Lipase catalysed synthesis of diacyl hydrazines: an indirect method for kinetic resolution of chiral acids

The acylation of hydrazine, to afford the N,N'-diacyl derivatives, was cata lysed by a number of lipases. The rates of the first and second steps depen ded on the lipase and the type of solvent used. Water, up to 0.4 M, had no detrimental effect on the yield and complete conversion to the N,N'-diacyl derivative was accomplished with some lipases. The hydrazide of 2-(4-isobut ylphenyl)propanoic acid (ibuprofen), prepared by non-enzymatic reaction of ibuprofen methyl ester with hydrazine, acted as a nucleophile towards sever al Lipases that do not accept ibuprofen derivatives as the acyl donor, but the enantiomer differentiation was inefficient in most cases. The best resu lt was obtained with Pseudomonas lipoprotein lipase on EP 100 which formed the (R) enantiomer of the product (N-octanoyl-N'-2-(4-isobutylphenyl)propan oylhydrazine) with an enantiomeric ratio E of 26. (C) 2000 Elsevier Science B.V. All lights reserved.