Versatile Synthon for Chirally β-Deuterated L-Amino Acids and Synthesis of (3R)- and (3S)-[3-²H₁]-L-Serine

Abstract

A divergent and highly enantioselective synthetic methodology for producing chirally β-deuterated L-amino acids was developed. This method is based upon the chirality transcription approach, using diacetone-D-glucos-3-ulose (1) as a template, 3-C-[2-²H₁]-Ethenyl-3-O-(N-benzyl)methylthioformimidoyl-D-allo-derivatives (3b and 3c), which are easily accessible from 1, were subjected to halonium ion-assisted cyclization to afford highly diastereoselectively and efficiently versatile 5-membered cyclic carbamate synthons having a stereochemically defined deuterated halomethyl group (4c and 4d, respectively). Subsequent straightforward transformation of these synthons gave rise to (3R)- and (3S)-[3-2H₁]-L-serine. Further transformation of the crucial halomethyl group of 4a-c was also pursued to extend this methodology.