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【结 构 式】 
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【分子编号】43823 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-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 【CA登记号】 |
【 分 子 式 】C34H48O11Si 【 分 子 量 】660.83402 【元素组成】C 61.8% H 7.32% O 26.63% Si 4.25% |
合成路线1
该中间体在本合成路线中的序号：(III)A novel semisynthetic method for the production of paclitaxel from 10-deacetylbaccantin-III using dialkyldichlorosilanes has been reported: The protection of the 7-OH of 10-deacetylbaccatin-III (I) by reaction first with dichlorodiethylsilane (II) and imidazole and then with methanol gives 7-O-[diethyl(methoxy)silyl]baccatin-III (III), which is regioselectively acetylated at the 10-OH with acetylimidazole and LiHMDS to yield the acetate (IV). The esterification of (IV) with the chiral oxazolinecarboxylic acid (V) by means of LiHMDS affords the corresponding ester (VI), which is treated with TFA in HOAc/water in order to perform desilylation and open the oxazoline ring to furnish paclitaxel. Other silylating agents, such as dimethyldichlorosilane, dipropyldichlorosilane, diisopropyldichlorosilane, dibutyldichlorosilane and diphenyldichlorosilane, and other alcohols, such as EtOH, PrOH, i-PrOH, t-BuOH, 3,3,3-trifluoroethanol and others, can also be used in the silylation step.
| 【1】 Dillon, J.L. Jr.; Vemishetti, P.; Gibson, F.S. (Bristol-Myers Squibb Co.); Semi-synthesis of paclitaxel using dialkyldichlorosilanes. WO 0073293 . |
| 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) | 10467 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-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 | 32981-86-5 | C29H36O10 | 详情 | 详情 |
| (II) | 43822 | dichloro(diethyl)silane | 1719-53-5 | C4H10Cl2Si | 详情 | 详情 |
| (III) | 43823 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-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 | C34H48O11Si | 详情 | 详情 | |
| (IV) | 43824 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-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 | C36H50O12Si | 详情 | 详情 | |
| (V) | 10597 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid | C16H13NO3 | 详情 | 详情 | |
| (VI) | 43825 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-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-carb | C52H61NO14Si | 详情 | 详情 |