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Total synthesis of the lycopodium alkaloid (+)-serratezomine A.

ABSTRACT: The first total synthesis of (+)-serratezomine A is described. Key aspects of the synthesis include (a) the first deployment of free-radical-mediated vinyl amination (an intramolecular alkyne aminostannation) in a complex target synthesis, (b) the use of a beta-stannyl enamine as the lynchpin for convergent assembly of the natural product backbone, (c) the use of an oxidative allylation promoted by cerium(IV) (CAN) to establish the all-carbon quaternary chiral center with the proper configuration, and (d) an intramolecular substitution reaction to form the sensitive bridging lactone. Overall, 15 steps (longest linear sequence) are required to prepare the natural product from a commercially available aldehyde, and assembly of the contiguous array of six stereocenters is accomplished with high stereocontrol.

SUBMITTER: Chandra A

PROVIDER: S-EPMC2677822 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Total synthesis of the lycopodium alkaloid (+)-serratezomine A.

Chandra Aroop A Pigza Julie A JA Han Jeong-Seok JS Mutnick Daniel D Johnston Jeffrey N JN

Journal of the American Chemical Society 20090301 10

The first total synthesis of (+)-serratezomine A is described. Key aspects of the synthesis include (a) the first deployment of free-radical-mediated vinyl amination (an intramolecular alkyne aminostannation) in a complex target synthesis, (b) the use of a beta-stannyl enamine as the lynchpin for convergent assembly of the natural product backbone, (c) the use of an oxidative allylation promoted by cerium(IV) (CAN) to establish the all-carbon quaternary chiral center with the proper configuratio ...[more]

PMID: 19236097

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