Enzyme-mediated synthesis of EEHP and EMHP,useful pharmaceutical intermediates of PPAR agonists

A new scaleable synthetic route to the title compounds has been developed. The reaction pathway is based on the α-chymotrypsin-catalysed hydrolysis of the racemic ethyl 2-ethoxy-3-(p-methoxyphenyl)propanoate or of the racemic ethyl 2-methoxy-3-(p-methoxyphenyl)propanoate to give the corresponding resolved (S)-esters with excellent ee. The acids were easily separated from the (S)-esters by a simple acid–base work-up. The overall yields of 1 and 2 were 16% and 17%, respectively.