Strain-release rearrangement of N-vinyl-2-arylaziridines. Total synthesis of the anti-leukemia alkaloid (-)-deoxyharringtonine.
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.
Eckelbarger
Joseph D
JD
Department of Chemistry, University of Illinois, Urbana, Illinois 61801, USA.
Wilmot
Jeremy T
JT
Gin
David Y
DY
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001388:Aziridines / Q000737:chemistry*; D006248:Harringtonines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000077863:Homoharringtonine; D015394:Molecular Structure
D000970:Antineoplastic Agents; D001388:Aziridines; D006248:Harringtonines; C043095:deoxyharringtonine; D000077863:Homoharringtonine