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Total synthesis of tetrahydrolipstatin and stereoisomers via a highly regio- and diastereoselective carbonylation of epoxyhomoallylic alcohols.

ABSTRACT: A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid](+)[Co(CO)4](-) catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone. The success of this route to THL and its stereoisomers also demonstrated the practicality of the carbonylation catalyst for complex molecule synthesis as well as its functional group compatibility.

SUBMITTER: Mulzer M

PROVIDER: S-EPMC4120994 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Total synthesis of tetrahydrolipstatin and stereoisomers via a highly regio- and diastereoselective carbonylation of epoxyhomoallylic alcohols.

Mulzer Michael M Tiegs Brandon J BJ Wang Yanping Y Coates Geoffrey W GW O'Doherty George A GA

Journal of the American Chemical Society 20140718 30

A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid](+)[Co(CO)4](-) catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone. The success of this route to THL and its stereoisomers also demonstrated the practicality ...[more]

PMID: 25004122

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