Enantioselective Total Synthesis of (+)-Largazole, a Potent Inhibitor of Histone Deacetylase
Organic Letters2008Vol. 10(17), pp. 3907–3909
Citations Over TimeTop 10% of 2008 papers
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.
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