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【结 构 式】 
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【分子编号】10710 【品名】(1S,4S,5S,7R,11R,12S,16S,19R)-4,19,21,21-tetramethyl-2-methylene-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)]henicos-10-yl acetate 【CA登记号】 |
【 分 子 式 】C30H46O8Si 【 分 子 量 】562.77594 【元素组成】C 64.03% H 8.24% O 22.74% Si 4.99% |
合成路线1
该中间体在本合成路线中的序号：(XIX)Epoxide (XVIII) is debenzylated by hydrogenation and acetylated with acetic anhydride and dimethylaminopyridine (DMAP) to compound (XIX). The ring opening of the cyclic carbonate group of (XIX) with phenyllithium affords compound (XX) with the secondary benzoate group and the tertiary hydroxy substituent of paclitaxel. The oxidation of the methylene group of (XX) with OsO4 and lead tetraacetate affords the epoxy ketone (XXI). The deoxygenation of the epoxy group of (XXI) is performed with SmI2 and acetic anhydride, and after oxidation, alpha-ketol interchange and acetylation, compound (XXII) with almost all the functionality of paclitaxel is obtained. The allylic oxidation of (XXII) with pyridinium chlorochromate (PCC) followed by reduction with NaBH4 affords triethylsilyl-baccatin III (XXIII), which is deprotected with HF.pyridine to baccatin III (XXIV). Finally, both compounds (XXIII) and (XXIV) are converted to paclitaxel by known methods (J Org Chem 1991, 56: 1681).
| 【1】 Masters, J.J.; Young, W.B.; Snyder, L.B.; Link, J.T.; Danishefsky, S.J.; A total synthesis of Taxol. Angew Chem. Int Ed Engl 1995, 34, 16, 1723. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 10709 | (1S,4S,5S,7R,10S,11R,12S,16S,19R)-10-(Benzyloxy)-4,19,21,21-tetramethyl-2-methylene-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 | C35H50O7Si | 详情 | 详情 | |
| (XIX) | 10710 | (1S,4S,5S,7R,11R,12S,16S,19R)-4,19,21,21-tetramethyl-2-methylene-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)]henicos-10-yl acetate | C30H46O8Si | 详情 | 详情 | |
| (XX) | 10711 | (1S,4S,5S,7R,10S,11R,12S,13S,16R)-10-(acetoxy)-13-hydroxy-4,16,18,18-tetramethyl-2-methylene-5-[(triethylsilyl)oxy]-8,17-dioxapentacyclo[11.4.1.0(1,16).0(4,11).0(7,10)]octadec-12-yl benzoate | C36H52O8Si | 详情 | 详情 | |
| (XXI) | 10712 | (1S,4S,5S,7R,10S,11R,12S,13S,16R)-10-(acetoxy)-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)]octadec-12-yl benzoate | C35H50O9Si | 详情 | 详情 | |
| (XXII) | 10531 | (1S,2S,3R,4S,7R,9S,10S,12R)-4,12-bis(acetoxy)-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 | C37H52O10Si | 详情 | 详情 | |
| (XXIII) | 10473 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-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 | C37H52O11Si | 详情 | 详情 | |
| (XXIV) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-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 | C31H38O11 | 详情 | 详情 |