【结 构 式】 |
【药物名称】TAX-258, XRP-6258, RPR-116258A, TXD-258 【化学名称】[2aR[2aalpha,4beta,4abeta,6beta,9alpha(2R,3S),11beta,12alpha,12aalpha,12balpha]]-12b-Acetoxy-9-[3-(tert-butoxycarbonylamino)-2-hydroxy-3-phenylpropionyloxy]-12-(benzoyloxy)-11-hydroxy-4,6-dimethoxy-4a,8,13,13-tetramethyl-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-5-one 【CA登记号】183133-96-2 【 分 子 式 】C45H57NO14 【 分 子 量 】835.95434 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Breast Cancer Therapy, Oncolytic Drugs, Antimitotic Drugs, Microtubule-Stabilizing Agents, Taxanes |
合成路线1
Protection of 10-deacetylbaccatin III (I) with chlorotriethylsilane in pyridine affords the 7,13-bis-silyl ether (II), which upon alkylation by means of iodomethane and NaH provides the 10-methoxy derivative (III). After desilylation of (III) by means of a hydrogen fluoride-triethylamine complex, the deprotected triol (IV) is methylated with iodomethane and NaH to yield the 7,10-dimethyl ether (V). Esterification of (V) with the oxazolidinecarboxylic acid (VI) in the presence of DCC/DMAP furnishes (VII). (1,2)
【1】 Bouchard, H.; Bourzat, J.-D.; Commerçon, A. (Aventis Pharma SA); Novel taxoids, preparation thereof and pharmaceutical compsns. containing same. EP 0817779; EP 0817780; FR 2732340; JP 1999500141; JP 1999502531; US 5889043; US 6372780; US 6387946; WO 9630355; WO 9630356 . |
【2】 Bissery, M.-C. (Aventis Pharma SA); Use of taxoid derivs.. EP 1020188; EP 1140064; US 2002082291; US 6403634; WO 0041482 . |
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) | 64863 | 4-(acetyloxy)-1,9,12,15-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 | C29H36O10 | 详情 | 详情 | |
(II) | 64864 | C41H64O10Si2 | 详情 | 详情 | ||
(III) | 64865 | C42H66O10Si2 | 详情 | 详情 | ||
(IV) | 64866 | C30H38O10 | 详情 | 详情 | ||
(V) | 64867 | C31H40O10 | 详情 | 详情 | ||
(VI) | 64868 | 3-{[(1,1-dimethylethyl)oxy]carbonyl}-2-[4-(methyloxy)phenyl]-4-phenyl-1,3-oxazolidine-5-carboxylic acid | C22H25NO6 | 详情 | 详情 | |
(VII) | 64869 | C53H63NO15 | 详情 | 详情 |
合成路线2
Selective hydrolysis of the oxazolidine moiety of (VII) under smooth acidic conditions gives yields the hydroxy amino ester derivative. (1,2)
【1】 Bouchard, H.; Bourzat, J.-D.; Commerçon, A. (Aventis Pharma SA); Novel taxoids, preparation thereof and pharmaceutical compsns. containing same. EP 0817779; EP 0817780; FR 2732340; JP 1999500141; JP 1999502531; US 5889043; US 6372780; US 6387946; WO 9630355; WO 9630356 . |
【2】 Bissery, M.-C. (Aventis Pharma SA); Use of taxoid derivs.. EP 1020188; EP 1140064; US 2002082291; US 6403634; WO 0041482 . |
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) | 64869 | C53H63NO15 | 详情 | 详情 |
合成路线3
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) | 64863 | 4-(acetyloxy)-1,9,12,15-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 | C29H36O10 | 详情 | 详情 | |
(II) | 64867 | C31H40O10 | 详情 | 详情 | ||
(III) | 54908 | (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoic acid | 136561-53-0 | C9H11NO3 | 详情 | 详情 |
(IV) | 67065 | (2R,3S)-3-((tert-butoxycarbonyl)amino)-2-hydroxy-3-phenylpropanoic acid | C14H19NO5 | 详情 | 详情 |