Strain-Release Rearrangement of N-Vinyl-2-Arylaziridines. Total Synthesis of the Anti-Leukemia Alkaloid (−)-Deoxyharringtonine

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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 α-(β-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.