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.

• Authors: Joseph D Eckelbarger, Jeremy T Wilmot, David Y Gin
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 128 Issue 32 Pg. 10370-1 (Aug 16 2006) ISSN: 0002-7863 [Print] United States
• PMID: 16895394 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Aziridines
• Harringtonines
• deoxyharringtonine
• Homoharringtonine

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Aziridines (chemistry)
• Harringtonines (chemical synthesis, chemistry, pharmacology)
• Homoharringtonine
• Molecular Structure