Optical Resolution of (RS)-Mercaptosuccinic Acid and Syntheses of Four Stereoisomers of 2-Amino-3-[(1, 2-dicarboxyethyl)sulfanyl]propanoic Acid

Abstract

To synthesize four stereoisomers of 2-amino-3-[(1, 2-dicarboxyethyl)sulfanyl]propanoic acid (ADC), (RS)-mercaptosuccinic acid [(RS)-MSA] was optically resolved using (1S, 2S)-2-amino-1-phenyl-1, 3-propanediol and (R)- and (S)-1-phenylethylamine as resolving agents to yield (R)- and (S)-MSA with optical purities of 100%. In addition, the racemic structures of 1-propylammonium and 1-butylammonium salts of (RS)-MSA were examined based on melting point, solubility, infrared spectra, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-MSA. Results indicated that the 1-butylammonium salt of (RS)-MSA [(RS)-BA salt] exists as a conglomerate and that the 1-propylammonium salt forms a racemic compound. Optical resolution by preferential crystallization of (RS)-BA salt yielded (R)- and (S)-BA salts with optical purities of over 90%. The (R)- and (S)-MSA obtained by optical resolution were condensed with (R)- and (S)- 2-amino-3-chloropropanoic acid hydrochlorides to give (2R, 1'R)-, (2S, 1'S)-, (2R, 1'S)-, and (2S, 1'R)-ADC. In addition, these stereoisomers were also synthesized from D- and L-cysteine and optically active bromosuccinic acid.