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A(1,3)-strain enabled retention of chirality during bis-cyclization of beta-ketoamides: total synthesis of (-)-salinosporamide A and (-)-homosalinosporamide A.

ABSTRACT: A concise, enantioselective synthesis of the Phase I anticancer agent, (-)-salinosporamide A, is described. The brevity of the described strategy stems from a key bis-cyclization of a beta-keto tertiary amide, accomplished on gram scale, which retains optical purity enabled by A(1,3)-strain rendering epimerization slow relative to the rate of bis-cyclization. The versatility of the strategy for derivative synthesis is demonstrated by the synthesis of (-)-homosalinosporamide A.

SUBMITTER: Nguyen H

PROVIDER: S-EPMC2981177 | biostudies-other | 2010 Jul

REPOSITORIES: biostudies-other

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A(1,3)-strain enabled retention of chirality during bis-cyclization of beta-ketoamides: total synthesis of (-)-salinosporamide A and (-)-homosalinosporamide A.

Nguyen Henry H Ma Gil G Romo Daniel D

Chemical communications (Cambridge, England) 20100525 26

A concise, enantioselective synthesis of the Phase I anticancer agent, (-)-salinosporamide A, is described. The brevity of the described strategy stems from a key bis-cyclization of a beta-keto tertiary amide, accomplished on gram scale, which retains optical purity enabled by A(1,3)-strain rendering epimerization slow relative to the rate of bis-cyclization. The versatility of the strategy for derivative synthesis is demonstrated by the synthesis of (-)-homosalinosporamide A. ...[more]

PMID: 20498903

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