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【结 构 式】 
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【分子编号】56388 【品名】(2R,4R,6S,7R,10R,13S,14R,15S,16S,18S)-13-(acetyloxy)-18-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-(3-fluoro-2-pyridinyl)-2-[(triisopropylsilyl)oxy]propanoyl}oxy)-16-hydroxy-7,19,20,20-tetramethyl-4-vinyl-3,5,11-trioxapentacyclo[14.3.1.0~2,6~.0~7,14~.0~10,13~]icos-1(19)-en-15-yl benzoate 【CA登记号】 |
【 分 子 式 】C54H75FN2O13Si 【 分 子 量 】1007.2790832 【元素组成】C 64.39% H 7.5% F 1.89% N 2.78% O 20.65% Si 2.79% |
合成路线1
该中间体在本合成路线中的序号：(III)The title taxane derivative is prepared by two related ways. Taxane (I) is condensed with azetidinone (II) in the presence of lithium hexamethyldisilazide to afford ester (III). The triisopropylsilyl protecting group of (III) is then removed by using a solution of tetrabutylammonium fluoride in THF, yielding (IV). Dihydroxylation of the vinyl group of (IV) with N-methylmorpholine N-oxide in the presence of osmium tetroxide produces diol (V), which is subsequently cleaved to aldehyde (VI) by means of NaIO4. Finally, reductive amination of aldehyde (VI) with dimethylamine and NaBH3CN gives rise to the target amine.
| 【1】 Soga, T.; Takeda, Y.; Uoto, K. (Daiichi Pharmaceutical Co., Ltd.); Pentacyclic taxane cpds.. EP 1221445; WO 0127115 . |
| 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) | 56386 | (2R,4R,6S,7R,10R,13S,14R,15S,16S,18S)-13-(acetyloxy)-16,18-dihydroxy-7,19,20,20-tetramethyl-4-vinyl-3,5,11-trioxapentacyclo[14.3.1.0~2,6~.0~7,14~.0~10,13~]icos-1(19)-en-15-yl benzoate | C32H40O9 | 详情 | 详情 | |
| (II) | 56387 | tert-butyl (2S,3R)-2-(3-fluoro-2-pyridinyl)-4-oxo-3-[(triisopropylsilyl)oxy]-1-azetidinecarboxylate | C22H35FN2O4Si | 详情 | 详情 | |
| (III) | 56388 | (2R,4R,6S,7R,10R,13S,14R,15S,16S,18S)-13-(acetyloxy)-18-({(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-(3-fluoro-2-pyridinyl)-2-[(triisopropylsilyl)oxy]propanoyl}oxy)-16-hydroxy-7,19,20,20-tetramethyl-4-vinyl-3,5,11-trioxapentacyclo[14.3.1.0~2,6~.0~7,14~.0~10,13~]icos-1(19)-en-15-yl benzoate | C54H75FN2O13Si | 详情 | 详情 | |
| (IV) | 56389 | (2R,4R,6S,7R,10R,13S,14R,15S,16S,18S)-13-(acetyloxy)-18-{[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-(3-fluoro-2-pyridinyl)-2-hydroxypropanoyl]oxy}-16-hydroxy-7,19,20,20-tetramethyl-4-vinyl-3,5,11-trioxapentacyclo[14.3.1.0~2,6~.0~7,14~.0~10,13~]icos-1(19)-en-15-yl benzoate | C45H55FN2O13 | 详情 | 详情 | |
| (V) | 56390 | (2R,4R,6S,7R,10R,13S,14R,15S,16S,18S)-13-(acetyloxy)-18-{[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-(3-fluoro-2-pyridinyl)-2-hydroxypropanoyl]oxy}-4-[(1R)-1,2-dihydroxyethyl]-16-hydroxy-7,19,20,20-tetramethyl-3,5,11-trioxapentacyclo[14.3.1.0~2,6~.0~7,14~.0~10,13~]icos-1(19)-en-15-yl benzoate | C45H57FN2O15 | 详情 | 详情 | |
| (VI) | 56391 | (2R,4R,6S,7R,10R,13S,14R,15S,16S,18S)-13-(acetyloxy)-18-{[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-3-(3-fluoro-2-pyridinyl)-2-hydroxypropanoyl]oxy}-4-formyl-16-hydroxy-7,19,20,20-tetramethyl-3,5,11-trioxapentacyclo[14.3.1.0~2,6~.0~7,14~.0~10,13~]icos-1(19)-en-15-yl benzoate | C44H53FN2O14 | 详情 | 详情 |