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Total synthesis of bryostatin 1.

ABSTRACT: Bryostatin 1 is a marine natural product that is a very promising lead compound because of the potent biological activity it displays against a variety of human disease states. We describe herein the first total synthesis of this agent. The synthetic route adopted is a highly convergent one in which the preformed, heavily functionalized pyran rings A and C are united by "pyran annulation", the TMSOTf-promoted reaction between a hydroxyallylsilane appended to the A-ring fragment and an aldehyde contained in the C-ring fragment, with concomitant formation of the B ring. Further elaborations of the resulting very highly functionalized intermediate include macrolactonization and selective cleavage of just one of five ester linkages present.

SUBMITTER: Keck GE

PROVIDER: S-EPMC3030632 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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Total synthesis of bryostatin 1.

Keck Gary E GE Poudel Yam B YB Cummins Thomas J TJ Rudra Arnab A Covel Jonathan A JA

Journal of the American Chemical Society 20101222 4

Bryostatin 1 is a marine natural product that is a very promising lead compound because of the potent biological activity it displays against a variety of human disease states. We describe herein the first total synthesis of this agent. The synthetic route adopted is a highly convergent one in which the preformed, heavily functionalized pyran rings A and C are united by "pyran annulation", the TMSOTf-promoted reaction between a hydroxyallylsilane appended to the A-ring fragment and an aldehyde c ...[more]

PMID: 21175177

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