Facile Synthesis of (2R,3R)-Phenylalanine-2,3-d2 and NMR Study on Deuterated Gramicidin S

Abstract

Abstract (2R,3R)-Phenylalanine-2,3-d2 (d-Phe*) was synthesized through catalytic reduction of cyclo(-(Z)-2,3-dehydrophenylalanyl-d-alanyl-) under an atmosphere of 2H2 and successive acid hydrolysis in the yield of 80% in high chiral induction. The d-Phe* thus obtained was used for synthesis of [d-Phe*4,4′] gramicidin S (GS*). The 1H NMR spectrum of GS* in DMSO-d6 showed a sharp singlet at 2.98 ppm for the (3S)-proton of d-Phe* residue. It has been proposed that among rotamers of d-Phe aromatic side chain in GS the one with κ1=180° is predominant. The present observation provides sound evidence for assignments of d-Phe β-protons based on the proposal.