Stereo-divergent synthesis of L-threo- and L-erythro-[2,3-2H2]amino acids using optically active dioxopiperazine as a chiral template

Abstract

A stereo-divergent synthesis of L-threo- and L-erythro-[2,3-²H₂]amino acids from the same chiral auxiliary is described. Aldolization of N,N′-di(tert-butoxycarbonyl)dioxopiperazine 2, derived from L-valine, with various aldehydes followed by successive elaboration gives various 2,3-dehydroamino acid derivatives. Catalytic deuteriation of the derivatives then followed by acidic hydrolysis affords L-[2,3-²H₂]amino acids in good yields with high optical purities. It becomes clear that diastereoselective deuteriation for either the threo or the erythro isomer depends upon the protective groups on the nitrogen atoms in the dioxopiperazine ring.