Lipase catalyzed regioselective hydrolysis of Crotepoxide isolated from Piper cubeb Cass DC

Regioselective hydrolysis of biologically active natural product crotepoxide (1), isolated from Piper cubeb Cass DC, has been studied employing various commercially available lipases. No conversions were observed with Aspergillus niger lipase (APL), Pseudomonas fluorescens lipase (PFL) and Lipase-M-Amano (LM). However, regioselective hydrolysis was achieved with Mucor miehei lipase (MML), Pseudomonas cepacia lipase (PSL), Candida cylindraceae lipase (CCL) and lipase from Porcine pancreas (PPL). The active enzymes were found to have distinct regioselectivity towards 1 with respect to hydrolysis of benzoyl and acetyl groups. While CCL was non-selective and hydrolysed both acetyl as well as benzoyl groups giving dideacetyl debenzoyl crotepoxide (4) as the only product, the reaction with PPL lead to formation of two products viz. 3-deacetyl crotepoxide (2) and 3-deacetyl-7-debenzoyl crotepoxide (3). MML catalysed reaction, though kinetically slow, afforded 3 as the only product while as PSL was successful in librating 7- and 3-hydroxyls, leaving 2-acetyl group intact, and showing 100% conversion of 1 to 3. This is the remarkable result as it can be employed to selectively liberate hydroxyl groups of 1 so as to make them available for selective derivatization even under mild conditions of neutral pH and room temperature without disturbing the epoxide rings.