Synthesis of enantiopure α-deuteriated Boc-L-amino acids

Abstract

An alternative scheme for the synthesis of enantiopure α-deuteriated amino acids from a common intermediate is presented. Methyl bis(methylsulfanyl)methylene[2,2-²H₂]glycinate was prepared in a mixture of MeOD and D₂O with a catalytic amount of Na₂CO₃ and attached to (2R)-bornane-10,2-sultam. Alkylation of the corresponding enolate provided intermediates which after careful purification were first deprotected on nitrogen and then cleaved from the auxiliary to give deuteriated α-amino acids of very high purity ( > 99% ee and > 98% D). These were directly converted into the corresponding Boc-L-[2-²H]-Ala, -Leu, -Phe and -(O-Bzl)Tyr derivatives, suitable for application in peptide synthesis. Boc-[2,2-²H₂]Gly was also prepared.