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Enantioselective Total Synthesis of (-)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy.

ABSTRACT: The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed through a regioselective aziridine ring opening.

SUBMITTER: Hicks EF

PROVIDER: S-EPMC10885145 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Enantioselective Total Synthesis of (-)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy.

Hicks Elliot F EF Inoue Kengo K Stoltz Brian M BM

Journal of the American Chemical Society 20240212 7

The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed ...[more]

PMID: 38346145

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