高效组蛋白去乙酰化酶抑制剂（+）-largazole的对映选择性全合成。
Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase.
作者信息
Ghosh Arun K, Kulkarni Sarang
机构信息
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
出版信息
Org Lett. 2008 Sep 4;10(17):3907-9. doi: 10.1021/ol8014623. Epub 2008 Jul 29.
Abstract
An enantioselective total synthesis of the cytotoxic natural product (+)-largazole (1) is described. It is a potent histone deacetylase inhibitor. Our synthesis is convergent and involves the assembly of thiazole 3-derived carboxylic acid with amino ester 4 followed by cycloamidation of the corresponding amino acid. The synthesis features an efficient cross-metathesis, an enzymatic kinetic resolution of a beta-hydroxy ester, a selective removal of a Boc-protecting group, a HATU/HOAt-promoted cycloamidation reaction, and synthetic manipulations to a sensitive thioester functional group.
摘要
描述了细胞毒性天然产物(+)-拉加唑(1)的对映选择性全合成。它是一种有效的组蛋白脱乙酰酶抑制剂。我们的合成是汇聚式的，涉及噻唑3衍生的羧酸与氨基酯4的组装，随后是相应氨基酸的环酰胺化。该合成的特点包括高效的交叉复分解反应、β-羟基酯的酶促动力学拆分、Boc保护基的选择性去除、HATU/HOAt促进的环酰胺化反应以及对敏感硫酯官能团的合成操作。
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