Asymmetric Synthesis of Functionalized α-Amino Acid Derivatives via the γ-Pyrone Carbaldimine-Based Organocatalytic Mannich Reaction.

Abstract

A powerful synthetic strategy for the asymmetric synthesis of enantiomerically enriched γ-functionalized α-amino acid derivatives based on the highly stereoselective proline-catalyzed Mannich-type reaction of pre-prepared or in situ-generated γ-pyrone-derived aldimines with carbonyl compounds and subsequent transformations of multifunctional reaction products has been developed. A significant positive nonlinear effect was detected for the key organocatalytic reaction. The developed strategy was applied for facile gram-scale preparation of (S)-γ-oxonorvaline, used for site-specific modification of proteins, and both enantiomers of amycolatolide A recently isolated from the lichen-derived actinomycete Amycolatopsis sp. YIM 130923.