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

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. (C) 2003 Elsevier B.V. All rights reserved.