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Total synthesis of the cytotoxic cyclodepsipeptide (-)-doliculide: the "ester" effect in acyclic 1,3-induction of deoxypropionates.

ABSTRACT: The total synthesis of the marine cyclodepsipeptide (-)-doliculide is described. An acyclic (2S,4S,6R)-trimethyl alkanoic acid precursor to the "hydrocarbon" portion of doliculide was synthesized starting with l-ascorbic acid based on a stereocontrolled iterative conjugate addition of lithium dimethylcuprate to acyclic delta-Cmethyl alpha,beta-unsaturated ester derivatives. syn/syn selectivity was achieved by relying on 1,3-induction in preferred folded conformations that avoid 1,5-syn-pentane interactions in the transition states. The nature of the ester moiety seems to play an important role in determining the syn/anti ratios of C-methyl adducts. The 1-methyl-1-cyclopentyl ester group was found to confer the best syn selectivity to the cuprate addition products, especially in seven-carbon enoates.

SUBMITTER: Hanessian S

PROVIDER: S-EPMC514423 | biostudies-literature | 2004 Aug

REPOSITORIES: biostudies-literature

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Total synthesis of the cytotoxic cyclodepsipeptide (-)-doliculide: the "ester" effect in acyclic 1,3-induction of deoxypropionates.

Hanessian Stephen S Mascitti Vincent V Giroux Simon S

Proceedings of the National Academy of Sciences of the United States of America 20040621 33

The total synthesis of the marine cyclodepsipeptide (-)-doliculide is described. An acyclic (2S,4S,6R)-trimethyl alkanoic acid precursor to the "hydrocarbon" portion of doliculide was synthesized starting with l-ascorbic acid based on a stereocontrolled iterative conjugate addition of lithium dimethylcuprate to acyclic delta-Cmethyl alpha,beta-unsaturated ester derivatives. syn/syn selectivity was achieved by relying on 1,3-induction in preferred folded conformations that avoid 1,5-syn-pentane i ...[more]

PMID: 15210988

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