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【结 构 式】 
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【分子编号】10589 【品名】(1S,5S,6R,10R,12S,13R,15R,18S)-12-[(benzyloxy)methyl]-18-[[tert-butyl(dimethyl)silyl]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 【CA登记号】 |
【 分 子 式 】C37H54O9Si 【 分 子 量 】670.91586 【元素组成】C 66.24% H 8.11% O 21.46% Si 4.19% |
合成路线1
该中间体在本合成路线中的序号：(XXXII)The secondary alcohol (XXXII) is treated with phenyllithium in THF (to open the cyclic carbonate and form the benzoyloxy group) and oxidized with tetrapropylammonium perruthenate (TPAP) to give the benzoyloxyketone (XXXIII). Enolization of ketone (XXXIII) with potassium tert-butoxide affords the potassium enolate (XXXIV), which is oxidized with phenylseleninic anhydride and acetylated with acetic anhydride in DMAP to give the alpha-acetoxyketone (XXXV). Further desilylation of (XXXV) with tris(diethylamino)sulfoxonium difluorotrimethylsiliconate (TASF) in THF yields the secondary alcohol (XXXVI), which is condensed with Ojima's beta-lactam (XXXVII) by means of lithium hexamethyldisilazane (LHMDS) in THF to afford protected paclitaxel (XXXVIII). Finally, this compound is deprotected first with HF in pyridine to eliminate the triethylsilyl (TES) group and then hydrogenated with H2 over Pd/C in ethanol to eliminate the BOM group.
| 【1】 Kim, H.-B.; Holton, R.A.; Somoza, C.; et al.; First total synthesis of taxol. 2. Completion of the C and D rings. J Am Chem Soc 1994, 116, 4, 1599. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXXII) | 10589 | (1S,5S,6R,10R,12S,13R,15R,18S)-12-[(benzyloxy)methyl]-18-[[tert-butyl(dimethyl)silyl]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 | C37H54O9Si | 详情 | 详情 | |
| (XXXIII) | 10590 | (1S,2S,3R,4S,7R,9S,10R,15S)-4-(acetoxy)-9-[(benzyloxy)methyl]-15-[[tert-butyl(dimethyl)silyl]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 | C43H58O9Si | 详情 | 详情 | |
| (XXXIV) | 10591 | potassium (1S,2S,3R,4S,7R,9S,10S,15S)-4-(acetoxy)-2-(benzoyloxy)-9-[(benzyloxy)methyl]-15-[[tert-butyl(dimethyl)silyl]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 | C43H57KO9Si | 详情 | 详情 | |
| (XXXV) | 10592 | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-9-[(benzyloxy)methyl]-15-[[tert-butyl(dimethyl)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-2-yl benzoate | C45H60O11Si | 详情 | 详情 | |
| (XXXVI) | 10593 | (1S,2S,3R,4S,7R,9S,10R,12R,15S)-4,12-bis(acetoxy)-9-[(benzyloxy)methyl]-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 | C39H46O11 | 详情 | 详情 | |
| (XXXVII) | 10490 | (3R,4S)-1-Benzoyl-4-phenyl-3-[(triethylsilyl)oxy]-2-azetanone | C22H27NO3Si | 详情 | 详情 | |
| (XXXVIII) | 10595 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-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 | 33069-62-4 | C47H51NO14 | 详情 | 详情 |