Co-solvent enhancement of enantioselectivity in lipase-catalysed hydrolysis of racemic esters. A process for production of homochiral C-3 building blocks using lipase B from Candida antarctica

Abstract Lipase-catalysed hydrolysis of butanoates of 3-methoxy-1-(phenylmethoxy)-2-propanol and 3-chloro-1-(phenylmethoxy)-2-propanol with various lipases gave low enantioselectivity, E . By additon of water miscible organic cosolvents, in particular tert -butanol and acetone, the E -value was raised from 7 to 220 for the useful chloro derivative. This finding has led to proposal of a process for production of homochiral C-3 synthons such as both enantiomers of phenylmethyl glycidyl ether starting from racemic epichlorohydrin. NMR studies of lipase B from Candida antarctica show that the conformation most likely is not changed upon addition of up to 50% acetone. Nuclear Overhause effects were observed upon irradiation of the phenyl protons of the substrate only in the presence of enzyme thus indicating an interaction between the two.