Enzymatic coupling using a mixture of side chain donors affords a greener process for ampicillin

Abstract

The penicillin acylase catalyzed synthesis of ampicillin, via acylation of 6-aminopenicillanic acid with D-phenylglycine amide, is accompanied by the formation of the hydrolysis product D-phenylglycine. The recycling of D-phenylglycine in the process viaD-phenylglycine methyl ester hydrochloric acid salt was investigated. The efficiency of a resulting innovative process, using both the amide and ester as donors, was compared with the process without recycling and that with recycling via the amide. Recycling via the ester, in a mixed donor coupling, resulted in the most economic process with respect to the use of chemicals and the production of waste.