101438-35-c116-11-0(XXXIX)101438-35-c219780-56-0(XXXV)101438-35-b,(XXXV)101438-35-c219780-87-7(XXXVI)101438-35-c219780-54-8(XXXVII)101438-35-c219780-55-9(XXXVIII)101438-35-c219780-90-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XL)101438-35-c | 219780-91-3 | (1S,3S,5S,6R,7S,8S,10S,11S,13R,16S)-16-[(tert-butyldimethylsilyl)oxy]-8-chloro-7-hydroxy-7-(hydroxymethyl)-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
| (XLI)101438-35-c | 219780-92-4 | (1S,3S,5S,6R,7S,10R,12S,13S,15R,18S)-18-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-12-[(2-methoxypropan-2-yl)oxy]-13,17,20,20-tetramethyl-14-oxo-3-phenyl-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XLII)101438-35-c | 219780-58-2 | (1S,3S,5S,6R,7S,10R,12S,13S,15R,18S)-18-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-13,17,20,20-tetramethyl-14-oxo-3-phenyl-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XLIII)101438-35-c | 219780-95-7 | (1S,5S,6R,7S,10R,12S,13S,15R,18S)-18-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-13,17,20,20-tetramethyl-3,14-dioxo-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-15-yl acetate |
| (XLIV)101438-35-c | 219780-96-8 | (1S,5S,6R,7S,10R,12S,13S,15R,18S)-15-(acetyloxy)-18-[(tert-butyldimethylsilyl)oxy]-13,17,20,20-tetramethyl-3,14-dioxo-12-[(triethylsilyl)oxy]-2,4,9-trioxapentacyclo[14.3.1.0(1,5).0(6,13).0(7,10)]icos-16-en-7-yl acetate |
| (XLV)101438-35-c | 189441-63-2 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XLVI)101438-35-c | 219780-59-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XLVII)101438-35-c,(XLVII)101438-35-d | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XXXIII)101438-35-b,(XXXIII)101438-35-c | 116-11-0 | 2-Methoxy-1-propene |
| (XXXIX)101438-35-c | 219780-56-0 | (1S,3S,5S,6S,8S,10S,11S,13R,16S)-16-[(tert-butyldimethylsilyl)oxy]-8-chloro-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-7-methylidene-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
| (XXXV)101438-35-b,(XXXV)101438-35-c | 219780-87-7 | (1S,3S,5S,6R,10S,11S,16S)-16-[(tert-butyldimethylsilyl)oxy]-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-7-yl trifluoromethanesulfonate |
| (XXXVI)101438-35-c | 219780-54-8 | (1S,3S,5S,6S,10S,11S,16S)-16-[(tert-butyldimethylsilyl)oxy]-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-3-phenyl-7-[(trimethylsilyl)methyl]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-7,14-dien-12-one |
| (XXXVII)101438-35-c | 219780-55-9 | (1S,3S,5S,6S,8S,10S,11S,16S)-16-[(tert-butyldimethylsilyl)oxy]-8-chloro-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-7-methylidene-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-12-one |
| (XXXVIII)101438-35-c | 219780-90-2 | (1S,3S,5S,6S,8S,10S,11S,13S,16S)-16-[(tert-butyldimethylsilyl)oxy]-8-chloro-10-[(2-methoxypropan-2-yl)oxy]-11,15,18,18-tetramethyl-7-methylidene-12-oxo-3-phenyl-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-13-yl acetate |
OptimisedRoute 51Steps 2 · Total yield /
(XLIX)101438-35-d219780-99-1(XLVII)101438-35-c,(XLVII)101438-35-d103150-33-0(XLVIII)101438-35-d149249-91-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XLIX)101438-35-d | 219780-99-1 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XLVII)101438-35-c,(XLVII)101438-35-d | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XLVIII)101438-35-d | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
OptimisedRoute 52Steps 12 · Total yield /
(L)101438-35-e272439-92-6(LI)101438-35-e1053633-20-7(LII)101438-35-e272440-07-0(LIII)101438-35-e—(LIV)101438-35-e272439-93-7(LIX)101438-35-e272439-98-2(LV)101438-35-e272439-94-8(LVI)101438-35-e272440-08-1(LVII)101438-35-e272439-95-9(LVIII)101438-35-e272439-96-0(LX)101438-35-e272440-11-6(LXI)101438-35-e272440-12-7(XIV)101438-35-a,(XIV)101438-35-e219781-00-7(XXII)101438-35-b,(XXII)101438-35-e219780-75-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (L)101438-35-e | 272439-92-6 | 1-[bis(benzyloxy)methyl]-2-bromobenzene |
| (LI)101438-35-e | 1053633-20-7 | (1S,5E)-1-[(S)-{2-[bis(benzyloxy)methyl]phenyl}(hydroxy)methyl]-4,6,6-trimethyl-5-[(phenylsulfanyl)methylidene]-3-{[tris(propan-2-yl)silyl]oxy}cyclohex-3-en-1-ol |
| (LII)101438-35-e | 272440-07-0 | {[(4S,5S,9E)-4-{2-[bis(benzyloxy)methyl]phenyl}-2,8,10,10-tetramethyl-9-[(phenylsulfanyl)methylidene]-1,3-dioxa-2-boraspiro[4.5]dec-7-en-7-yl]oxy}triisopropylsilane |
| (LIII)101438-35-e | - | (1S,5S,12R,13R)-12-(benzyloxy)-3,15,18,18-tetramethyl-13-(phenylsulfanyl)-2,4-dioxa-3-boratetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,8,10,14-tetraen-16-one |
| (LIV)101438-35-e | 272439-93-7 | (1S,2S,9R,10R)-9-(benzyloxy)-1,2-dihydroxy-12,15,15-trimethyl-10-(phenylsulfanyl)tricyclo[9.3.1.0(3,8)]pentadeca-3,5,7,11-tetraen-13-one |
| (LIX)101438-35-e | 272439-98-2 | (1S,2S,13S)-13-[(tert-butyldimethylsilyl)oxy]-1,2-dihydroxy-12,15,15-trimethyltricyclo[9.3.1.0(3,8)]pentadeca-3,7,11-trien-9-one |
| (LV)101438-35-e | 272439-94-8 | (1S,2S,9R,10R,13S)-9-(benzyloxy)-2,13-bis[(tert-butyldimethylsilyl)oxy]-12,15,15-trimethyl-10-(phenylsulfanyl)tricyclo[9.3.1.0(3,8)]pentadeca-3,5,7,11-tetraen-1-ol |
| (LVI)101438-35-e | 272440-08-1 | (1S,2S,9S,13S)-9-(benzyloxy)-2,13-bis[(tert-butyldimethylsilyl)oxy]-12,15,15-trimethyltricyclo[9.3.1.0(3,8)]pentadeca-3,5,7,11-tetraen-1-ol |
| (LVII)101438-35-e | 272439-95-9 | (1S,2S,13S)-2,13-bis[(tert-butyldimethylsilyl)oxy]-1-hydroxy-12,15,15-trimethyltricyclo[9.3.1.0(3,8)]pentadeca-3,5,7,11-tetraen-9-one |
| (LVIII)101438-35-e | 272439-96-0 | (1S,2S,13S)-2,13-bis[(tert-butyldimethylsilyl)oxy]-1-hydroxy-12,15,15-trimethyltricyclo[9.3.1.0(3,8)]pentadeca-3,7,11-trien-9-one |
| (LX)101438-35-e | 272440-11-6 | (1S,5S,16S)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,10,14-trien-12-one |
| (LXI)101438-35-e | 272440-12-7 | (1S,5S,12S,16S)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6,10,14-trien-12-ol |
| (XIV)101438-35-a,(XIV)101438-35-e | 219781-00-7 | (1S,5Z)-1-hydroxy-4,6,6-trimethyl-5-[(phenylsulfanyl)methylidene]-3-{[tris(propan-2-yl)silyl]oxy}cyclohex-3-ene-1-carbaldehyde |
| (XXII)101438-35-b,(XXII)101438-35-e | 219780-75-3 | (1S,5S,7R,10S,12S,16S)-3,3-di-tert-butyl-16-[(tert-butyldimethylsilyl)oxy]-15,18,18-trimethyl-2,4-dioxa-3-silatetracyclo[12.3.1.0(1,5).0(6,11)]octadeca-6(11),14-diene-7,10,12-triol |
OptimisedRoute 53Steps 5 · Total yield /
(I)101438-36-a27548-93-2(II)101438-36-a204124-97-0(III)101438-36-a99528-64-0(IV)101438-36-a436083-31-7(V)101438-36-a436083-32-8(VI)101438-36-a133524-70-6(VII)101438-36-a98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-36-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-36-a | 204124-97-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-1,13-dihydroxy-9-oxo-7-(2,2,2-trichloroacetoxy)-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-36-a | 99528-64-0 | (2R,3R)-3-phenyloxirane-2-carboxylic acid |
| (IV)101438-36-a | 436083-31-7 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(2,2,2-trichloroacetyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (2R,3R)-3-phenyloxirane-2-carboxylate |
| (V)101438-36-a | 436083-32-8 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-azido-2-hydroxy-3-phenylpropanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VI)101438-36-a | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (VII)101438-36-a | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 54Steps 4 · Total yield /
(I)101438-37-a103-36-6(II)101438-37-a108741-14-6(III)101438-37-a271243-44-8(IV)101438-37-a136561-53-0(V)101438-37-a132201-33-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-37-a | 103-36-6 | 3-Phenyl-2-propenoic acid ethyl ester |
| (II)101438-37-a | 108741-14-6 | ethyl (2R,3S)-2,3-dihydroxy-3-phenylpropanoate |
| (III)101438-37-a | 271243-44-8 | ethyl (4S,5R)-3-benzoyl-2-oxo-4-phenyl-1,3-oxazolidine-5-carboxylate |
| (IV)101438-37-a | 136561-53-0 | (2R,3S)-3-Amino-2-hydroxy-3-phenylpropanoic acid |
| (V)101438-37-a | 132201-33-3 | (2R,3S)-2-Hydroxy-3-phenyl-3-(phenylformamido)propanoic acid |
OptimisedRoute 55Steps 3 · Total yield /
(I)101438-38-a100-58-3(III)101438-38-a—(IV)101438-38-a88-95-9(V)101438-38-a128592-81-4(VI)101438-38-a133524-70-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-38-a | 100-58-3 | Bromo(phenyl)magnesium |
| (III)101438-38-a | - | [C11]Benzoic acid |
| (IV)101438-38-a | 88-95-9 | ortho-Phthaloyl chloride |
| (V)101438-38-a | 128592-81-4 | [11C]Benzoyl chloride |
| (VI)101438-38-a | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 56Steps 8 · Total yield /
(I)101438-39-a136561-53-0(II)101438-39-a35718-08-2(III)101438-39-a452304-81-3(IV)101438-39-a452304-82-4(IX)101438-39-a452304-85-7(V)101438-39-a116-11-0(VI)101438-39-a452304-83-5(VII)101438-39-a452304-84-6(VIII)101438-39-a103150-33-0(X)101438-39-a114915-15-0(XI)101438-39-a98-88-4(XII)101438-39-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-39-a | 136561-53-0 | (2R,3S)-3-Amino-2-hydroxy-3-phenylpropanoic acid |
| (II)101438-39-a | 35718-08-2 | chloro(prop-2-yn-1-yloxy)methanone |
| (III)101438-39-a | 452304-81-3 | (2R,3S)-2-hydroxy-3-phenyl-3-{[(prop-2-yn-1-yloxy)carbonyl]amino}propanoic acid |
| (IV)101438-39-a | 452304-82-4 | methyl (2R,3S)-2-hydroxy-3-phenyl-3-{[(prop-2-yn-1-yloxy)carbonyl]amino}propanoate |
| (IX)101438-39-a | 452304-85-7 | 5-(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl 3-prop-2-yn-1-yl (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (V)101438-39-a | 116-11-0 | 2-Methoxy-1-propene |
| (VI)101438-39-a | 452304-83-5 | 5-methyl 3-prop-2-yn-1-yl (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (VII)101438-39-a | 452304-84-6 | (4S,5R)-2,2-dimethyl-4-phenyl-3-[(prop-2-yn-1-yloxy)carbonyl]-1,3-oxazolidine-5-carboxylic acid |
| (VIII)101438-39-a | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (X)101438-39-a | 114915-15-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XI)101438-39-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (XII)101438-39-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-1,4-dihydroxy-15-{[(2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoyl]oxy}-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 57Steps 2 · Total yield /
(I)101438-40-a205514-11-0(II)101438-40-a133524-70-6(III)101438-40-a98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-40-a | 205514-11-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy}-9-{[(benzyloxy)carbonyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (II)101438-40-a | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-40-a | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 58Steps 3 · Total yield /
(I)101438-41-a205514-11-0(II)101438-41-a379688-64-9(III)101438-41-a838-58-4(IV)101438-41-a186358-04-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-41-a | 205514-11-0 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy}-9-{[(benzyloxy)carbonyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (II)101438-41-a | 379688-64-9 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-3-amino-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-41-a | 838-58-4 | 1-phenylethenyl benzoate |
| (IV)101438-41-a | 186358-04-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-{[(2R,3S)-2-[(benzyloxy)methoxy]-3-phenyl-3-(phenylformamido)propanoyl]oxy}-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
OptimisedRoute 59Steps 2 · Total yield /
(I)101438-42-a124649-67-8(II)101438-42-a100-47-0(III)101438-42-a146848-91-1(IV)101438-42-a132201-33-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-42-a | 124649-67-8 | methyl (2S,3R)-2,3-dihydroxy-3-phenylpropanoate |
| (II)101438-42-a | 100-47-0 | Benzonitrile |
| (III)101438-42-a | 146848-91-1 | methyl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylate |
| (IV)101438-42-a | 132201-33-3 | (2R,3S)-2-Hydroxy-3-phenyl-3-(phenylformamido)propanoic acid |
OptimisedRoute 60Steps 5 · Total yield /
(I)101438-43-a32981-86-5(II)101438-43-a108-24-7(III)101438-43-a27548-93-2(IV)101438-43-a103150-33-0(V)101438-43-a149249-91-2(VI)101438-43-a219780-99-1API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-43-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-43-a | 108-24-7 | Acetic acid acetic anhydride |
| (III)101438-43-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-43-a | 103150-33-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,13-dihydroxy-9-oxo-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (V)101438-43-a | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (VI)101438-43-a | 219780-99-1 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 61Steps 5 · Total yield /
(I)101438-44-a—(II)101438-44-a160582-74-1(III)101438-44-a160582-75-2(IV)101438-44-a115437-21-3(V)101438-44-a149249-91-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-44-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,15-bis[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (II)101438-44-a | 160582-74-1 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-1-[(dimethylsilyl)oxy]-10,14,17,17-tetramethyl-11-oxo-9,15-bis[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-44-a | 160582-75-2 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-1-[(dimethylsilyl)oxy]-4-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,15-bis[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-44-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (V)101438-44-a | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
OptimisedRoute 62Steps 3 · Total yield /
(I)101438-45-a189006-03-9(II)101438-45-a115437-21-3(III)101438-45-a244760-98-3(IV)101438-45-a906370-55-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-45-a | 189006-03-9 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-1,4,9,15-tetrahydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (II)101438-45-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-45-a | 244760-98-3 | (4S,5R)-3-benzoyl-2-methoxy-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (IV)101438-45-a | 906370-55-6 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-3-benzoyl-2-methoxy-4-phenyl-1,3-oxazolidine-5-carboxylate |
OptimisedRoute 63Steps 7 · Total yield /
(I)101438-46-a142203-65-4(II)101438-46-a162475-68-5(III)101438-46-a911107-32-9(IV)101438-46-a911107-33-0(IX)101438-46-a98-88-4(V)101438-46-a—(VI)101438-46-a—(VII)101438-46-a—(VIII)101438-46-a133524-70-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-46-a | 142203-65-4 | 13-Acetyl-9-dihydrobaccatin-III |
| (II)101438-46-a | 162475-68-5 | (2alpha,5beta,7beta,9beta,10beta,13alpha)-4-(Acetyloxy)-1,7,9,10,13-pentahydroxy-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-46-a | 911107-32-9 | (1S,2S,3R,4S,7R,9S,10R,11R,12R,15S)-4-(acetyloxy)-9-[(tert-butyldimethylsilyl)oxy]-1,11,12,15-tetrahydroxy-10,14,17,17-tetramethyl-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-46-a | 911107-33-0 | (1S,2S,3R,4S,7R,9S,10R,11R,12R,15S)-4,12-bis(acetyloxy)-9-[(tert-butyldimethylsilyl)oxy]-1,11,15-trihydroxy-10,14,17,17-tetramethyl-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IX)101438-46-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (V)101438-46-a | - | (4S,5R)-3-[(tert-butoxy)carbonyl]-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (VI)101438-46-a | - | 5-(1S,2S,3R,4S,7R,9S,10R,11R,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-9-[(tert-butyldimethylsilyl)oxy]-1,11-dihydroxy-10,14,17,17-tetramethyl-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl 3-tert-butyl (4S,5R)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (VII)101438-46-a | - | 5-(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-9-[(tert-butyldimethylsilyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl 3-tert-butyl (4S,5R)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (VIII)101438-46-a | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 64Steps 6 · Total yield /
(I)101438-47-a124605-42-1(II)101438-47-a33250-32-7(III)101438-47-a1033962-75-2(IV)101438-47-a1033962-60-5(IX)101438-47-a—(V)101438-47-a204124-97-0(VI)101438-47-a32981-86-5(VII)101438-47-a76-02-8(VIII)101438-47-a506-96-7(X)101438-47-a1033962-70-7(XI)101438-47-a98-88-4(XII)101438-47-a1033962-72-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-47-a | 124605-42-1 | 3(S)-(tert-Butoxycarbonylamino)-2(R)-hydroxy-3-phenylpropionic acid methyl ester |
| (II)101438-47-a | 33250-32-7 | 1-(Dimethoxymethyl)naphthalene |
| (III)101438-47-a | 1033962-75-2 | (2R,4S,5R)-2-(Naphthalen-1-yl)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylic acid 3-tert-butyl 5-methyl ester |
| (IV)101438-47-a | 1033962-60-5 | (2R,4S,5R)-3-[(Tert-butoxy)carbonyl]-2-(naphthalen-1-yl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (IX)101438-47-a | - | - |
| (V)101438-47-a | 204124-97-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-1,13-dihydroxy-9-oxo-7-(2,2,2-trichloroacetoxy)-5,20-epoxytax-11-en-2-yl benzoate |
| (VI)101438-47-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (VII)101438-47-a | 76-02-8Available | 2,2,2-Tris(chloranyl)ethanoyl chloride |
| (VIII)101438-47-a | 506-96-7 | Acetic acid bromide |
| (X)101438-47-a | 1033962-70-7 | - |
| (XI)101438-47-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (XII)101438-47-a | 1033962-72-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-(2,2,2-trichloroacetoxy)-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 65Steps 4 · Total yield /
(I)101438-48-a142203-65-4(II)101438-48-a351885-33-1(III)101438-48-a945480-76-2(IV)101438-48-a183743-19-3(Va)101438-48-a216094-54-1(Vb)101438-48-a201856-53-3(VI)101438-48-a,(VI)101438-48-b—(VII)101438-48-b—(VIII)101438-48-b115437-19-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-48-a | 142203-65-4 | 13-Acetyl-9-dihydrobaccatin-III |
| (II)101438-48-a | 351885-33-1 | (2aR,4S,4aR,5R,6R,9S,11S,12S,12aR,12bS)-9,12b-Bis(acetoxy)-5,6,11-trihydroxy-4a,8,13,13-tetramethyl-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (III)101438-48-a | 945480-76-2 | (2aR,4S,4aS,9S,11S,12S,12aR,12bS)-9,12b-Bis(acetoxy)-11-hydroxy-4a,8,13,13-tetramethyl-5,6-dioxo-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (IV)101438-48-a | 183743-19-3 | (2aR,4S,4aS,9S,11S,12S,12aR,12bS)-12b-(Acetoxy-9,11-dihydroxy-4a,8,13,13-tetramethyl-5,6-dioxo-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (Va)101438-48-a | 216094-54-1 | 3(S)-(Benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropionic acid |
| (Vb)101438-48-a | 201856-53-3 | 1-Benzoyl-3(R)-(1-ethoxyethoxy)-4(S)-phenylazetidin-2-one |
| (VI)101438-48-a,(VI)101438-48-b | - | (2aR,4S,4aS,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-9-[3(S)-(benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropanoyloxy]-11-hydroxy-4a,8,13,13-tetramethyl-5,6-dioxo-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (VII)101438-48-b | - | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetoxy)-9-[3(S)-(benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropanoyloxy]-6,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (VIII)101438-48-b | 115437-19-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 66Steps 3 · Total yield /
(VI)101438-48-a,(VI)101438-48-b—(VII)101438-48-b—(VIII)101438-48-b115437-19-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (VI)101438-48-a,(VI)101438-48-b | - | (2aR,4S,4aS,9S,11S,12S,12aR,12bS)-12b-(Acetyloxy)-9-[3(S)-(benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropanoyloxy]-11-hydroxy-4a,8,13,13-tetramethyl-5,6-dioxo-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (VII)101438-48-b | - | (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-12b-(Acetoxy)-9-[3(S)-(benzamido)-2(R)-(1-ethoxyethoxy)-3-phenylpropanoyloxy]-6,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-4-[triethylsilyloxy]-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl benzoate |
| (VIII)101438-48-b | 115437-19-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-(1-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 67Steps 5 · Total yield /
(I)101438-50-a2835-06-5(II)101438-50-a98-88-4(III)101438-50-a29670-63-1(IV)101438-50-a4755-77-5(V)101438-50-a167095-12-7(VI)101438-50-a153433-79-5(VII)101438-50-a—(VIII)101438-50-a132201-33-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-50-a | 2835-06-5 | (±)-alpha-Aminophenylacetic acid |
| (II)101438-50-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (III)101438-50-a | 29670-63-1 | 2-Phenyl-2-(phenylformamido)acetic acid |
| (IV)101438-50-a | 4755-77-5 | 1-(Chlorocarbonyl)formic acid ethyl ester |
| (V)101438-50-a | 167095-12-7 | (1E)-3-Ethoxy-3-oxo-1-phenyl-1-[(phenylcarbonyl)amino]prop-1-en-2-yl ethyl ethanedioate |
| (VI)101438-50-a | 153433-79-5 | Ethyl 2-oxo-3-phenyl-3-[(phenylcarbonyl)amino]propanoate |
| (VII)101438-50-a | - | (±)-Ethyl (2R,3S)-2-hydroxy-3-phenyl-3-[(phenylcarbonyl)amino]propanoate |
| (VIII)101438-50-a | 132201-33-3 | (2R,3S)-2-Hydroxy-3-phenyl-3-(phenylformamido)propanoic acid |
OptimisedRoute 68Steps 3 · Total yield /
(I)101438-51-a78432-77-6(II)101438-51-a155556-72-2(III)101438-51-a108-24-7(IV)101438-51-a135365-62-7API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-51-a | 78432-77-6 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy]-1,7,10-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-51-a | 155556-72-2 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,10-dihydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-51-a | 108-24-7 | Acetic acid acetic anhydride |
| (IV)101438-51-a | 135365-62-7 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 69Steps 5 · Total yield /
(I)101438-52-a32981-86-5(II)101438-52-a27548-93-2(III)101438-52-a204124-97-0(IV)101438-52-a949023-16-9(V)101438-52-a—(VI)101438-52-a1033962-72-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-52-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-52-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-52-a | 204124-97-0 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-1,13-dihydroxy-9-oxo-7-(2,2,2-trichloroacetoxy)-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-52-a | 949023-16-9 | (4S,5R)-3-Benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (V)101438-52-a | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-2-(benzoyloxy)-1-hydroxy-9-oxo-7-(2,2,2-trichloroacetoxy)-5,20-epoxytax-11-en-13-yl (4S,5R)-3-benzoyl-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate |
| (VI)101438-52-a | 1033962-72-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Diacetoxy-13-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-(2,2,2-trichloroacetoxy)-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 70Steps 4 · Total yield /
(I)101438-53-a190730-58-6(II)101438-53-a190730-59-7(III)101438-53-a190847-56-4(IV)101438-53-a77877-20-4(V)101438-53-a190730-60-0(VI)101438-53-a190730-64-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-53-a | 190730-58-6 | (4R,5S)-3-[(3R)-4-Bromo-3-[[tert-butyl(dimethyl)silyl]oxy]pent-4-enoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one |
| (II)101438-53-a | 190730-59-7 | (3R)-4-Bromo-3-[[tert-butyl(dimethyl)silyl]oxy]pent-4-en-1-ol |
| (III)101438-53-a | 190847-56-4 | (3R)-4-Bromo-3-[[tert-butyl(dimethyl)silyl]oxy]pent-4-enal |
| (IV)101438-53-a | 77877-20-4 | (4R,5S)-4-methyl-5-phenyl-3-propanoyl-1,3-oxazolidin-2-one |
| (V)101438-53-a | 190730-60-0 | (4R,5S)-3-[(2R,3S,5R)-6-Bromo-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-2-methylhept-6-enoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one |
| (VI)101438-53-a | 190730-64-4 | (2R,3S,5R)-6-Bromo-5-[[tert-butyl(dimethyl)silyl]oxy]-3-hydroxy-2-methylhept-6-enoic acid |
OptimisedRoute 71Steps 12 · Total yield /
(I)101438-54-a97-62-1(II)101438-54-a106-96-7(III)101438-54-a107540-02-3(IV)101438-54-a86101-48-6(IX)101438-54-a503-60-6(V)101438-54-a1612868-59-3(VI)101438-54-a6638-79-5(VII)101438-54-a1612868-72-0(VIII)101438-54-a35189-96-9(X)101438-54-a1612868-73-1(XI)101438-54-a7677-24-9(XII)101438-54-a1612868-74-2(XIII)101438-54-a1612868-75-3(XIV)101438-54-a—(XIX)101438-54-a—(XV)101438-54-a1612868-93-5(XVI)101438-54-a1612868-95-7(XVII)101438-54-a1612868-97-9(XVIII)101438-54-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-54-a | 97-62-1 | 2-Methylpropionic acid ethyl ester |
| (II)101438-54-a | 106-96-7 | 2-Propynyl bromide |
| (III)101438-54-a | 107540-02-3 | Ethyl 2,2-dimethylpent-4-ynoate |
| (IV)101438-54-a | 86101-48-6 | 2,2-Dimethylpent-4-ynoic acid |
| (IX)101438-54-a | 503-60-6 | 1-Chloro-3-methyl-2-butene |
| (V)101438-54-a | 1612868-59-3 | 2,2-Dimethylpent-3-ynoic acid |
| (VI)101438-54-a | 6638-79-5Available | N-Methoxy-N-methylamine hydrochloride |
| (VII)101438-54-a | 1612868-72-0 | N-Methoxy-N,2,2-trimethylpent-3-ynamide |
| (VIII)101438-54-a | 35189-96-9 | chloro(3-methylbut-2-en-1-yl)magnesium |
| (X)101438-54-a | 1612868-73-1 | 2,6,6-Trimethylnon-2-en-7-yn-5-one |
| (XI)101438-54-a | 7677-24-9 | Cyanotrimethylsilane |
| (XII)101438-54-a | 1612868-74-2 | 5-Methyl-2-(2-methylpent-3-yn-2-yl)-2-[(trimethylsilyl)oxy]hex-4-enenitrile |
| (XIII)101438-54-a | 1612868-75-3 | 5-Methyl-2-(2-methylpent-3-yn-2-yl)-2-[(trimethylsilyl)oxy]hex-4-enal |
| (XIV)101438-54-a | - | (2E)-1-[1,1,1,3,3,3-Hexamethyl-2-(trimethylsilyl)trisilan-2-yl]-2-[(2S)-2-methyl-2-[3-(trityloxy)propyl]cyclohexylidene]hydrazine |
| (XIX)101438-54-a | - | (3aS,7Z,9aS,13bS)-6,9a,14,14-Tetramethyl-9,9a,10,11,12,13b-hexahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XV)101438-54-a | 1612868-93-5 | (1S,2S)-5-Methyl-2-(2-methylpent-3-yn-2-yl)-1-[(6S)-6-methyl-6-[3-(trityloxy)propyl]cyclohex-1-en-1-yl]hex-4-ene-1,2-diol |
| (XVI)101438-54-a | 1612868-95-7 | (4S,5S)-4-(3-Methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-5-[(6S)-6-methyl-6-[3-(trityloxy)propyl]cyclohex-1-en-1-yl]-1,3-dioxolan-2-one |
| (XVII)101438-54-a | 1612868-97-9 | (4S,5S)-5-[(6S)-6-(3-Hydroxypropyl)-6-methylcyclohex-1-en-1-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
| (XVIII)101438-54-a | - | (4S)-5-[(6S)-6-Allyl-6-methylcyclohex-1-en-1-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
OptimisedRoute 72Steps 14 · Total yield /
(I)101438-55-a2873-29-2(II)101438-55-a20701-51-3(III)101438-55-a64551-84-4(IV)101438-55-a61278-06-6(IX)101438-55-a326922-32-1(V)101438-55-a21317-49-7(VI)101438-55-a1782938-32-2(VII)101438-55-a—(VIII)101438-55-a1782938-44-6(X)101438-55-a917-54-4(XI)101438-55-a326922-33-2(XII)101438-55-a326922-34-3(XIII)101438-55-a65032-27-1(XIV)101438-55-a50-00-0(XV)101438-55-a326922-35-4(XVI)101438-55-a326922-37-6(XVII)101438-55-a—(XVIII)101438-55-a,(XVIII)101438-55-b—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-55-a | 2873-29-2 | (2R,3S,4R)-3,4-Diacetoxy-3,4-dihydro-2H-pyran-2-yl]methyl acetate |
| (II)101438-55-a | 20701-51-3 | Methyl 4,6-di-O-acetyl-2,3-dideoxy-alpha-D-erythro-hex-2-enopyranoside |
| (III)101438-55-a | 64551-84-4 | Methyl 4,6-di-O-acetyl-2,3-dideoxy-alpha-D-erythro-hexopyranoside |
| (IV)101438-55-a | 61278-06-6 | Methyl 2,3-dideoxy-alpha-D-erythro-hexopyranoside |
| (IX)101438-55-a | 326922-32-1 | (6S)-6-(Benzyloxy)cyclohex-2-en-1-one |
| (V)101438-55-a | 21317-49-7 | (2S,3S,6S)-2-(Iodomethyl)-6-methoxytetrahydro-2H-pyran-3-ol |
| (VI)101438-55-a | 1782938-32-2 | (2S,3S,6S)-3-(Benzyloxy)-2-(iodomethyl)-6-methoxytetrahydro-2H-pyran |
| (VII)101438-55-a | - | (3S,6S)-3-(Benzyloxy)-6-methoxy-2-methylenetetrahydro-2H-pyran |
| (VIII)101438-55-a | 1782938-44-6 | (2S,5R)-2-(Benzyloxy)-5-hydroxycyclohexanone |
| (X)101438-55-a | 917-54-4 | lithium carbanide |
| (XI)101438-55-a | 326922-33-2 | (6S)-6-(Benzyloxy)-1-methylcyclohex-2-en-1-ol |
| (XII)101438-55-a | 326922-34-3 | (4S)-4-(Benzyloxy)-3-methylcyclohex-2-en-1-one |
| (XIII)101438-55-a | 65032-27-1 | Chloro(ethynyl)magnesium |
| (XIV)101438-55-a | 50-00-0Available | Formaldehyde |
| (XV)101438-55-a | 326922-35-4 | (2R,3S,4S)-4-(Benzyloxy)-2-(hydroxymethyl)-3-methyl-3-vinylcyclohexanone |
| (XVI)101438-55-a | 326922-37-6 | (2R,3S,4S)-4-(Benzyloxy)-3-methyl-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-vinylcyclohexanone |
| (XVII)101438-55-a | - | (1S,2R,3S,4S)-4-(Benzyloxy)-3-methyl-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]-3-vinylcyclohexanol |
| (XVIII)101438-55-a,(XVIII)101438-55-b | - | 2-[[(1R,2S,3S,6S)-3-(Benzyloxy)-6-(methoxymethoxy)-2-methyl-2-vinylcyclohexyl]methoxy]tetrahydro-2H-pyran |
OptimisedRoute 73Steps 9 · Total yield /
(XXVI)101438-55-b1782938-10-6(XX)101438-55-b—(XXIX)101438-55-b,(XXIX)101438-55-c1782938-16-2(XXII)101438-55-b1782937-94-3(XXVIII)101438-55-b1782938-12-8(XXIV)101438-55-b1782938-08-2(XXV)101438-55-b1782938-09-3(XXI)101438-55-b1782938-41-3(XIX)101438-55-b—(XVIII)101438-55-a,(XVIII)101438-55-b—(XXIII)101438-55-b,(XXIII)101438-55-d—(XXVII)101438-55-b32315-10-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXVI)101438-55-b | 1782938-10-6 | (1S)-1-[(S)-[(1R,2S,3S,6S)-3-(Benzyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexyl](hydroxy)methyl]-2,2,4-trimethylcyclohex-3-en-1-ol |
| (XX)101438-55-b | - | (2-[(1S,2R,3S,6S)-6-(Benzyloxy)-3-(methoxymethoxy)-1-methyl-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclohexyl]ethoxy)(tert-butyl)diphenylsilane |
| (XXIX)101438-55-b,(XXIX)101438-55-c | 1782938-16-2 | (1S,2S,3S,4S)-2-(2-[[tert-Butyl(diphenyl)silyl]oxy]ethyl)-4-(methoxymethoxy)-2-methyl-3-[(4S,5S)-6,6,8-trimethyl-2,9-dioxo-1,3-dioxaspiro[4.5]dec-7-en-4-yl]cyclohexyl benzoate |
| (XXII)101438-55-b | 1782937-94-3 | (1S,2S,3S,6S)-3-(Benzyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexanecarbaldehyde |
| (XXVIII)101438-55-b | 1782938-12-8 | (4S,5S)-4-[(1S,2S,3S,6S)-3-(Benzyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexyl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
| (XXIV)101438-55-b | 1782938-08-2 | (S)-[(1R,2S,3S,6S)-3-(Benzyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexyl](4,6,6-trimethylcyclohexa-1,4-dien-1-yl)methanol |
| (XXV)101438-55-b | 1782938-09-3 | (S)-[(1R,2S,3S,6S)-3-(Benzyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexyl][(1S,6S)-2,2,4-trimethyl-7-oxabicyclo[4.1.0]hept-3-en-1-yl]methanol |
| (XXI)101438-55-b | 1782938-41-3 | [(1R,2S,3S,6S)-3-(Benzyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexyl]methanol |
| (XIX)101438-55-b | - | 2-[(1S,2R,3S,6S)-6-(Benzyloxy)-3-(methoxymethoxy)-1-methyl-2-[(tetrahydro-2H-pyran-2-yloxy)methyl]cyclohexyl]ethanol |
| (XVIII)101438-55-a,(XVIII)101438-55-b | - | 2-[[(1R,2S,3S,6S)-3-(Benzyloxy)-6-(methoxymethoxy)-2-methyl-2-vinylcyclohexyl]methoxy]tetrahydro-2H-pyran |
| (XXIII)101438-55-b,(XXIII)101438-55-d | - | 2,4,6-Triisopropyl-N'-[(1Z)-2,2,4-trimethylcyclohex-3-en-1-ylidene]benzenesulfonohydrazide |
| (XXVII)101438-55-b | 32315-10-9 | Bis(trichloromethyl) carbonate |
OptimisedRoute 74Steps 4 · Total yield /
(XXIX)101438-55-b,(XXIX)101438-55-c1782938-16-2(XXX)101438-55-c1782938-51-5(XXXI)101438-55-c1782938-52-6(XXXII)101438-55-c1782938-53-7(XXXIII)101438-55-c—(XXXIV)101438-55-c—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXIX)101438-55-b,(XXIX)101438-55-c | 1782938-16-2 | (1S,2S,3S,4S)-2-(2-[[tert-Butyl(diphenyl)silyl]oxy]ethyl)-4-(methoxymethoxy)-2-methyl-3-[(4S,5S)-6,6,8-trimethyl-2,9-dioxo-1,3-dioxaspiro[4.5]dec-7-en-4-yl]cyclohexyl benzoate |
| (XXX)101438-55-c | 1782938-51-5 | (1S,2S,3S,4S)-2-(2-[[tert-Butyl(diphenyl)silyl]oxy]ethyl)-3-[(4S,5S,9R)-9-hydroxy-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-4-yl]-4-(methoxymethoxy)-2-methylcyclohexyl benzoate |
| (XXXI)101438-55-c | 1782938-52-6 | (4S,5S,7R)-4-[(1S,2S,3S,6S)-3-(Benzoyloxy)-2-(2-[[tert-butyl(diphenyl)silyl]oxy]ethyl)-6-(methoxymethoxy)-2-methylcyclohexyl]-8,10,10-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-8-en-7-yl benzoate |
| (XXXII)101438-55-c | 1782938-53-7 | (4S,5S,7R)-4-[(1S,2S,3S,6S)-3-(Benzoyloxy)-2-(2-hydroxyethyl)-6-(methoxymethoxy)-2-methylcyclohexyl]-8,10,10-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-8-en-7-yl benzoate |
| (XXXIII)101438-55-c | - | (4S,5S)-4-[(1S,2S,3S,6S)-3-(Benzoyloxy)-6-(methoxymethoxy)-2-methyl-2-(2-oxoethyl)cyclohexyl]-8,10,10-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-8-en-7-yl benzoate |
| (XXXIV)101438-55-c | - | (3aS,7S,8R,9aS,10S,13S,13aS,13bS)-8-Hydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
OptimisedRoute 75Steps 6 · Total yield /
(XXXVIII)101438-55-d126-30-7(XXXVII)101438-55-d562-13-0(XLIII)101438-55-d87128-98-1(XXIII)101438-55-b,(XXIII)101438-55-d—(XLIV)101438-55-d39085-59-1(XXXIX)101438-55-d75072-38-7(XLII)101438-55-d188569-79-1(XXXV)101438-55-d504-02-9(XLI)101438-55-d1085255-37-3(XL)101438-55-d1576-35-8(XXXVI)101438-55-d74-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXXVIII)101438-55-d | 126-30-7 | 1,3-Dihydroxy-2,2-dimethylpropane |
| (XXXVII)101438-55-d | 562-13-0 | 2,2-Dimethylcyclohexane-1,3-dione |
| (XLIII)101438-55-d | 87128-98-1 | 2,2,4-Trimethylcyclohex-3-en-1-one |
| (XXIII)101438-55-b,(XXIII)101438-55-d | - | 2,4,6-Triisopropyl-N'-[(1Z)-2,2,4-trimethylcyclohex-3-en-1-ylidene]benzenesulfonohydrazide |
| (XLIV)101438-55-d | 39085-59-1 | 2,4,6-Triisopropylbenzenesulfonohydrazide |
| (XXXIX)101438-55-d | 75072-38-7 | 3,3,7,7-Tetramethyl-1,5-dioxaspiro[5.5]undecan-8-one |
| (XLII)101438-55-d | 188569-79-1 | 3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-ene |
| (XXXV)101438-55-d | 504-02-9 | 3,5-Cyclohexanedione |
| (XLI)101438-55-d | 1085255-37-3 | 4-Methyl-N'-[(8E)-3,3,7,7-tetramethyl-1,5-dioxaspiro[5.5]undec-8-ylidene]benzenesulfonohydrazide |
| (XL)101438-55-d | 1576-35-8 | 4-Methylbenzenesulfonhydrazide |
| (XXXVI)101438-55-d | 74-88-4Available | Iodomethane |
OptimisedRoute 76Steps 11 · Total yield /
(I)101438-56-a—(II)101438-56-a—(III)101438-56-a—(IV)101438-56-a—(IX)101438-56-a1782958-95-5(V)101438-56-a—(VI)101438-56-a—(VII)101438-56-a1782958-93-3(VIII)101438-56-a1782958-94-4(X)101438-56-a13170-43-9(XI)101438-56-a1782958-96-6(XII)101438-56-a1782959-01-6(XIII)101438-56-a,(XIII)101438-56-b1782958-97-7API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-56-a | - | (3aS,7S,8R,9aS,10S,13S,13aS,13bS)-8-Hydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (II)101438-56-a | - | (3aS,7S,9aS,10S,13S,13aS,13bS)-13-(Methoxymethoxy)-6,9a,14,14-tetramethyl-2,8-dioxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (III)101438-56-a | - | (3aS,7S,8S,9aS,10S,13S,13aS,13bS)-8-Hydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (IV)101438-56-a | - | (3aS,7S,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (IX)101438-56-a | 1782958-95-5 | (3aS,8S,9aS,10S,13aR,13bS)-8-(Benzyloxy)-6,9a,14,14-tetramethyl-2,13-dioxo-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (V)101438-56-a | - | (3aS,5R,6S,7S,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-5,6-dihydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxododecahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (VI)101438-56-a | - | (3aS,5R,6S,7S,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-5,6-bis[[(methylsulfanyl)carbonothioyl]oxy]-2-oxododecahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (VII)101438-56-a | 1782958-93-3 | (3aS,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (VIII)101438-56-a | 1782958-94-4 | (3aS,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-hydroxy-6,9a,14,14-tetramethyl-2-oxo-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (X)101438-56-a | 13170-43-9 | Chloro[(trimethylsilyl)methyl]magnesium |
| (XI)101438-56-a | 1782958-96-6 | (3aS,8S,9aS,10S,13R,13aR,13bS)-8-(Benzyloxy)-13-hydroxy-6,9a,14,14-tetramethyl-2-oxo-13-[(trimethylsilyl)methyl]-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (XII)101438-56-a | 1782959-01-6 | (3aS,8S,9aS,10S,13R,13aR,13bS)-8,13-Dihydroxy-6,9a,14,14-tetramethyl-2-oxo-13-[(trimethylsilyl)methyl]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (XIII)101438-56-a,(XIII)101438-56-b | 1782958-97-7 | (3aS,9aS,10S,13R,13aR,13bS)-13-Hydroxy-6,9a,14,14-tetramethyl-2,8-dioxo-13-[(trimethylsilyl)methyl]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
OptimisedRoute 77Steps 7 · Total yield /
(XIII)101438-56-a,(XIII)101438-56-b1782958-97-7(IX)101438-56-a1782958-95-5(XI)101438-56-a1782958-96-6(XII)101438-56-a1782959-01-6(VII)101438-56-a1782958-93-3(VIII)101438-56-a1782958-94-4(VI)101438-56-a—(V)101438-56-a—(I)101438-56-a—(IV)101438-56-a—(III)101438-56-a—(II)101438-56-a—(X)101438-56-a13170-43-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIII)101438-56-a,(XIII)101438-56-b | 1782958-97-7 | (3aS,9aS,10S,13R,13aR,13bS)-13-Hydroxy-6,9a,14,14-tetramethyl-2,8-dioxo-13-[(trimethylsilyl)methyl]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (IX)101438-56-a | 1782958-95-5 | (3aS,8S,9aS,10S,13aR,13bS)-8-(Benzyloxy)-6,9a,14,14-tetramethyl-2,13-dioxo-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (XI)101438-56-a | 1782958-96-6 | (3aS,8S,9aS,10S,13R,13aR,13bS)-8-(Benzyloxy)-13-hydroxy-6,9a,14,14-tetramethyl-2-oxo-13-[(trimethylsilyl)methyl]-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (XII)101438-56-a | 1782959-01-6 | (3aS,8S,9aS,10S,13R,13aR,13bS)-8,13-Dihydroxy-6,9a,14,14-tetramethyl-2-oxo-13-[(trimethylsilyl)methyl]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (VII)101438-56-a | 1782958-93-3 | (3aS,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (VIII)101438-56-a | 1782958-94-4 | (3aS,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-hydroxy-6,9a,14,14-tetramethyl-2-oxo-9,9a,10,11,12,13,13a,13b-octahydro-8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (VI)101438-56-a | - | (3aS,5R,6S,7S,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-5,6-bis[[(methylsulfanyl)carbonothioyl]oxy]-2-oxododecahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (V)101438-56-a | - | (3aS,5R,6S,7S,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-5,6-dihydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxododecahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (I)101438-56-a | - | (3aS,7S,8R,9aS,10S,13S,13aS,13bS)-8-Hydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (IV)101438-56-a | - | (3aS,7S,8S,9aS,10S,13S,13aS,13bS)-8-(Benzyloxy)-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (III)101438-56-a | - | (3aS,7S,8S,9aS,10S,13S,13aS,13bS)-8-Hydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (II)101438-56-a | - | (3aS,7S,9aS,10S,13S,13aS,13bS)-13-(Methoxymethoxy)-6,9a,14,14-tetramethyl-2,8-dioxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (X)101438-56-a | 13170-43-9 | Chloro[(trimethylsilyl)methyl]magnesium |
OptimisedRoute 78Steps 9 · Total yield /
(I)101438-57-a100-84-5(II)101438-57-a13697-84-2(III)101438-57-a83313-55-7(IV)101438-57-a1193-18-6(IX)101438-57-a3536-96-7(V)101438-57-a,(V)101438-57-b83515-96-2(VI)101438-57-a1916469-78-7(VII)101438-57-a1916469-81-2(VIII)101438-57-a,(VIII)101438-57-b326922-34-3(X)101438-57-a1800048-14-9(XI)101438-57-a326922-35-4(XII)101438-57-a326922-36-5API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-57-a | 100-84-5 | 1-Methoxy-3-methylbenzene |
| (II)101438-57-a | 13697-84-2 | 1-Methoxy-5-methyl-1,4-cyclohexadiene |
| (III)101438-57-a | 83313-55-7 | 7-Methyl-1,4-dioxaspiro[4.5]dec-7-ene |
| (IV)101438-57-a | 1193-18-6 | 3-Methyl-2-cyclohexen-1-one |
| (IX)101438-57-a | 3536-96-7 | Chlorido(ethenyl)magnesium |
| (V)101438-57-a,(V)101438-57-b | 83515-96-2 | (±)-7-Methyl-1,4-dioxaspiro[4.5]decane-7,8-diol |
| (VI)101438-57-a | 1916469-78-7 | (-)-(7R,8S)-7-Methyl-1,4-dioxaspiro[4.5]decane-7,8-diol |
| (VII)101438-57-a | 1916469-81-2 | (7R,8S)-8-(Benzyloxy)-7-methyl-1,4-dioxaspiro[4.5]decan-7-ol |
| (VIII)101438-57-a,(VIII)101438-57-b | 326922-34-3 | (4S)-4-(Benzyloxy)-3-methylcyclohex-2-en-1-one |
| (X)101438-57-a | 1800048-14-9 | [[(3S,4S)-4-(Benzyloxy)-3-ethenyl-3-methylcyclohex-1-en-1-yl]oxy](trimethyl)silane |
| (XI)101438-57-a | 326922-35-4 | (2R,3S,4S)-4-(Benzyloxy)-2-(hydroxymethyl)-3-methyl-3-vinylcyclohexanone |
| (XII)101438-57-a | 326922-36-5 | (2S,3S,4S)-4-(Benzyloxy)-3-ethenyl-2-(hydroxymethyl)-3-methylcyclohexanone |
OptimisedRoute 79Steps 6 · Total yield /
(V)101438-57-a,(V)101438-57-b83515-96-2(VIII)101438-57-a,(VIII)101438-57-b326922-34-3(XIII)101438-57-b1916469-80-1(XIV)101438-57-b1916469-82-3(XV)101438-57-b1916469-83-4(XVI)101438-57-b1916469-84-5(XVII)101438-57-b1916469-85-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (V)101438-57-a,(V)101438-57-b | 83515-96-2 | (±)-7-Methyl-1,4-dioxaspiro[4.5]decane-7,8-diol |
| (VIII)101438-57-a,(VIII)101438-57-b | 326922-34-3 | (4S)-4-(Benzyloxy)-3-methylcyclohex-2-en-1-one |
| (XIII)101438-57-b | 1916469-80-1 | (+)-(7S,8R)-7-Hydroxy-7-methyl-1,4-dioxaspiro[4.5]decan-8-yl dodecanoate |
| (XIV)101438-57-b | 1916469-82-3 | (+)-(7S,8R)-7-Methyl-1,4-dioxaspiro[4.5]decane-7,8-diol |
| (XV)101438-57-b | 1916469-83-4 | (7S)-7-Hydroxy-7-methyl-1,4-dioxaspiro[4.5]decan-8-one |
| (XVI)101438-57-b | 1916469-84-5 | (7S,8S)-7-Methyl-1,4-dioxaspiro[4.5]decane-7,8-diol |
| (XVII)101438-57-b | 1916469-85-6 | (7S,8S)-8-(Benzyloxy)-7-methyl-1,4-dioxaspiro[4.5]decan-7-ol |
OptimisedRoute 80Steps 5 · Total yield /
(I)101438-58-a32981-86-5(II)101438-58-a108-24-7(III)101438-58-a27548-93-2(IV)101438-58-a115437-21-3(V)101438-58-a2061919-57-9(VI)101438-58-a2061919-58-0(VII)101438-58-a2061919-59-1(VIII)101438-58-a,(VIII)101438-58-b—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-58-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-58-a | 108-24-7 | Acetic acid acetic anhydride |
| (III)101438-58-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-58-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (V)101438-58-a | 2061919-57-9 | (2R,4S,5R)-2-(4-Methoxyphenyl)-4-phenyl-3-[(prop-2-en-1-yloxy)carbonyl]-1,3-oxazolidine-5-carboxylic acid |
| (VI)101438-58-a | 2061919-58-0 | 5-[(2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-13-yl] 3-prop-2-en-1-yl (2R,4S,5R)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (VII)101438-58-a | 2061919-59-1 | 5-[(2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-2-(benzoyloxy)-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-13-yl] 3-prop-2-en-1-yl (2R,4S,5R)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (VIII)101438-58-a,(VIII)101438-58-b | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-2-(benzoyloxy)-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-13-yl (2R,4S,5R)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate |
OptimisedRoute 81Steps 2 · Total yield /
(IX)101438-58-b133524-70-6(VIII)101438-58-a,(VIII)101438-58-b—(X)101438-58-b98-88-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (IX)101438-58-b | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (VIII)101438-58-a,(VIII)101438-58-b | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-2-(benzoyloxy)-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-13-yl (2R,4S,5R)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-5-carboxylate |
| (X)101438-58-b | 98-88-4 | alpha-Chlorobenzaldehyde |
OptimisedRoute 82Steps 13 · Total yield /
(I)101438-60-a33878-99-8(II)101438-60-a4242-00-6(III)101438-60-a1373344-35-4(IV)101438-60-a1373344-38-7(IX)101438-60-a—(V)101438-60-a2044680-25-1(VI)101438-60-a1373344-48-9(VII)101438-60-a1373344-41-2(VIII)101438-60-a39085-59-1(X)101438-60-a1612868-75-3(XI)101438-60-a2044680-29-5(XII)101438-60-a2044680-31-9(XIII)101438-60-a—(XIV)101438-60-a2044680-37-5(XV)101438-60-a2044680-41-1(XVI)101438-60-a,(XVI)101438-60-b2044680-52-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-60-a | 33878-99-8 | (S)-(+)-3,4,8,8a-Tetrahydro-8a-methyl-1,6(2H,7H)-naphthalenedione |
| (II)101438-60-a | 4242-00-6 | (4aS,5S)-5-Hydroxy-4a-methyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one |
| (III)101438-60-a | 1373344-35-4 | (4aS,5S)-4a-Methyl-5-[(triethylsilyl)oxy]-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one |
| (IV)101438-60-a | 1373344-38-7 | 3-[(1R,6S)-1-Methyl-2-oxo-6-[(triethylsilyl)oxy]cyclohexyl]propanoic acid |
| (IX)101438-60-a | - | N'-[(2S,4aS,8aS)-2-Methoxy-4a-methyloctahydro-5H-1-benzopyran-5-ylidene]-2,4,6-tri(propan-2-yl)benzene-1-sulfonohydrazide |
| (V)101438-60-a | 2044680-25-1 | S-Ethyl 3-[(1R,6S)-1-methyl-2-oxo-6-[(triethylsilyl)oxy]cyclohexyl]propanethioate |
| (VI)101438-60-a | 1373344-48-9 | (2S,4aR,8aS)-2-Hydroxy-4a-methyloctahydro-5H-1-benzopyran-5-one |
| (VII)101438-60-a | 1373344-41-2 | (2S,4aR,8aS)-2-Methoxy-4a-methyloctahydro-5H-1-benzopyran-5-one |
| (VIII)101438-60-a | 39085-59-1 | 2,4,6-Triisopropylbenzenesulfonohydrazide |
| (X)101438-60-a | 1612868-75-3 | 5-Methyl-2-(2-methylpent-3-yn-2-yl)-2-[(trimethylsilyl)oxy]hex-4-enal |
| (XI)101438-60-a | 2044680-29-5 | (1S,2S)-1-[(2S,4aS,8aS)-2-Methoxy-4a-methyl-3,4,4a,7,8,8a-hexahydro-2H-1-benzopyran-5-yl]-5-methyl-2-(2-methylpent-3-yn-2-yl)hex-4-ene-1,2-diol |
| (XII)101438-60-a | 2044680-31-9 | (4S,5S)-5-[(2S,4aS,8aS)-2-Methoxy-4a-methyl-3,4,4a,7,8,8a-hexahydro-2H-1-benzopyran-5-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
| (XIII)101438-60-a | - | (4S,5S)-5-[(4aS,8aS)-2-Hydroxy-4a-methyl-3,4,4a,7,8,8a-hexahydro-2H-1-benzopyran-5-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
| (XIV)101438-60-a | 2044680-37-5 | (4S,5S)-5-[(5S,6S)-5-Hydroxy-6-(3-hydroxypropyl)-6-methylcyclohex-1-en-1-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
| (XV)101438-60-a | 2044680-41-1 | (4S,5S)-5-[(5S,6S)-5-Hydroxy-6-methyl-6-(prop-2-en-1-yl)cyclohex-1-en-1-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
| (XVI)101438-60-a,(XVI)101438-60-b | 2044680-52-4 | (4S,5S)-5-[(5S,6S)-5-[(Benzyloxy)methoxy]-6-methyl-6-(prop-2-en-1-yl)cyclohex-1-en-1-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
OptimisedRoute 83Steps 4 · Total yield /
(XIX)101438-60-b—(XVI)101438-60-a,(XVI)101438-60-b2044680-52-4(XVII)101438-60-b—(XVIII)101438-60-b2044680-91-1(XX)101438-60-b2044680-93-3(XXI)101438-60-b2044680-94-4(XXII)101438-60-b2044680-95-5API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIX)101438-60-b | - | Lithiumbenzene |
| (XVI)101438-60-a,(XVI)101438-60-b | 2044680-52-4 | (4S,5S)-5-[(5S,6S)-5-[(Benzyloxy)methoxy]-6-methyl-6-(prop-2-en-1-yl)cyclohex-1-en-1-yl]-4-(3-methylbut-2-en-1-yl)-4-(2-methylpent-3-yn-2-yl)-1,3-dioxolan-2-one |
| (XVII)101438-60-b | - | (3aS,7Z,9aS,10S,13bS)-10-[(Benzyloxy)methoxy]-6,9a,14,14-tetramethyl-9,9a,10,11,12,13b-hexahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XVIII)101438-60-b | 2044680-91-1 | (1aR,1bS,2aS,3aS,6aS,10S,10aS,11aS)-10-[(Benzyloxy)methoxy]-1b,10a,12,12-tetramethyl-2a,3,8,9,10,10a,11,11a-octahydro-1bH,5H,6aH-1a,3a-methanobenzo[3,4]bisoxireno[6,7:8,9]cyclodeca[1,2-d][1,3]dioxol-5-one |
| (XX)101438-60-b | 2044680-93-3 | (1aR,2S,3S,5S,6S,10S,10aS,11aS)-10-[(Benzyloxy)methoxy]-5-hydroxy-2,10a,12,12-tetramethyl-3,4,5,6,8,9,10,10a,11,11a-decahydro-2H-2,3-epoxy-1a,5-methanobenzo[4,5]cyclodeca[1,2-b]oxiren-6-yl benzoate |
| (XXI)101438-60-b | 2044680-94-4 | (1S,5S,6S,8S,11S,12aS)-1-[(Benzyloxy)methoxy]-6,8,11-trihydroxy-9,12a,13,13-tetramethyl-1,2,3,5,6,7,8,11,12,12a-decahydro-6,10-methanobenzo[10]annulen-5-yl benzoate |
| (XXII)101438-60-b | 2044680-95-5 | (1S,5S,6S,8S,11S,12aS)-1-[(Benzyloxy)methoxy]-6,8-dihydroxy-9,12a,13,13-tetramethyl-11-[(triethylsilyl)oxy]-1,2,3,5,6,7,8,11,12,12a-decahydro-6,10-methanobenzo[10]annulen-5-yl benzoate |
OptimisedRoute 84Steps 4 · Total yield /
(I)101438-61-a10592-27-5(II)101438-61-a19810-31-2(III)101438-61-a2170896-25-8(IV)101438-61-a—(V)101438-61-a2170896-09-8API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-61-a | 10592-27-5 | 2,3-Dihydro-1H-pyrrolo[2,3-b]pyridine |
| (II)101438-61-a | 19810-31-2 | 2-(Benzyloxy)acetyl chloride |
| (III)101438-61-a | 2170896-25-8 | 2-(Benzyloxy)-1-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)ethan-1-one |
| (IV)101438-61-a | - | N-[(1Z)-Phenylmethylidene]benzamide |
| (V)101438-61-a | 2170896-09-8 | N-[(1S,2R)-2-(Benzyloxy)-3-(2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-1-yl)-3-oxo-1-phenylpropyl]benzamide |
OptimisedRoute 85Steps 10 · Total yield /
(I)101438-62-a563-96-2(II)101438-62-a1576-35-8(III)101438-62-a956748-54-2(IV)101438-62-a2097366-34-0(IX)101438-62-a100-52-7(V)101438-62-a6066-82-6(VI)101438-62-a147666-20-4(VII)101438-62-a109-73-9(VIII)101438-62-a357262-31-8(X)101438-62-a2292240-12-9(XI)101438-62-a2292240-41-4(XII)101438-62-a126060-73-9(XIII)101438-62-a144787-20-2(XIV)101438-62-a98-88-4(XV)101438-62-a246861-68-7(XVI)101438-62-a153433-80-8API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-62-a | 563-96-2 | Dihydroxyacetic acid |
| (II)101438-62-a | 1576-35-8 | 4-Methylbenzenesulfonhydrazide |
| (III)101438-62-a | 956748-54-2 | (2E)-[2-(4-Methylbenzene-1-sulfonyl)hydrazinylidene]acetic acid |
| (IV)101438-62-a | 2097366-34-0 | (2E)-[2-(4-Methylbenzene-1-sulfonyl)hydrazinylidene]acetyl chloride |
| (IX)101438-62-a | 100-52-7Available | Benzaldehyde |
| (V)101438-62-a | 6066-82-6 | 1-Hydroxy-2,5-pyrrolidinedione |
| (VI)101438-62-a | 147666-20-4 | 2,5-Dioxopyrrolidin-1-yl 2-diazoacetate |
| (VII)101438-62-a | 109-73-9 | 1-Aminobutane |
| (VIII)101438-62-a | 357262-31-8 | N-Butyl-2-diazoacetamide |
| (X)101438-62-a | 2292240-12-9 | (2R,3R)-N-Butyl-3-phenyloxirane-2-carboxamide |
| (XI)101438-62-a | 2292240-41-4 | tert-Butyl butyl[(2R,3R)-3-phenyloxirane-2-carbonyl]carbamate |
| (XII)101438-62-a | 126060-73-9 | Ethyl (2R,3R)-3-phenyloxirane-2-carboxylate |
| (XIII)101438-62-a | 144787-20-2 | Ethyl (2R,3S)-3-azido-2-hydroxy-3-phenylpropanoate |
| (XIV)101438-62-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (XV)101438-62-a | 246861-68-7 | (1S,2R)-1-Azido-3-ethoxy-3-oxo-1-phenylpropan-2-yl benzoate |
| (XVI)101438-62-a | 153433-80-8 | Ethyl (2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoate |
OptimisedRoute 86Steps 4 · Total yield /
(I)101438-63-a71610-00-9(II)101438-63-a133524-70-6(III)101438-63-a2402698-73-9(IV)101438-63-a65-85-0(V)101438-63-a181375-43-9API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-63-a | 71610-00-9 | Benzoic acid (2alpha,5beta,7beta,10beta,13alpha)-4,10-diacetoxy-1,7-dihydroxy-13-[2(R)-hydroxy-3(S)-[2-methyl-2(E)-butenoylamino]-3-phenylpropionyloxy]-9-oxo-5,20-epoxytax-11-en-2-yl ester |
| (II)101438-63-a | 133524-70-6 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-63-a | 2402698-73-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-([(2R,3S)-3-amino-3-phenyl-2-[(trimethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-9-oxo-7-[(trimethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-63-a | 65-85-0 | Benzenecarboxylic acid |
| (V)101438-63-a | 181375-43-9 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-([(2R,3S)-3-benzamido-3-phenyl-2-[(trimethylsilyl)oxy]propanoyl]oxy)-1-hydroxy-9-oxo-7-[(trimethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoat e |
OptimisedRoute 87Steps 5 · Total yield /
(I)101438-64-a27548-93-2(II)101438-64-a32981-89-8(III)101438-64-a150665-56-8(IV)101438-64-a—(V)101438-64-a149249-91-2(VI)101438-64-a—(VII)101438-64-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-64-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-64-a | 32981-89-8 | (1S,2S,3R,4S,7R,9S,10S,12R)-4,12-bis(acetyloxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11,15-dioxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (III)101438-64-a | 150665-56-8 | (1S,2S,3R,4S,7R,9S,10S,12R)-4,12-bis(acetyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11,15-dioxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IV)101438-64-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-hydrogenio-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (V)101438-64-a | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (VI)101438-64-a | - | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-hydrogenio-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-{[(2R,3S)-3-phenyl-3-(phenylformamido)-2-[(triethylsilyl)oxy]propanoyl]oxy}-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (VII)101438-64-a | - | (2alpha,5beta,7beta,10beta,13beta)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy]-1,7-dihydroxy-9-oxo-13-tritio-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 88Steps 6 · Total yield /
(I)101438-66-a1384288-59-8(II)101438-66-a545-06-2(III)101438-66-a2642356-03-2(IV)101438-66-a2642356-02-1(IX)101438-66-a132201-33-3(V)101438-66-a2642356-05-4(VI)101438-66-a1454840-57-3(VII)101438-66-a98-88-4(VIII)101438-66-a103150-32-9(X)101438-66-a136561-53-0(XI)101438-66-a145514-62-1API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-66-a | 1384288-59-8 | (1S,2S)-3-[[tert-Butyl(dimethyl)silyl]oxy]-1-phenylpropane-1,2-diol |
| (II)101438-66-a | 545-06-2 | 2,2,2-Trichloroacetonitrile |
| (III)101438-66-a | 2642356-03-2 | (1S,2S)-3-[[tert-Butyl(dimethyl)silyl]oxy]-1-phenylpropane-1,2-diyl bis(2,2,2-trichloroethanimidate) |
| (IV)101438-66-a | 2642356-02-1 | (4S,5R)-5-([[tert-Butyl(dimethyl)silyl]oxy]methyl)-4-phenyl-2-(trichloromethyl)-4,5-dihydro-1,3-oxazole |
| (IX)101438-66-a | 132201-33-3 | (2R,3S)-2-Hydroxy-3-phenyl-3-(phenylformamido)propanoic acid |
| (V)101438-66-a | 2642356-05-4 | N-((1S,2R)-3-TBDMSoxy-2-hydroxy-1-phenylpropyl)-2,2,2-trichloroacetamide |
| (VI)101438-66-a | 1454840-57-3 | (2R,3S)-3-Amino-3-phenylpropane-1,2-diol |
| (VII)101438-66-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (VIII)101438-66-a | 103150-32-9 | N-[(1S,2R)-2,3-Dihydroxy-1-phenylpropyl]benzamide |
| (X)101438-66-a | 136561-53-0 | (2R,3S)-3-Amino-2-hydroxy-3-phenylpropanoic acid |
| (XI)101438-66-a | 145514-62-1 | (2R,3S)-3-[(tert-Butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoic acid |
OptimisedRoute 89Steps 8 · Total yield /
(I)101438-67-a107-86-8(II)101438-67-a31058-93-2(III)101438-67-a2344-80-1(IV)101438-67-a2416730-68-0(IX)101438-67-a—(V)101438-67-a37710-51-3(VI)101438-67-a1193-18-6(VII)101438-67-a—(VIII)101438-67-a1826-67-1(X)101438-67-a,(X)101438-67-b126726-62-3(XI)101438-67-a—(XII)101438-67-a—(XIII)101438-67-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-67-a | 107-86-8 | 3-Methyl-2-butenal |
| (II)101438-67-a | 31058-93-2 | 2-Bromo-3-methylbut-2-enal |
| (III)101438-67-a | 2344-80-1 | (Trimethylsilyl)methyl chloride |
| (IV)101438-67-a | 2416730-68-0 | 3-Bromo-4-methyl-1-(trimethylsilyl)pent-3-en-2-ol |
| (IX)101438-67-a | - | 1-[6-(3-Bromo-4-methylpent-3-en-1-yl)-2-chlorocyclohex-1-en-1-yl]prop-2-en-1-ol |
| (V)101438-67-a | 37710-51-3 | 3-Bromo-4-methylpenta-1,3-diene |
| (VI)101438-67-a | 1193-18-6 | 3-Methyl-2-cyclohexen-1-one |
| (VII)101438-67-a | - | 6-(3-Bromo-4-methylpent-3-en-1-yl)-2-chlorocyclohex-1-ene-1-carbaldehyde |
| (VIII)101438-67-a | 1826-67-1Available | (Vinyl)magnesium bromide |
| (X)101438-67-a,(X)101438-67-b | 126726-62-3 | 2-Isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane |
| (XI)101438-67-a | - | 1-[2-Chloro-6-[4-methyl-3-(prop-1-en-2-yl)pent-3-en-1-yl]cyclohex-1-en-1-yl]prop-2-en-1-ol |
| (XII)101438-67-a | - | 1-[2-Chloro-6-[4-methyl-3-(prop-1-en-2-yl)pent-3-en-1-yl]cyclohex-1-en-1-yl]prop-2-en-1-one |
| (XIII)101438-67-a | - | (12aS)-4-Chloro-9,12a,13,13-tetramethyl-2,3,6,7,8,11,12,12a-octahydro-6,10-methanobenzo[10]annulen-5(1H)-one |
OptimisedRoute 90Steps 3 · Total yield /
(X)101438-67-a,(X)101438-67-b126726-62-3(XIV)101438-67-b67-64-1(XV)101438-67-b—(XVI)101438-67-b676593-24-1(XVII)101438-67-b—(XVIII)101438-67-b881172-81-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (X)101438-67-a,(X)101438-67-b | 126726-62-3 | 2-Isopropenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane |
| (XIV)101438-67-b | 67-64-1Available | 2-Propanal |
| (XV)101438-67-b | - | 2,2'-(Propane-2,2-diyl)bis(5,5-dimethyl-1,3,2-dioxaborinane) |
| (XVI)101438-67-b | 676593-24-1 | 5,5-Dimethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborinane |
| (XVII)101438-67-b | - | 2,2'-(Propane-2,2-diyl)bis(2H-1,3,2-benzodioxaborole) |
| (XVIII)101438-67-b | 881172-81-2 | 2-(Prop-1-en-2-yl)-2H-1,3,2-benzodioxaborole |
OptimisedRoute 91Steps 10 · Total yield /
(XVIII)101438-68-a2413947-55-2(XVII)101438-68-a2413947-54-1(XIX)101438-68-a2413947-56-3(XVI)101438-68-a2413947-52-9(III)101438-68-a22715-57-7(XIV)101438-68-a1350704-14-1(VII)101438-68-a1826-67-1(I)101438-68-a—(XV)101438-68-a3739-30-8(X)101438-68-a107-02-8(VIII)101438-68-a1350704-10-7(IV)101438-68-a4773-87-9(V)101438-68-a40996-91-6(VI)101438-68-a5323-87-5(XII)101438-68-a75-24-1(IX)101438-68-a75-16-1(II)101438-68-a75-25-2(XIII)101438-68-a1350704-15-2(XX)101438-68-a,(XX)101438-68-b2413947-57-4(XIa)101438-68-a—(XIb)101438-68-a1350704-13-0API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XVIII)101438-68-a | 2413947-55-2 | (3S,4aR,6R,11S,12aS)-3-Bromo-9,12a,13,13-tetramethyl-11-[(triethylsilyl)oxy]-2,3,4a,6,7,11,12,12a-octahydro-6,10-methanobenzo[10]annulene-4,5,8(1H)-trione |
| (XVII)101438-68-a | 2413947-54-1 | (3S,4aR,6R,12aR)-3-Bromo-9,12a,13,13-tetramethyl-2,3,4a,6,7,11,12,12a-octahydro-6,10-methanobenzo[10]annulene-4,5,8(1H)-trione |
| (XIX)101438-68-a | 2413947-56-3 | (4aS,6R,11S,12aS)-9,12a,13,13-Tetramethyl-11-[(triethylsilyl)oxy]-4a,6,7,11,12,12a-hexahydro-6,10-methanobenzo[10]annulene-4,5,8(1H)-trione |
| (XVI)101438-68-a | 2413947-52-9 | (4aS,6R,12aS)-9,12a,13,13-Tetramethyl-2,3,4a,6,7,11,12,12a-octahydro-6,10-methanobenzo[10]annulene-4,5,8(1H)-trione |
| (III)101438-68-a | 22715-57-7 | 1,1-Dibromo-2,2,3,3-tetramethylcyclopropane |
| (XIV)101438-68-a | 1350704-14-1 | (4aS,6R,12aS)-9,12a,13,13-Tetramethyl-2,3,6,7,8,11,12,12a-octahydro-6,10-methanobenzo[10]annulene-4,5(1H,4aH)-dione |
| (VII)101438-68-a | 1826-67-1Available | (Vinyl)magnesium bromide |
| (I)101438-68-a | - | 1,1,2,2-Tetramethylethylene |
| (XV)101438-68-a | 3739-30-8 | 2-Hydroxy-2-methylbutanoic acid |
| (X)101438-68-a | 107-02-8 | 2-Propen-1-one |
| (VIII)101438-68-a | 1350704-10-7 | 3-(3-Isopropenyl-4-methyl-3-pentenyl)-2-cyclohexen-1-one |
| (IV)101438-68-a | 4773-87-9 | 3-Bromo-2,4-dimethylpenta-1,3-diene |
| (V)101438-68-a | 40996-91-6 | 3-Ethenylcyclohex-2-en-1-one |
| (VI)101438-68-a | 5323-87-5 | 3-Ethoxy-2-cyclohexen-1-one |
| (XII)101438-68-a | 75-24-1 | Aluminum trimethanide |
| (IX)101438-68-a | 75-16-1Available | Methylmagnesium bromide |
| (II)101438-68-a | 75-25-2 | Bromoform |
| (XIII)101438-68-a | 1350704-15-2 | Trimethyl([(3S)-3-methyl-3-[4-methyl-3-(prop-1-en-2-yl)pent-3-en-1-yl]cyclohex-1-en-1-yl]oxy)silane |
| (XX)101438-68-a,(XX)101438-68-b | 2413947-57-4 | (2beta,4alpha,10beta,13alpha)-10-[(Triethylsilyl)oxy](2-~2~H)taxa-5,11-diene-2,4,13-triol |
| (XIa)101438-68-a | - | (2S,3S)-2,3-Dimethyl-3-[4-methyl-3-(prop-1-en-2-yl)pent-3-en-1-yl]-2-(prop-2-enoyl)cyclohexan-1-one |
| (XIb)101438-68-a | 1350704-13-0 | (2S,3S)-3-Methyl-3-[4-methyl-3-(prop-1-en-2-yl)pent-3-en-1-yl]-2-(prop-2-enoyl)cyclohexan-1-one |
OptimisedRoute 92Steps 9 · Total yield /
(XXIII)101438-68-b2413947-62-1(XXIX)101438-68-b,(XXIX)101438-68-c—(XX)101438-68-a,(XX)101438-68-b2413947-57-4(XXI)101438-68-b—(XXII)101438-68-b2413947-59-6(XXVIII)101438-68-b—(XXVII)101438-68-b—(XXV)101438-68-b2413947-64-3(XXVI)101438-68-b2413947-65-4(XXIV)101438-68-b2413947-63-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXIII)101438-68-b | 2413947-62-1 | (4alpha,5alpha,6alpha,10beta,13alpha)-13-[[tert-Butyl(dimethyl)silyl]oxy]-1,4-dihydroxy-10-[(triethylsilyl)oxy]-5,6-epoxytax-11-en-2-one |
| (XXIX)101438-68-b,(XXIX)101438-68-c | - | (1S,5S,6R,7S,8S,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3-oxo-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-8-yl methanesulfonate |
| (XX)101438-68-a,(XX)101438-68-b | 2413947-57-4 | (2beta,4alpha,10beta,13alpha)-10-[(Triethylsilyl)oxy](2-~2~H)taxa-5,11-diene-2,4,13-triol |
| (XXI)101438-68-b | - | (2beta,4alpha,10beta,13alpha)-13-[[tert-Butyl(dimethyl)silyl]oxy]-10-[(triethylsilyl)oxy](2-~2~H)taxa-5,11-diene-1,2,4-triol |
| (XXII)101438-68-b | 2413947-59-6 | (2beta,4alpha,5alpha,6alpha,10beta,13alpha)-13-[[tert-Butyl(dimethyl)silyl]oxy]-10-[(triethylsilyl)oxy](2-~2~H)-5,6-epoxytax-11-ene-1,2,4-triol |
| (XXVIII)101438-68-b | - | (3aS,5S,8S,9aR,10S,12S,13aS,13bS)-10-[(Benzyloxy)methyl]-5-[[tert-butyl(dimethyl)silyl]oxy]-12-hydroxy-6,9a,14,14-tetramethyl-13-methylidene-8-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XXVII)101438-68-b | - | (3aS,5S,8S,9aR,10S,12S,13S,13aR,13bS)-10-[(Benzyloxy)methyl]-5-[[tert-butyl(dimethyl)silyl]oxy]-13-hydroxy-6,9a,13,14,14-pentamethyl-8-[(triethylsilyl)oxy]-12-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XXV)101438-68-b | 2413947-64-3 | (3aS,5S,8S,9aS,10R,11R,12S,13S,13aR,13bS)-5-[[tert-Butyl(dimethyl)silyl]oxy]-13-hydroxy-6,9a,13,15,15-pentamethyl-8-[(triethylsilyl)oxy]-12-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-10,11-epoxy-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XXVI)101438-68-b | 2413947-65-4 | (3aS,5S,8S,9aS,10S,12S,13S,13aR,13bS)-5-[[tert-Butyl(dimethyl)silyl]oxy]-10,13-dihydroxy-6,9a,13,14,14-pentamethyl-8-[(triethylsilyl)oxy]-12-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XXIV)101438-68-b | 2413947-63-2 | (3aS,5S,8S,9aS,11S,12S,13S,13aR,13bS)-5-[[tert-Butyl(dimethyl)silyl]oxy]-13-hydroxy-6,9a,13,15,15-pentamethyl-8-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-11,12-epoxy-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
OptimisedRoute 93Steps 6 · Total yield /
(XXIX)101438-68-b,(XXIX)101438-68-c—(XXX)101438-68-c—(XXXI)101438-68-c—(XXXII)101438-68-c—(XXXIII)101438-68-c—(XXXIV)101438-68-c—(XXXV)101438-68-c2413947-75-6(XXXVI)101438-68-c—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXIX)101438-68-b,(XXIX)101438-68-c | - | (1S,5S,6R,7S,8S,10S,11R,13R,16S)-10-[(benzyloxy)methyl]-16-[(tert-butyldimethylsilyl)oxy]-7-hydroxy-7-(hydroxymethyl)-11,15,18,18-tetramethyl-3-oxo-13-[(triethylsilyl)oxy]-2,4-dioxatetracyclo[12.3.1.0(1,5).0(6,11)]octadec-14-en-8-yl methanesulfonate |
| (XXX)101438-68-c | - | (3aS,5S,9aR,10S,11aR,13aS,13bR,13cS)-10-[(Benzyloxy)methyl]-5-[[tert-butyl(dimethyl)silyl]oxy]-13a-hydroxy-6,9a,14,14-tetramethyl-4,5,9a,10,11,11a,13,13a,13b,13c-decahydro-2H-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxete-2,8(9H)-dione |
| (XXXI)101438-68-c | - | (2alpha,5beta,7beta,10beta,13alpha)-7-[(Benzyloxy)methyl]-13-[[tert-butyl(dimethyl)silyl]oxy]-1,2,4,10-tetrahydroxy-5,20-epoxytax-11-en-9-one |
| (XXXII)101438-68-c | - | (3aS,5S,8R,9aR,10S,11aR,13aS,13bR,13cS)-10-[(Benzyloxy)methyl]-5-[[tert-butyl(dimethyl)silyl]oxy]-6,9a,14,14-tetramethyl-2,9-dioxo-4,5,8,9,9a,10,11,11a,13b,13c-decahydro-2H-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxete-8,13a(13H)-diyl diacetate |
| (XXXIII)101438-68-c | - | Lithiumbenzene |
| (XXXIV)101438-68-c | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-7-[(benzyloxy)methyl]-1,13-dihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XXXV)101438-68-c | 2413947-75-6 | (3R,4S)-1-Benzoyl-3-(benzyloxy)-4-phenylazetidin-2-one |
| (XXXVI)101438-68-c | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-benzamido-2-(benzyloxy)-3-phenylpropanoyl]oxy]-7-[(benzyloxy)methyl]-1-hydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 94Steps 6 · Total yield /
(I)101438-69-a104-55-2(II)101438-69-a257947-27-6(III)101438-69-a150949-07-8(IV)101438-69-a98-88-4(IX)101438-69-a—(V)101438-69-a144541-45-7(VI)101438-69-a32981-85-4(VII)101438-69-a2186-92-7(VIII)101438-69-a—(X)101438-69-a132201-32-2(XI)101438-69-a131968-74-6API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-69-a | 104-55-2 | Cinnamal |
| (II)101438-69-a | 257947-27-6 | (2S,3S)-3-Amino-2-hydroxy-3-phenylpropanamide |
| (III)101438-69-a | 150949-07-8 | Methyl (2S,3S)-3-amino-2-hydroxy-3-phenylpropanoate |
| (IV)101438-69-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (IX)101438-69-a | - | (4S,5R)-3-Benzoyl-2-[(4-methoxyphenyl)methyl]-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (V)101438-69-a | 144541-45-7 | Methyl (2S,3S)-3-benzamido-2-hydroxy-3-phenylpropanoate |
| (VI)101438-69-a | 32981-85-4 | Methyl (2R,3S)-2-hydroxy-3-phenyl-3-(phenylformamido)propanoate |
| (VII)101438-69-a | 2186-92-7 | 1-(Dimethoxymethyl)-4-methoxybenzene |
| (VIII)101438-69-a | - | Methyl (4S,5R)-3-benzoyl-2-[(4-methoxyphenyl)methyl]-4-phenyl-1,3-oxazolidine-5-carboxylate |
| (X)101438-69-a | 132201-32-2 | (2R,3S)-3-Amino-2-hydroxy-3-phenylpropanoic acid hydrochloride |
| (XI)101438-69-a | 131968-74-6 | (2R,3S)-3-Phenylisoserine methyl ester |
OptimisedRoute 95Steps 8 · Total yield /
(I)101438-70-a100-52-7(II)101438-70-a104-94-9(III)101438-70-a783-08-4(IV)101438-70-a13831-31-7(IX)101438-70-a144465-78-1(V)101438-70-a186613-02-5(VI)101438-70-a194234-97-4(VII)101438-70-a94612-33-6(VIII)101438-70-a146924-94-9(X)101438-70-a132127-31-2(XI)101438-70-a98-88-4(XII)101438-70-a155371-59-8API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-70-a | 100-52-7Available | Benzaldehyde |
| (II)101438-70-a | 104-94-9 | 1-Amino-4-methoxybenzene |
| (III)101438-70-a | 783-08-4 | (NZ)-4-Methoxy-N-(phenylmethylidene)aniline |
| (IV)101438-70-a | 13831-31-7 | (2-Chloranyl-2-oxidanylideneethyl) ethanoate |
| (IX)101438-70-a | 144465-78-1 | (3R,4S)-1-(4-Methoxyphenyl)-4-phenyl-3-[[tri(propan-2-yl)silyl]oxy]azetidin-2-one |
| (V)101438-70-a | 186613-02-5 | 1-(4-Methoxyphenyl)-2-oxo-4-phenylazetidin-3-yl acetate |
| (VI)101438-70-a | 194234-97-4 | 3-Hydroxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one |
| (VII)101438-70-a | 94612-33-6 | 1-(4-Methoxyphenyl)-4-phenylazetidine-2,3-dione |
| (VIII)101438-70-a | 146924-94-9 | (+)-3-Hydroxy-1-(4-methoxyphenyl)-4-phenylazetidin-2-one |
| (X)101438-70-a | 132127-31-2 | (3R,4S)-4-Phenyl-3-{[tris(propan-2-yl)silyl]oxy}azetidin-2-one |
| (XI)101438-70-a | 98-88-4 | alpha-Chlorobenzaldehyde |
| (XII)101438-70-a | 155371-59-8 | (3R,4S)-1-Benzoyl-4-phenyl-3-[[tri(propan-2-yl)silyl]oxy]azetidin-2-one |
OptimisedRoute 96Steps 4 · Total yield /
(XIII)101438-70-b—(XIV)101438-70-b—(XV)101438-70-b75-16-1(XVI)101438-70-b—(XVII)101438-70-b528854-24-2(XVIII)101438-70-b—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIII)101438-70-b | - | (aS)-(-)-1,1'-Bi-2-naphthol |
| (XIV)101438-70-b | - | (aS)-[1,1'-Binaphthalene]-2,2'-diyl bis(trifluoromethanesulfonate) |
| (XV)101438-70-b | 75-16-1Available | Methylmagnesium bromide |
| (XVI)101438-70-b | - | (aS)-2,2'-Dimethyl-1,1'-binaphthalene |
| (XVII)101438-70-b | 528854-24-2 | (aS)-4-tert-Butyl-4,5-dihydro-3H-4lambda5-dinaphtho[2,1-c:1',2'-e]phosphepine-4-thione |
| (XVIII)101438-70-b | - | (aS)-(4R,4'R)-4,4'-Di-tert-butyl-4,4',5,5'-tetrahydro-3H,3'H-[3,3'-bi-4lambda5-dinaphtho[2,1-c:1',2'-e]phosphepine]-4,4'-dithione |
OptimisedRoute 97Steps 11 · Total yield /
(I)101438-71-a90130-91-9(II)101438-71-a2730017-90-8(III)101438-71-a2730017-91-9(IV)101438-71-a2730017-92-0(IX)101438-71-a2730017-96-4(V)101438-71-a2730017-93-1(VI)101438-71-a2730017-94-2(VII)101438-71-a2730017-95-3(VIII)101438-71-a173073-81-9(X)101438-71-a2730017-97-5(XI)101438-71-a2730017-98-6(XII)101438-71-a2730017-99-7(XIII)101438-71-a,(XIII)101438-71-b2730018-00-3API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-71-a | 90130-91-9 | (2R,3S)-3-Hydroxy-2-methyl-2-(prop-2-en-1-yl)cyclohexan-1-one |
| (II)101438-71-a | 2730017-90-8 | (2R,3S)-3-(Benzyloxy)-2-methyl-2-(prop-2-en-1-yl)cyclohexan-1-one |
| (III)101438-71-a | 2730017-91-9 | [(3R,4S)-4-(Benzyloxy)-2-bromo-3-methyl-3-(prop-2-en-1-yl)cyclohex-1-en-1-yl]methanol |
| (IV)101438-71-a | 2730017-92-0 | ([[(1S,2R)-3-Bromo-2,4-dimethyl-2-(prop-2-en-1-yl)cyclohex-3-en-1-yl]oxy]methyl)benzene |
| (IX)101438-71-a | 2730017-96-4 | (4S,5S)-4-[(1S,6S)-6-(Benzyloxy)-2-bromo-1,3-dimethylcyclohex-2-en-1-yl]-2,2-dimethyl-5-(6,6,8-trimethyl-1,4-dithiaspiro[4.5]dec-7-en-7-yl)-1,3-dioxolane |
| (V)101438-71-a | 2730017-93-1 | [(1R,6S)-6-(Benzyloxy)-2-bromo-1,3-dimethylcyclohex-2-en-1-yl]acetaldehyde |
| (VI)101438-71-a | 2730017-94-2 | ([2-[(1R,6S)-6-(Benzyloxy)-2-bromo-1,3-dimethylcyclohex-2-en-1-yl]ethenyl]oxy)(tert-butyl)dimethylsilane |
| (VII)101438-71-a | 2730017-95-3 | (2S)-[(1S,6S)-6-(Benzyloxy)-2-bromo-1,3-dimethylcyclohex-2-en-1-yl][(2-methoxypropan-2-yl)oxy]acetaldehyde |
| (VIII)101438-71-a | 173073-81-9 | 7-Iodo-6,6,8-trimethyl-1,4-dithiaspiro[4.5]dec-7-ene |
| (X)101438-71-a | 2730017-97-5 | (5S,6S)-5-(Benzyloxy)-6-[(4S,5S)-2,2-dimethyl-5-(6,6,8-trimethyl-1,4-dithiaspiro[4.5]dec-7-en-7-yl)-1,3-dioxolan-4-yl]-2,6-dimethylcyclohex-1-ene-1-carbaldehyde |
| (XI)101438-71-a | 2730017-98-6 | (5S,6S)-5-(Benzyloxy)-6-[(4S,5S)-2,2-dimethyl-5-(2,6,6-trimethyl-5-oxocyclohex-1-en-1-yl)-1,3-dioxolan-4-yl]-2,6-dimethylcyclohex-1-ene-1-carbaldehyde |
| (XII)101438-71-a | 2730017-99-7 | (3aS,8S,9S,13S,13aS,13bS)-13-(Benzyloxy)-2,2,5,10,13a,14,14-heptamethyl-6,7,9,11,12,13,13a,13b-octahydro-2H-4,8-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-8,9(3aH)-diol |
| (XIII)101438-71-a,(XIII)101438-71-b | 2730018-00-3 | (1S,5S,10S,11S,12S,16S)-10-(Benzyloxy)-7,11,14,14,18,21,21-heptamethyl-2,4,13,15-tetraoxapentacyclo[15.3.1.0(1,5).0(6,11).0(12,16)]henicosa-6,17-dien-3-one |
OptimisedRoute 98Steps 7 · Total yield /
(XIII)101438-71-a,(XIII)101438-71-b2730018-00-3(XXI)101438-71-b—(XXII)101438-71-b,(XXII)101438-71-c—(XVII)101438-71-b2730018-04-7(XIX)101438-71-b2730018-10-5(XVIII)101438-71-b2730018-05-8(XIV)101438-71-b2730018-02-5(XVI)101438-71-b2730018-03-6(XX)101438-71-b1576-35-8(XV)101438-71-b,(XV)101438-71-c108-24-7API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIII)101438-71-a,(XIII)101438-71-b | 2730018-00-3 | (1S,5S,10S,11S,12S,16S)-10-(Benzyloxy)-7,11,14,14,18,21,21-heptamethyl-2,4,13,15-tetraoxapentacyclo[15.3.1.0(1,5).0(6,11).0(12,16)]henicosa-6,17-dien-3-one |
| (XXI)101438-71-b | - | (3aS,5S,8R,9aS,10S,13bS)-5-Hydroxy-6,9a,13,14,14-pentamethyl-12-[2-(4-methylbenzene-1-sulfonyl)hydrazinylidene]-2,9-dioxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XXII)101438-71-b,(XXII)101438-71-c | - | (3aS,5S,8R,9aS,10S,13bS)-6,9a,13,14,14-Pentamethyl-12-[2-(4-methylbenzene-1-sulfonyl)hydrazinylidene]-2,9-dioxo-10-[(triethylsilyl)oxy]-5-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XVII)101438-71-b | 2730018-04-7 | (3aS,8R,9aS,10S,13bS)-10-(Benzyloxy)-6,9a,13,14,14-pentamethyl-2,9-dioxo-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XIX)101438-71-b | 2730018-10-5 | (3aS,8R,9aS,10S,13bS)-6,9a,13,14,14-Pentamethyl-2,5,9,12-tetraoxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XVIII)101438-71-b | 2730018-05-8 | (3aS,8R,9aS,10S,13bS)-6,9a,13,14,14-Pentamethyl-2,9-dioxo-10-[(triethylsilyl)oxy]-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XIV)101438-71-b | 2730018-02-5 | (3aS,8S,9S,9aR,10S,13bS)-10-(Benzyloxy)-8,9-dihydroxy-6,9a,13,14,14-pentamethyl-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (XVI)101438-71-b | 2730018-03-6 | (3aS,8S,9S,9aR,10S,13bS)-10-(Benzyloxy)-9-hydroxy-6,9a,13,14,14-pentamethyl-2-oxo-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XX)101438-71-b | 1576-35-8 | 4-Methylbenzenesulfonhydrazide |
| (XV)101438-71-b,(XV)101438-71-c | 108-24-7 | Acetic acid acetic anhydride |
OptimisedRoute 99Steps 7 · Total yield /
(XV)101438-71-b,(XV)101438-71-c108-24-7(XXII)101438-71-b,(XXII)101438-71-c—(XXIII)101438-71-c2730018-13-8(XXIV)101438-71-c2730018-14-9(XXIX)101438-71-c149249-91-2(XXV)101438-71-c2730018-16-1(XXVI)101438-71-c2730018-15-0(XXVII)101438-71-c—(XXVIII)101438-71-c—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XV)101438-71-b,(XV)101438-71-c | 108-24-7 | Acetic acid acetic anhydride |
| (XXII)101438-71-b,(XXII)101438-71-c | - | (3aS,5S,8R,9aS,10S,13bS)-6,9a,13,14,14-Pentamethyl-12-[2-(4-methylbenzene-1-sulfonyl)hydrazinylidene]-2,9-dioxo-10-[(triethylsilyl)oxy]-5-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XXIII)101438-71-c | 2730018-13-8 | (3aS,5S,8R,9aS,10S,13aR,13bS)-6,9a,13,14,14-Pentamethyl-2,9-dioxo-10-[(triethylsilyl)oxy]-5-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,13a,13b-octahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XXIV)101438-71-c | 2730018-14-9 | (3aS,5S,8R,9aS,10S,12S,13aR,13bS)-12-Hydroxy-6,9a,14,14-tetramethyl-13-methylidene-2,9-dioxo-10-[(triethylsilyl)oxy]-5-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XXIX)101438-71-c | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (XXV)101438-71-c | 2730018-16-1 | (3aS,5S,8R,9aS,10S,12S,13aR,13bS)-12-[(Methanesulfonyl)oxy]-6,9a,14,14-tetramethyl-13-methylidene-2,9-dioxo-10-[(triethylsilyl)oxy]-5-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XXVI)101438-71-c | 2730018-15-0 | (3aS,5S,8R,9aS,10S,12S,13S,13aR,13bS)-13-Hydroxy-13-(hydroxymethyl)-12-[(methanesulfonyl)oxy]-6,9a,14,14-tetramethyl-2,9-dioxo-10-[(triethylsilyl)oxy]-5-[(trimethylsilyl)oxy]-5,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-8-yl acetate |
| (XXVII)101438-71-c | - | (3aS,5S,8R,9aS,10S,11aR,13aS,13bR,13cS)-5-Hydroxy-6,9a,14,14-tetramethyl-2,9-dioxo-10-[(triethylsilyl)oxy]-4,5,8,9,9a,10,11,11a,13b,13c-decahydro-2H-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxete-8,13a(13H)-diyl diacetate |
| (XXVIII)101438-71-c | - | Dilithium (3aS,5S,8R,9aS,10S,11aR,13aS,13bR,13cS)-8,13a-bis(acetyloxy)-6,9a,14,14-tetramethyl-9-oxo-2-phenyl-10-[(triethylsilyl)oxy]-4,5,8,9,9a,10,11,11a,13,13a,13b,13c-dodecahydro-2H-3a,7-methano[1,3]dioxolo[9,10]cyclodeca[1,2-d][1]benzoxete-2,5-bis(olate) |
OptimisedRoute 100Steps 11 · Total yield /
(I)101438-72-a—(II)101438-72-a—(III)101438-72-a—(IV)101438-72-a—(IX)101438-72-a2757103-66-3(V)101438-72-a—(VI)101438-72-a—(VII)101438-72-a—(VIII)101438-72-a2757103-54-9(X)101438-72-a2757103-55-0(XI)101438-72-a2757103-56-1(XII)101438-72-a—(XIII)101438-72-a,(XIII)101438-72-b2757103-57-2API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-72-a | - | (3aS,7S,9aS,10S,13S,13aS,13bS)-8-Hydroxy-13-(methoxymethoxy)-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (II)101438-72-a | - | (3aS,7S,9aS,10S,13S,13aS,13bS)-8,13-Dihydroxy-6,9a,14,14-tetramethyl-2-oxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (III)101438-72-a | - | (3aS,7S,9aS,10S,13aR,13bS)-6,9a,14,14-Tetramethyl-2,8,13-trioxo-7,8,9,9a,10,11,12,13,13a,13b-decahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-10-yl benzoate |
| (IV)101438-72-a | - | (3aS,7S,9aS,10S,13aR,13bS)-10-Hydroxy-6,9a,14,14-tetramethyl-9a,10,11,12,13a,13b-hexahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8,13(7H,9H)-trione |
| (IX)101438-72-a | 2757103-66-3 | (3aS,5S,9aS,10S,12R,13aR,13bS)-6,9a,14,14-Tetramethyl-5,10,12-tris[(triethylsilyl)oxy]-9a,10,11,12,13a,13b-hexahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8,13(5H,9H)-trione |
| (V)101438-72-a | - | (3aS,7S,9aS,10S,13aR,13bS)-6,9a,14,14-Tetramethyl-10-[(triethylsilyl)oxy]-9a,10,11,12,13a,13b-hexahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8,13(7H,9H)-trione |
| (VI)101438-72-a | - | (3aS,7E,9aS,10S,13aR,13bS)-6,9a,14,14-Tetramethyl-8,10,13-tris[(triethylsilyl)oxy]-9,9a,10,11,13a,13b-hexahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (VII)101438-72-a | - | (3aS,3bR,4R,5R,7S,7aS,9Z,10aR,11aS,12aS)-7a,10a,13,13-Tetramethyl-4,7,9-tris[(triethylsilyl)oxy]-3b,4,5,6,7,7a,8,10a,11a,12-decahydro-2H,3aH-4,5-epoxy-10,12a-methanobenzo[3,4]oxireno[8,9]cyclodeca[1,2-d][1,3]dioxol-2-one |
| (VIII)101438-72-a | 2757103-54-9 | (3aS,5S,9aS,10S,12R,13aR,13bS)-5,12-Dihydroxy-6,9a,14,14-tetramethyl-10-[(triethylsilyl)oxy]-9a,10,11,12,13a,13b-hexahydro-2H,4H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8,13(5H,9H)-trione |
| (X)101438-72-a | 2757103-55-0 | (3aS,5S,9aS,10S,12R,13S,13aR,13bS)-13-Hydroxy-6,9a,13,14,14-pentamethyl-5,10,12-tris[(triethylsilyl)oxy]-4,5,9,9a,10,11,12,13,13a,13b-decahydro-2H,8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8-dione |
| (XI)101438-72-a | 2757103-56-1 | (3aS,5S,9aS,10S,12R,13aR,13bS)-6,9a,14,14-Tetramethyl-13-methylidene-5,10,12-tris[(triethylsilyl)oxy]-4,5,9,9a,10,11,12,13,13a,13b-decahydro-2H,8H-3a,7-methanobenzo[3,4]cyclodeca[1,2-d][1,3]dioxole-2,8-dione |
| (XII)101438-72-a | - | Lithiumbenzene |
| (XIII)101438-72-a,(XIII)101438-72-b | 2757103-57-2 | (2alpha,5beta,7beta,13alpha)-1-Hydroxy-10-oxo-5,7,13-tris[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
OptimisedRoute 101Steps 5 · Total yield /
(XIII)101438-72-a,(XIII)101438-72-b2757103-57-2(XIV)101438-72-b—(XIX)101438-72-b,(XIX)101438-72-c2757103-60-7(XV)101438-72-b2757103-69-6(XVI)101438-72-b108-24-7(XVII)101438-72-b2757103-58-3(XVIII)101438-72-b2757103-59-4API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XIII)101438-72-a,(XIII)101438-72-b | 2757103-57-2 | (2alpha,5beta,7beta,13alpha)-1-Hydroxy-10-oxo-5,7,13-tris[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
| (XIV)101438-72-b | - | (2alpha,5beta,7beta,13alpha)-1-Hydroxy-9-methyl-10-oxo-5,7,13-tris[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
| (XIX)101438-72-b,(XIX)101438-72-c | 2757103-60-7 | (2alpha,5alpha,7beta,10beta,13alpha)-10-(Acetyloxy)-5-bromo-1-hydroxy-9-oxo-7,13-bis[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
| (XV)101438-72-b | 2757103-69-6 | (2alpha,5beta,7beta,10beta,13alpha)-1,10-Dihydroxy-9-oxo-5,7,13-tris[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
| (XVI)101438-72-b | 108-24-7 | Acetic acid acetic anhydride |
| (XVII)101438-72-b | 2757103-58-3 | (2alpha,5beta,7beta,10beta,13alpha)-10-(Acetyloxy)-1-hydroxy-9-oxo-5,7,13-tris[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
| (XVIII)101438-72-b | 2757103-59-4 | (2alpha,5beta,7beta,10beta,13alpha)-10-(Acetyloxy)-1,5-dihydroxy-9-oxo-7,13-bis[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
OptimisedRoute 102Steps 5 · Total yield /
(XXV)101438-72-c,(XXV)101438-72-d115437-21-3(XIX)101438-72-b,(XIX)101438-72-c2757103-60-7(XX)101438-72-c2757103-50-5(XXI)101438-72-c2757103-61-8(XXIII)101438-72-c150541-99-4(XXIV)101438-72-c27548-93-2(XXII)101438-72-c75-36-5API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXV)101438-72-c,(XXV)101438-72-d | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XIX)101438-72-b,(XIX)101438-72-c | 2757103-60-7 | (2alpha,5alpha,7beta,10beta,13alpha)-10-(Acetyloxy)-5-bromo-1-hydroxy-9-oxo-7,13-bis[(triethylsilyl)oxy]taxa-4(20),11-dien-2-yl benzoate |
| (XX)101438-72-c | 2757103-50-5 | (2alpha,5alpha,7beta,10beta,13alpha)-10-(Acetyloxy)-5-bromo-1,4,20-trihydroxy-9-oxo-7,13-bis[(triethylsilyl)oxy]tax-11-en-2-yl benzoate |
| (XXI)101438-72-c | 2757103-61-8 | (2alpha,5beta,7beta,10beta,13alpha)-10-(Acetyloxy)-1,4-dihydroxy-9-oxo-7,13-bis[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XXIII)101438-72-c | 150541-99-4 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-7,13-bis[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (XXIV)101438-72-c | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (XXII)101438-72-c | 75-36-5 | Acetic acid chloride |
OptimisedRoute 103Steps 2 · Total yield /
(XXV)101438-72-c,(XXV)101438-72-d115437-21-3(XXVI)101438-72-d149249-91-2(XXVII)101438-72-d135365-62-7API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (XXV)101438-72-c,(XXV)101438-72-d | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (XXVI)101438-72-d | 149249-91-2 | (3R,4S)-1-Benzoyl-4-phenyl-3-(triethylsiloxy)azetidin-2-one |
| (XXVII)101438-72-d | 135365-62-7 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1-hydroxy-9-oxo-13-([(2R,3S)-3-phenyl-3-[(phenylcarbonyl)amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
OptimisedRoute 104Steps 10 · Total yield /
(I)101438-73-a63478-76-2(II)101438-73-a—(III)101438-73-a—(IV)101438-73-a2766607-29-6(IX)101438-73-a—(V)101438-73-a—(VI)101438-73-a—(VII)101438-73-a—(VIII)101438-73-a—(X)101438-73-a—(XI)101438-73-a—(XII)101438-73-a—(XIII)101438-73-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-73-a | 63478-76-2 | Hept-6-yn-1-ol |
| (II)101438-73-a | - | 7-(Tributylstannyl)hept-6-en-1-ol |
| (III)101438-73-a | - | 3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-en-8-yl trifluoromethanesulfonate |
| (IV)101438-73-a | 2766607-29-6 | (6E)-7-(3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-en-8-yl)hept-6-en-1-ol |
| (IX)101438-73-a | - | 3-[(1E)-Hepta-1,6-dien-1-yl]-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbaldehyde |
| (V)101438-73-a | - | 8-[(1E)-7-Iodohept-1-en-1-yl]-3,3,7,7,9-pentamethyl-1,5-dioxaspiro[5.5]undec-8-ene |
| (VI)101438-73-a | - | 8-[Hepta-1,6-dien-1-yl]-3,3,7,7,9-pentamethyl-1,5-dioxaspiro[5.5]undec-8-ene |
| (VII)101438-73-a | - | 3-[(1E)-Hepta-1,6-dien-1-yl]-2,2,4-trimethylcyclohex-3-en-1-one |
| (VIII)101438-73-a | - | 3-[(1E)-Hepta-1,6-dien-1-yl]-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbonitrile |
| (X)101438-73-a | - | N'-(2-Ethenyl-2-methylcyclohexylidene)-2,4,6-tri(propan-2-yl)benzene-1-sulfonohydrazide |
| (XI)101438-73-a | - | (R)-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)[(1R)-3-[(1E)-hepta-1,6-dien-1-yl]-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-en-1-yl]methanol |
| (XII)101438-73-a | - | (1S)-1-[(S)-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)(hydroxy)methyl]-3-[(1E)-hepta-1,6-dien-1-yl]-2,2,4-trimethylcyclohex-3-en-1-ol |
| (XIII)101438-73-a | - | (4S,5S)-4-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)-7-[(1E)-hepta-1,6-dien-1-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
OptimisedRoute 105Steps 5 · Total yield /
(I)101438-74-a—(II)101438-74-a—(III)101438-74-a2766607-38-7(IV)101438-74-a—(V)101438-74-a—(VI)101438-74-a—(VII)101438-74-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-74-a | - | 3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-en-8-yl trifluoromethanesulfonate |
| (II)101438-74-a | - | 3-(Tributylstannyl)-2(E)-propen-1-ol |
| (III)101438-74-a | 2766607-38-7 | (2Z)-3-(3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-en-8-yl)prop-2-en-1-ol |
| (IV)101438-74-a | - | 3,3,7,7,9-Pentamethyl-8-[(1Z)-3-[(prop-2-en-1-yl)oxy]prop-1-en-1-yl]-1,5-dioxaspiro[5.5]undec-8-ene |
| (V)101438-74-a | - | 2,2,4-Trimethyl-3-[(1Z)-3-[(prop-2-en-1-yl)oxy]prop-1-en-1-yl]cyclohex-3-en-1-one |
| (VI)101438-74-a | - | 2,2,4-Trimethyl-3-[(1Z)-3-[(prop-2-en-1-yl)oxy]prop-1-en-1-yl]-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbonitrile |
| (VII)101438-74-a | - | 2,2,4-Trimethyl-3-[(1Z)-3-[(prop-2-en-1-yl)oxy]prop-1-en-1-yl]-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbaldehyde |
OptimisedRoute 106Steps 10 · Total yield /
(I)101438-75-a—(II)101438-75-a107-19-7(III)101438-75-a2766607-43-4(IV)101438-75-a—(IX)101438-75-a—(V)101438-75-a—(VI)101438-75-a—(VII)101438-75-a—(VIII)101438-75-a—(X)101438-75-a—(XI)101438-75-a—(XII)101438-75-a—(XIII)101438-75-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-75-a | - | 3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-en-8-yl trifluoromethanesulfonate |
| (II)101438-75-a | 107-19-7Available | 3-Hydroxy-1-propyne |
| (III)101438-75-a | 2766607-43-4 | 3-(3,3,7,7,9-Pentamethyl-1,5-dioxaspiro[5.5]undec-8-en-8-yl)prop-2-yn-1-ol |
| (IV)101438-75-a | - | 3-[(1Z)-3-Hydroxyprop-1-en-1-yl]-2,2,4-trimethylcyclohex-3-en-1-one |
| (IX)101438-75-a | - | (R*)-[(1R*)-3-(Z)-[3-[[tert-Butyl(dimethyl)silyl]oxy]prop-1-en-1-yl]-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-en-1-yl](6-ethenyl-6-methylcyclohex-1-en-1-yl)methanol |
| (V)101438-75-a | - | 3-[(1Z)-3-[[tert-Butyl(dimethyl)silyl]oxy]prop-1-en-1-yl]-2,2,4-trimethylcyclohex-3-en-1-one |
| (VI)101438-75-a | - | 3-[(1Z)-3-[[tert-Butyl(dimethyl)silyl]oxy]prop-1-en-1-yl]-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbonitrile |
| (VII)101438-75-a | - | 3-[(1Z)-3-[[tert-Butyl(dimethyl)silyl]oxy]prop-1-en-1-yl]-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbaldehyde |
| (VIII)101438-75-a | - | N'-(2-Ethenyl-2-methylcyclohexylidene)-2,4,6-tri(propan-2-yl)benzene-1-sulfonohydrazide |
| (X)101438-75-a | - | (1S*)-1-[(S*)-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)(hydroxy)methyl]-3-[3-hydroxyprop-1-en-1-yl]-2,2,4-trimethylcyclohex-3-en-1-ol |
| (XI)101438-75-a | - | 3-[(4S*,5S*)-4-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-7-yl]prop-2-en-1-yl 1H-imidazole-1-carboxylate |
| (XII)101438-75-a | - | (4S*,5S*)-4-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)-7-[3-hydroxyprop-1-en-1-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
| (XIII)101438-75-a | - | (4S*,5S*)-4-(6-Ethenyl-6-methylcyclohex-1-en-1-yl)-6,6,8-trimethyl-7-[(1E)-3-[(prop-2-en-1-yl)oxy]prop-1-en-1-yl]-1,3-dioxaspiro[4.5]dec-7-en-2-one |
OptimisedRoute 107Steps 4 · Total yield /
(I)101438-76-a2695-47-8(II)101438-76-a86-93-1(III)101438-76-a—(IV)101438-76-a—(V)101438-76-a37709-42-5(VI)101438-76-a—(VII)101438-76-a39085-59-1(VIII)101438-76-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-76-a | 2695-47-8 | 5-Hexenyl bromide |
| (II)101438-76-a | 86-93-1 | 1-Phenyltetrazoline-5-thione |
| (III)101438-76-a | - | 5-[(Hex-5-en-1-yl)sulfanyl]-1-phenyl-1H-tetrazole |
| (IV)101438-76-a | - | 5-(Hex-5-ene-1-sulfonyl)-1-phenyl-1H-tetrazole |
| (V)101438-76-a | 37709-42-5 | 1-Methyl-2-oxocyclohexane-1-carbaldehyde |
| (VI)101438-76-a | - | 2-Methyl-2-(octa-1,7-dien-1-yl)cyclohexan-1-one |
| (VII)101438-76-a | 39085-59-1 | 2,4,6-Triisopropylbenzenesulfonohydrazide |
| (VIII)101438-76-a | - | N'-[2-Methyl-2-(octa-1,7-dien-1-yl)cyclohexylidene]-2,4,6-tri(propan-2-yl)benzene-1-sulfonohydrazide |
OptimisedRoute 108Steps 5 · Total yield /
(I)101438-77-a32981-86-5(II)101438-77-a108-24-7(III)101438-77-a27548-93-2(IV)101438-77-a115437-21-3(IX)101438-77-a,(IX)101438-77-b—(V)101438-77-a79-08-3(VI)101438-77-a—(VII)101438-77-a—(VIII)101438-77-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-77-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-77-a | 108-24-7 | Acetic acid acetic anhydride |
| (III)101438-77-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-77-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IX)101438-77-a,(IX)101438-77-b | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (V)101438-77-a | 79-08-3 | 2-Bromanylethanoic acid |
| (VI)101438-77-a | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[(bromoacetyl)oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (VII)101438-77-a | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[(diazoacetyl)oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (VIII)101438-77-a | - | N-[(1Z)-Phenylmethylidene]benzamide |
OptimisedRoute 109Steps 1 · Total yield /
(I)101438-77-a32981-86-5(II)101438-77-a108-24-7(III)101438-77-a27548-93-2(IV)101438-77-a115437-21-3(IX)101438-77-a,(IX)101438-77-b—(V)101438-77-a79-08-3(VI)101438-77-a—(VII)101438-77-a—(VIII)101438-77-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-77-a | 32981-86-5 | (2alpha,5beta,7beta,10beta,13alpha)-4-(Acetyloxy)-1,7,10,13-tetrahydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (II)101438-77-a | 108-24-7 | Acetic acid acetic anhydride |
| (III)101438-77-a | 27548-93-2 | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-1,7,13-trihydroxy-9-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-77-a | 115437-21-3 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-Bis(acetyloxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate |
| (IX)101438-77-a,(IX)101438-77-b | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[[(2R,3S)-3-benzamido-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (V)101438-77-a | 79-08-3 | 2-Bromanylethanoic acid |
| (VI)101438-77-a | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[(bromoacetyl)oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (VII)101438-77-a | - | (2alpha,5beta,7beta,10beta,13alpha)-4,10-Bis(acetyloxy)-13-[(diazoacetyl)oxy]-1-hydroxy-9-oxo-7-[(triethylsilyl)oxy]-5,20-epoxytax-11-en-2-yl benzoate |
| (VIII)101438-77-a | - | N-[(1Z)-Phenylmethylidene]benzamide |
OptimisedRoute 110Steps 8 · Total yield /
(I)101438-78-a10316-61-7(II)101438-78-a—(III)101438-78-a39085-59-1(IV)101438-78-a—(IX)101438-78-a—(V)101438-78-a—(VI)101438-78-a—(VII)101438-78-a—(VIII)101438-78-a—(X)101438-78-a—(XI)101438-78-a—(XII)101438-78-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-78-a | 10316-61-7 | 2-(Hydroxymethyl)-2-methylcyclohexan-1-one |
| (II)101438-78-a | - | 2-[(Ethoxymethoxy)methyl]-2-methylcyclohexan-1-one |
| (III)101438-78-a | 39085-59-1 | 2,4,6-Triisopropylbenzenesulfonohydrazide |
| (IV)101438-78-a | - | N'-[2-[(Ethoxymethoxy)methyl]-2-methylcyclohexylidene]-2,4,6-tri(propan-2-yl)benzene-1-sulfonohydrazide |
| (IX)101438-78-a | - | (4S*,5S*)-7-Ethenyl-4-[(6S*)-6-(hydroxymethyl)-6-methylcyclohex-1-en-1-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
| (V)101438-78-a | - | (1S*)-3-Ethenyl-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-ene-1-carbaldehyde |
| (VI)101438-78-a | - | (S*)-[(1S*)-3-Ethenyl-2,2,4-trimethyl-1-[(trimethylsilyl)oxy]cyclohex-3-en-1-yl][(6R)-6-[(ethoxymethoxy)methyl]-6-methylcyclohex-1-en-1-yl]methanol |
| (VII)101438-78-a | - | (1S*)-3-Ethenyl-1-[(S*)-[(6R*)-6-[(ethoxymethoxy)methyl]-6-methylcyclohex-1-en-1-yl](hydroxy)methyl]-2,2,4-trimethylcyclohex-3-en-1-ol |
| (VIII)101438-78-a | - | (4S*,5S*)-7-Ethenyl-4-[(6S*)-6-[(ethoxymethoxy)methyl]-6-methylcyclohex-1-en-1-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
| (X)101438-78-a | - | (1R*)-2-[(4S*,5S*)-7-Ethenyl-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-4-yl]-1-methylcyclohex-2-ene-1-carbaldehyde |
| (XI)101438-78-a | - | 5-(Hex-5-ene-1-sulfonyl)-1-phenyl-1H-tetrazole |
| (XII)101438-78-a | - | (4S*,5S*)-7-Ethenyl-4-[(6S*)-6-[hepta-1,6-dien-1-yl]-6-methylcyclohex-1-en-1-yl]-6,6,8-trimethyl-1,3-dioxaspiro[4.5]dec-7-en-2-one |
OptimisedRoute 111Steps 3 · Total yield /
(I)101438-79-a111-45-5(II)101438-79-a86-93-1(III)101438-79-a—(IV)101438-79-a—(V)101438-79-a—(VI)101438-79-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-79-a | 111-45-5 | 2-[(Prop-2-en-1-yl)oxy]ethan-1-ol |
| (II)101438-79-a | 86-93-1 | 1-Phenyltetrazoline-5-thione |
| (III)101438-79-a | - | 1-Phenyl-5-([2-[(prop-2-en-1-yl)oxy]ethyl]sulfanyl)-1H-tetrazole |
| (IV)101438-79-a | - | 1-Phenyl-5-[2-[(prop-2-en-1-yl)oxy]ethanesulfonyl]-1H-tetrazole |
| (V)101438-79-a | - | (1R*)-2-[(4S*,5S*)-7-Ethenyl-6,6,8-trimethyl-2-oxo-1,3-dioxaspiro[4.5]dec-7-en-4-yl]-1-methylcyclohex-2-ene-1-carbaldehyde |
| (VI)101438-79-a | - | (4S*,5S*)-7-Ethenyl-6,6,8-trimethyl-4-[(6S*)-6-methyl-6-[3-[(prop-2-en-1-yl)oxy]prop-1-en-1-yl]cyclohex-1-en-1-yl]-1,3-dioxaspiro[4.5]dec-7-en-2-one |
OptimisedRoute 112Steps 6 · Total yield /
(I)101438-80-a142203-65-4(II)101438-80-a—(III)101438-80-a—(IV)101438-80-a—(V)101438-80-a—(VI)101438-80-a143527-70-2(VII)101438-80-a—(VIII)101438-80-a—API · Paclitaxel
| Code | CAS No. | Intermediate |
|---|---|---|
| (I)101438-80-a | 142203-65-4 | 13-Acetyl-9-dihydrobaccatin-III |
| (II)101438-80-a | - | (2alpha,5beta,7beta,9alpha,10beta,13alpha)-4,13-Bis(acetyloxy)-1,7,9,10-tetrahydroxy-5,20-epoxytax-11-en-2-yl benzoate |
| (III)101438-80-a | - | (2alpha,5beta,7beta,9alpha,10beta,13alpha)-4,13-Bis(acetyloxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-1,9,10-trihydroxy-5,20-epoxytax-11-en-2-yl benzoate |
| (IV)101438-80-a | - | (2alpha,5beta,7beta,9alpha,13alpha)-4,13-Bis(acetyloxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-1,9-dihydroxy-10-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (V)101438-80-a | - | (2alpha,5beta,7beta,9alpha,13alpha)-4-(Acetyloxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-1,9,13-trihydroxy-10-oxo-5,20-epoxytax-11-en-2-yl benzoate |
| (VI)101438-80-a | 143527-70-2 | (4S,5R)-3-(tert-Butoxycarbonyl)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-5-carboxylic acid |
| (VII)101438-80-a | - | 5-[(2alpha,5beta,7beta,9alpha,13alpha)-4-(Acetyloxy)-2-(benzoyloxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-1,9-dihydroxy-10-oxo-5,20-epoxytax-11-en-13-yl] 3-tert-butyl (4S)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate |
| (VIII)101438-80-a | - | (2alpha,5beta,7beta,9alpha,13alpha)-4-(Acetyloxy)-13-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1,7,9-trihydroxy-10-oxo-5,20-epoxytax-11-en-2-yl benzoate |
Frequently asked questions
What are the approved indications of Paclitaxel?
Approved indications include: Pancreatic cancer, Non-small cell lung cancer, Hodgkin's disease, Seminoma, Ovarian cancer, Breast cancer, Oesophageal cancer, Head and neck cancer.
When does the Paclitaxel patent expire?
No public expiry year is available for Paclitaxel yet; this page updates once verified.
How many synthesis routes are recorded for Paclitaxel?
112 synthesis routes are recorded; the shortest is 1 steps with / total yield. Intermediates in each route carry codes and CAS numbers.
Where can I buy Paclitaxel intermediates?
17 intermediate CAS of Paclitaxel are available through the Unibest supply network — see the route tables on this page and request a quote per CAS.
How do I get a quote for Paclitaxel intermediates?
Open the CAS profile of the target intermediate from this page, or submit an RFQ directly — the CAS enters the matching flow automatically and the supply network responds with quotes.
Source: cross-verified data (structured fields only) · 2026-09-29