Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR
Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR
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DOI：
10.1021/ja049821k
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发表时间：
2004-05-26
影响因子：
15
通讯作者：
Danishefsky, SJ
中科院分区：
文献类型：
--
作者：
Lin, SN;Yang, ZQ;Danishefsky, SJ
提供了蛋白酶体抑制剂TMC-95A和-B的全合成的完整说明。合成的一个关键特征是通过对α -硅烯丙烯酰胺的热重排来安装顺式丙烯酰胺。讨论了成瓷反应的范围和机理。本文还提供了SAR研究的一些初步结果。研究发现，简化的类似物可以保留蛋白酶体抑制的全部效力。
A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an alpha-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.