Efficient and Scalable Asymmetric Total Synthesis of (−)-Emetine with Pharmaceutical Grade Quality; First Multigram Scale Synthesis

Abstract

A scalable asymmetric total synthesis of (−)-emetine, a natural product alkaloid from ipecac species and one of the main active ingredients in ipecac syrup used in emetics, has been accomplished. The synthetic route featured a total of 13 steps of highly efficient chemical reactions, including catalytic asymmetric allylation and an industrial deoxygenation of an aliphatic compound, which obviated the need for any chromatographic purification. (−)-Emetine·2HCl was obtained in 12% overall yield and over 93.2% HPLC purity. The synthesis was easily scaled up to 237.1 g and should be amenable to the production of larger quantities for ongoing drug development, while the compound is currently provided as natural ipecac syrup for a clinical use.