Enantioselective total synthesis of (+)-scyphostatin, a potent and specific inhibitor of neutral sphingomyelinase
Enantioselective total synthesis of (+)-scyphostatin, a potent and specific inhibitor of neutral sphingomyelinase
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DOI：
10.1055/s-2007-965893
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发表时间：
2007-02-15
影响因子：
2.6
通讯作者：
Katoh, Tadashi
中科院分区：
文献类型：
--
作者：
Inoue, Munenori;Yokota, Wakako;Katoh, Tadashi
以D-阿拉伯糖和3-羟基-2-甲基丙酸甲酯的两种对映体为起始原料，首次完成了（+）-scyphostatin的全合成。该方法包括（a）1，3-二氧戊环-4-羧酸甲酯与Garner醛的立体选择性羟醛偶联以在C4上建立不对称季碳中心，（B）所得二烯的闭环复分解以构建环己烯环，（c）乙烯基碘和烷基碘的Negishi偶联以形成所需的三取代E-烯烃，（d）由环己烯链段和三取代的E-烯烃脂肪酸链段形成酰胺，和（e）由两个链段形成的酰胺的甲磺酸酯立体有择地形成环氧环。
The total synthesis of (+)-scyphostatin, a specific and potent neutral sphingomyclinase inhibitor from a microorganism, was accomplished for the first time starting from D-arabinose and both enantiomers of methyl 3-hydroxy-2-methylpropionate. The method involves (a) stereoselective aldol coupling of a methyl 1,3-dioxolane-4-carboxylate with the Garner aldehyde to establish the asymmetric quaternary carbon center at C4, (b) ring-closing metathesis of the resultant diene to construct the cyclohexene ring, (c) Negishi coupling of a vinyl iodide and an alkyl iodide to form the requisite trisubstituted E-alkene, (d) formation of an amide from the cyclohexene segment and the trisubstituted E-alkene fatty acid segment, and (e) stereospecific formation of an epoxide ring from the mesylate of the amide formed from the two segments.