Synthesis of enantiomerically pure (R)- and (S)-2-sulfanylpropanoic acids (‘thiolactic acid’) from ethyl (S)-lactate using pig liver esterase

Abstract

The methanesulfonates of optically pure ethyl (S)-lactate or ethyl (R)-2-chloropropanoate 5, obtained with inversion of configuration from ethyl (S)-lactate on treatment with SOCl₂, can be substituted by caesium thiolates with inversion of configuration to yield (R) and (S) ethyl 2-(acetylsulfanyl)propanoate, 2a and 2b, respectively. Hydrolysis of the carboxy ester of 2a, 2b to the acid under common acidic or basic conditions always leads to substantial racemisation. However, the use of the mild biocatalyst pig liver esterase (PLE) at neutral pH yields the carboxylic acids 4a and 4b without racemisation. The acetylsulfanyl group remains unaffected during this process. Subsequent treatment of the acetylsulfanyl group of 4a or 4b with 2 mol dm^–3 aqueous ammonia leads to the useful optically pure building block (R)- or (S)-2-sulfanylpropanoic acid (‘thiolactic acid’)3a, 3b in an overall yield of 65% based on cheap ethyl (S)-lactate.