Selective Lipase-Catalysed Hydrolysis of a 1,2-Diester in the Development of a New Route to AZD2563 DSP

Abstract

During the development of a new route to AZD2563 DSP (DSP ) disodium phosphate), a selective enzyme-catalysed hydrolysis of a 1,2-diester moiety to produce the secondary monoester was developed. Apart from two esters, the target molecule also contained three further functional groups prone to hydrolysis. A major challenge to the chosen approach was the very facile rearrangement of the desired secondary monoester product to the undesired primary monoester. This rearrangement was found to be catalysed by a wide range of chemicals and inorganic materials usually considered as inert. The unique selectivity and mild operating conditions of biocatalysis allowed the desired reaction to be developed and successfully scaled up.

Lipase-Catalyzed One-Step and Regioselective Synthesis of Clindamycin Palmitate

“…This results in a yield being lower than 50% and produces various wastes and byproducts which impose a heavy burden onto the downstream processing . Lipase has been reported to catalyze esterification reactions with high regioselectivity, and thus holds promise for the synthesis of clindamycin palmitate. Here, we describe the first effort towards one-step synthesis of clindamycin palmitate by an enzymatic regioselective acylation of clindamycin with vinyl palmitate (Scheme ).…”