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【结 构 式】 
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【药物名称】 【化学名称】[2aR,4S,4aS,6R,9S(alphaR,betaS),11S,12S,12aR,12bS]-beta-(Benzoylamino)-alpha-hydroxybenzenepropanoic acid 6,12b-bis(acetoxy)-4-[3-[2-[3H]-3-(benzoyl)phenyl]propanoyloxy]-12-(benzoyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-11-hydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methano-1H-cyclodeca[3,4]benz[1,2-b]oxet-9-yl ester 【CA登记号】 【 分 子 式 】C63H63NO16 【 分 子 量 】1090.20166 |
【开发单位】State University of New York,Stony Brook (Originator) 【药理作用】ONCOLYTIC DRUGS, Taxanes |
合成路线1
Selective protection of the 7-hydroxyl group of deacetylbaccatin (I) with triethylsilyl chloride provided silyl ether (II), which was acetylated at position 10 using acetyl chloride and lithium hexamethyldisilazide. Further coupling of (II) with beta-lactam (III) gave (IV), which by selective removal of the 7-silyl group with 0.1 N HCl gave 10-acetyl-2'-(triisopropylsilyl)docetaxel (V). This was condensed with benzoylcinnamic acid (VI) employing EDC and DMAP to afford ester (VII).
| 【1】 Ahern, D.G.; Ojima, I.; Bounaud, P.-Y.; New photoaffinity analogs of paclitaxel. Bioorg Med Chem Lett 1999, 9, 8, 1189. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 25331 | 3-hydroxyacetophenone; 1-(3-hydroxyphenyl)-1-ethanone | 121-71-1 | C8H8O2 | 详情 | 详情 |
| (II) | 25332 | (E)-3-(3,4-dimethoxyphenyl)-1-(3-hydroxyphenyl)-2-propen-1-one | C17H16O4 | 详情 | 详情 | |
| (III) | 25333 | tert-butyl (3R,4S)-2-oxo-4-phenyl-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate | C23H37NO4Si | 详情 | 详情 | |
| (IV) | 25334 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)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)]h | C60H89NO15Si2 | 详情 | 详情 | |
| (V) | 25335 | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]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 | C54H75NO15Si | 详情 | 详情 | |
| (VI) | 25336 | (E)-3-(3-benzoylphenyl)-2-propenoic acid | C16H12O3 | 详情 | 详情 | |
| (VII) | 25337 | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[1 | C70H85NO17Si | 详情 | 详情 |
合成路线2
The triisopropylsilyl group at position 2' of (VII) was deprotected with HF in pyridine-acetonitrile yielding (VIII), and the Boc group was further removed with trifluoroacetic acid to give (IX). Then, benzoylation of the 3'-amino group of (IX) with benzoyl chloride provided benzamide (X). Finally, hydrogenation of the cinnamyl double bond of (X) in the presence of Wilkinson's catalyst furnished the target compound.
| 【1】 Ahern, D.G.; Ojima, I.; Bounaud, P.-Y.; New photoaffinity analogs of paclitaxel. Bioorg Med Chem Lett 1999, 9, 8, 1189. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 25337 | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-phenyl-2-[(triisopropylsilyl)oxy]propanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[1 | C70H85NO17Si | 详情 | 详情 | |
| (VIII) | 25338 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]oxy]-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4 | C61H65NO17 | 详情 | 详情 | |
| (IX) | 25339 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]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 | C56H57NO15 | 详情 | 详情 | |
| (X) | 25340 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-9-[[(E)-3-(3-benzoylphenyl)-2-propenoyl]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 | C63H61NO16 | 详情 | 详情 |