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Rapid access to spirocyclic oxindole alkaloids: application of the asymmetric palladium-catalyzed [3 + 2] trimethylenemethane cycloaddition.

ABSTRACT: The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (?)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.

SUBMITTER: Trost BM

PROVIDER: S-EPMC3992010 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Rapid access to spirocyclic oxindole alkaloids: application of the asymmetric palladium-catalyzed [3 + 2] trimethylenemethane cycloaddition.

Trost Barry M BM Bringley Dustin A DA Zhang Ting T Cramer Nicolai N

Journal of the American Chemical Society 20131101 44

The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the ...[more]

PMID: 24083654

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