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【结 构 式】 
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【分子编号】36568 【品名】tert-butyl (2S,3R,4E)-3-[[(benzyloxy)carbonyl]amino]-2-[(4-methoxybenzyl)sulfanyl]-5-[(neopentyloxy)sulfonyl]-4-pentenoate 【CA登记号】 |
【 分 子 式 】C30H41NO8S2 【 分 子 量 】607.78948 【元素组成】C 59.29% H 6.8% N 2.3% O 21.06% S 10.55% |
合成路线1
该中间体在本合成路线中的序号：(V)Esterification of N-(benzyloxycarbonyl)-L-aspartic acid beta-tert-butyl ester (I) by means of diazomethane provided the alpha-methyl ester (II), which was subsequently sulfenylated using (2,4-dinitrophenyl)-(4-methoxybenzyl)disulfide (III) in the presence of n-BuLi to furnish the (2R,3R)-sulfide (IV) as the major isomer. Reduction of the methyl ester group of (IV) with DIBAL, followed by Wittig-Horner reaction of a postulated aldehyde aluminoxyacetal intermediate with neopentyl diethoxyphosphoryl methanesulfonate produced the alpha,beta-unsaturated sulfonate ester (V). Reduction of the double bond of (V) employing [(PPh3)CuH]6 in neutral medium afforded the saturated ester (VI) with only a small epimerization at the C2 position. The tert-butyl ester of (VI) was then deprotected with trifluoroacetic acid yielding the free acid (VII).
| 【1】 Davis, C.; Bischoff, L.; Meudal, H.; et al.; Investigation of subsite preferences in aminopeptidase A (EC 3.4.11.7) led to the design of the first highly potent and selective inhibitors of this enzyme. J Med Chem 1999, 42, 25, 5197. |
| 【2】 Fournie-Zaluski, M.-C.; Roques, B.; David, C.; Bischoff, L.; Llorens-Cortes, C. (CNRS (Centre National de la Recherche Scientifique); INSERM (Institut National de la Sante et de la Recherche Medicale)); Tripeptide cpds. useful as selective inhibitors of aminopeptidase A and corresponding pharmaceutical compsns.. FR 2788526; WO 0043414 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 40723 | neopentyl (diethoxyphosphoryl)methanesulfonate | C10H23O6PS | 详情 | 详情 | ||
| (I) | 36564 | (2S)-2-[[(benzyloxy)carbonyl]amino]-4-(tert-butoxy)-4-oxobutyric acid | C16H21NO6 | 详情 | 详情 | |
| (II) | 36565 | 4-(tert-butyl) 1-methyl (2S)-2-[[(benzyloxy)carbonyl]amino]butanedioate | C17H23NO6 | 详情 | 详情 | |
| (III) | 36566 | 1-[(4-methoxybenzyl)disulfanyl]-2,4-dinitrobenzene; 2,4-dinitrophenyl 4-methoxybenzyl disulfide | C14H12N2O5S2 | 详情 | 详情 | |
| (IV) | 36567 | 4-(tert-butyl) 1-methyl (2R,3S)-2-[[(benzyloxy)carbonyl]amino]-3-[(4-methoxybenzyl)sulfanyl]butanedioate | C25H31NO7S | 详情 | 详情 | |
| (V) | 36568 | tert-butyl (2S,3R,4E)-3-[[(benzyloxy)carbonyl]amino]-2-[(4-methoxybenzyl)sulfanyl]-5-[(neopentyloxy)sulfonyl]-4-pentenoate | C30H41NO8S2 | 详情 | 详情 | |
| (VI) | 36569 | tert-butyl (2S,3R)-3-[[(benzyloxy)carbonyl]amino]-2-[(4-methoxybenzyl)sulfanyl]-5-[(neopentyloxy)sulfonyl]pentanoate | C30H43NO8S2 | 详情 | 详情 | |
| (VII) | 36570 | (2S,3R)-3-[[(benzyloxy)carbonyl]amino]-2-[(4-methoxybenzyl)sulfanyl]-5-[(neopentyloxy)sulfonyl]pentanoic acid | C26H35NO8S2 | 详情 | 详情 |