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Total synthesis of (-)-kopsinine and ent-(+)-kopsinine.

ABSTRACT: The total synthesis of (-)-kopsinine and its unnatural enantiomer is detailed, enlisting a late-stage SmI2-mediated transannular free radical conjugate addition reaction for construction of the core bicyclo[2.2.2]octane ring system with strategic C21-C2 bond formation. Key to the approach is assemblage of the underlying skeleton by an intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole that provided the precursor C21 functionalized pentacyclic ring system 1 in a single step in which the C3 methyl ester found in the natural product served as a key 1,3,4-oxadiazole substituent, activating it for participation in the initiating Diels-Alder reaction and stabilizing the intermediate 1,3-dipole.

SUBMITTER: Lee K

PROVIDER: S-EPMC4461145 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Total synthesis of (-)-kopsinine and ent-(+)-kopsinine.

Lee Kiyoun K Boger Dale L DL

Tetrahedron 20150601 22

The total synthesis of (-)-kopsinine and its unnatural enantiomer is detailed, enlisting a late-stage SmI2-mediated transannular free radical conjugate addition reaction for construction of the core bicyclo[2.2.2]octane ring system with strategic C21-C2 bond formation. Key to the approach is assemblage of the underlying skeleton by an intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole that provided the precursor C21 functionalized pentacyclic ring system 1 i ...[more]

PMID: 26074629

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