Selectivity of penicillin G acylase towards phenylacetic acid derivatives in amide bond synthesis in toluene

Penicillin G acylase (PGA) accepts in toluene several analogues of phenylacetic acid as acyl donors. The 4-hydroxyphenylacetic group is preferentially accepted, and steric factors, such as the substitution at the aromatic ring or at the methylene group, cause a remarkable reduction in the initial rates. Results indicate that the selectivity follows a similar trend both in toluene and in aqueous media and that the synthetic potential of PGA can be fully exploited also in non-aqueous media with the consequent advantages, such as the absence of competitive hydrolytic reactions, higher solubility of phenylacetic derivatives and the possibility of working with equimolar amounts of reactants.