Enantioselective Synthesis of the Ester Side Chain of Homoharringtonine

Abstract

Abstract Details of the synthesis of the methyl ester of the side chain of homoharringtonine, a natural product with antileukemic properties, are reported below. The key tactical element involved a Michael addition between the known chiral imine 4 and 2‐acetoxyacrylonitrile ( 5 ), furnishing the adduct (2 R ,1′ R )‐ 6 with a high degree of regio‐ and stereoselectivity. This adduct was then converted into the target compound ( R )‐ 2 by a linear sequence of ten chemical operations, in 6.0% overall yield. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)