Enzyme-catalysed optical resolution of mandelic acid via RS(∓)-methyl mandelate in non-aqueous media

Abstract

Separation of racemic mixtures is a formidable task and various approaches have been suggested. The resolution of R(−)-mandelic acid, which is used as an intermediate in pharmaceutical and drug industry, from a racemic mixture was studied in non-aqueous media via lipase catalyzed hydrolysis of RS(∓)-methyl mandelate. Novozym 435 (component B of the lipase from Candida antartica), lipozyme RM IM (Rhizomucor miehei lipase) and lipozyme TL IM (Thermomyces lanuginosus lipase) were screened for their activity and selectivity to get R(−)-mandelic acid. Novozym 435 was found to be the most effective in hydrolysis of R(−)-methyl mandelate with an optical purity of 78% at the end of 24 h. Effects of various process parameters such as speed of agitation, catalyst loading, substrate concentration, product concentration and temperature were studied. The ordered bi–bi mechanism with inhibition by both R(−)-methyl mandelate (substrate) and R(−)-mandelic acid (product) was found to fit the initial rate data very well and the kinetic constants were determined.