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Total Synthesis of (-)-Mitrephorone A Enabled by Stereoselective Nitrile Oxide Cycloaddition and Tetrasubstituted Olefin Synthesis.

ABSTRACT: A highly enantioselective and diastereoselective total synthesis of the diterpenoid (-)-mitrephorone A is presented. Key to the synthesis are stereocontrolled 1,4-semihydrogenation of a 1,3-diene to a tetrasubstituted double bond, enzyme-catalyzed malonate desymmetrization, and highly diastereoselective nitrile oxide cycloaddition. The streamlined strategy is a considerable improvement to those reported earlier in terms of diastereo- and enantioselectivity. For the first time, the combination of modern Pd-cross-coupling with Cr-catalyzed reduction allows for rapid access to tetrasubstituted olefins with full stereocontrol.

SUBMITTER: Schneider M

PROVIDER: S-EPMC7564100 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Total Synthesis of (-)-Mitrephorone A Enabled by Stereoselective Nitrile Oxide Cycloaddition and Tetrasubstituted Olefin Synthesis.

Schneider Michael M Richter Matthieu J R MJR Carreira Erick M EM

Journal of the American Chemical Society 20201006 41

A highly enantioselective and diastereoselective total synthesis of the diterpenoid (-)-mitrephorone A is presented. Key to the synthesis are stereocontrolled 1,4-semihydrogenation of a 1,3-diene to a tetrasubstituted double bond, enzyme-catalyzed malonate desymmetrization, and highly diastereoselective nitrile oxide cycloaddition. The streamlined strategy is a considerable improvement to those reported earlier in terms of diastereo- and enantioselectivity. For the first time, the combination of ...[more]

PMID: 33021371

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