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Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the anti-leukemia alkaloid (-)-deoxyharringtonine.

ABSTRACT: Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is reported, involving novel synthetic methods and strategies that include (1) the strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro-pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core by alpha-(beta-lactone)carboxylic acid derivatives to access the biologically active cephalotaxus esters. These innovations should allow rapid access not only to other Cephalotaxus alkaloids but also to non-natural analogues of potential therapeutic utility.

SUBMITTER: Eckelbarger JD

PROVIDER: S-EPMC2610334 | biostudies-literature | 2006 Aug

REPOSITORIES: biostudies-literature

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Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the anti-leukemia alkaloid (-)-deoxyharringtonine.

Eckelbarger Joseph D JD Wilmot Jeremy T JT Gin David Y DY

Journal of the American Chemical Society 20060801 32

Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is reported, involving novel synthetic methods and strategies that include (1) the strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro-pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core by alpha-(beta-lactone)carboxy ...[more]

PMID: 16895394

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