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Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase.

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.

SUBMITTER: Ghosh AK 

PROVIDER: S-EPMC2945909 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase.

Ghosh Arun K AK   Kulkarni Sarang S  

Organic letters 20080729 17

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 cyc  ...[more]

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