Enantioselective synthesis of the protein phosphatase inhibitor (-)-motuporin
Enantioselective synthesis of the protein phosphatase inhibitor (-)-motuporin
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DOI：
10.1021/ja0206700
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发表时间：
2002-09-25
影响因子：
15
通讯作者：
Panek, JS
中科院分区：
文献类型：
--
作者：
Hu, T;Panek, JS
描述了一种高度收敛的蛋白质磷酸酶抑制剂Motuporin 1a的不对称合成方法。单肽片段[34+35-->；51]的合成和偶联，然后进行大环化，得到完全保护的motuporin前体33，该前体通过脱水和酯水解法转化为天然产物。与天然产物相关的8个立体中心中的6个是使用不对称巴豆基硅烷键构建方法引入的。我们的方法的特点是在Pd(0)催化下，在构型良好的乙烯基锌中间体22和(E)-乙烯基碘化合物7之间进行高效的交叉偶联反应，得到化合物43，从而构建了Motuporin侧链的三取代(EE)-二烯体系，改进了形成33的大环化反应条件。
A highly convergent asymmetric synthesis of the protein phosphatase inhibitor motuporin 1a is described. Synthesis and coupling of the individual peptide fragments [34 + 35 --> 51] followed by macrocyclization afforded the fully protected motuporin precursor 33, which is converted to the natural product by dehydration and ester hydrolysis. Six of the eight stereogenic centers associated with the natural product were introduced using asymmetric crotylsilane bond construction methodology. Our approach features an efficient Pd(0)-catalyzed cross-coupling reaction between a configurationally well-defined vinyl zinc intermediate 22 and an (E)-vinyl iodide 7, which afforded compound 43, resulting in the construction of the trisubstituted (EE)-diene system of the motuporin side chain Improved reaction conditions for macrocyclization in the formation of 33 are also detailed.