ENANTIOSELECTIVE SYNTHESIS OF (2R,3S)-3-ALKYLMALIC ACIDS, COMPETENT SUBSTRATES FOR 3-ISOPROPYLMALATE DEHYDROGENASE

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 gamma,delta-unsaturated alpha-hydroxycarboxylic acids were oxidatively transformed into the desired (2R,3S)-3-alkylmalic acid derivatives.