Enantioselective Synthesis of (2R, 3S)-3-Alkylmalic Acids, Competent Substrates for 3-Isopropylmalate Dehydrogenase

Abstract

A series of (2R, 3S)-3-alkylmalic acids was enantioselectively synthesized, in conjunction with biochemical studies on the thermostable isopropylmalate dehydrogenase derived from Thermus thermophilus, by the chirality transcription approach, using a conceptually recyclable carbohydrate template. The dianion [2, 3]-Wittig rearrangement of alkylated allyloxyacetic acids prepared from alkylallyl tertiary-carbinols was effective in both reactivity and stereoselectivity to afford the desired diastereomers in a high yield. The derived γ, δ-unsaturated α-hydroxycarboxylic acids were oxidatively transformed into the desired (2R, 3S)-3-alkylmalic acid derivatives.