Enantioselective Total Synthesis of (+)-Largazole, a Potent Inhibitor of Histone Deacetylase
- 29 July 2008
- journal article
- letter
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 10 (17) , 3907-3909
- https://doi.org/10.1021/ol8014623
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 β-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.Keywords
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