Synthesis of optically active homocysteine from methionine and its use in preparing four stereoisomers of cystathionine

Abstract

In order to synthesize four stereoisomers of cystathionine (CYT), D- and L-homocysteines (D- and L-Hcy) were synthesized from methionine (Met) by a facile procedure. L-Met was reacted with dichloroacetic acid in concentrated hydrochloric acid under reflux to give (4S)-1,3-thiazane-2,4-dicarboxylic acid hydrochloride [(4S)-TDC• HCl]. L-Hcy was obtained by treatment of (4S)-TDC• HCl with hydroxylamine. D-Hcy was also synthesized from D-Met via (4R)-TDC• HCl intermediate. The obtained D- and L-Hcy were condensed with (R)- and (S)-2-amino-3-chloropropanoic acid hydrochlorides under alkaline conditions to give four stereoisomers of CYT. © 2002 Pharmaceutical Society of Japan.