Enzymatic Acyl Transfer in Penicillin and Cephalosporin Chemistry

Abstract

Enzymatically catalyzed N-acylations of β-lactam compounds, like 6-aminopenicillanic acid (6-APA), by esters and amides have been attracting increasing attention in the last decade (1–3). While chemical introduction of multifunctional side chains like D-α-aminoacids requires the introduction and removal of protecting groups, the enzymatic route is direct. Other attractive features of this approach include the mild conditions which minimize the destruction of the labile β-lactam ring and, in a process like cephalexin production, the advantageous coupling of this reaction with the preceding enzymatic deprotection of the cephalosporin amino group (4). Potential advantages include the use of racemates in place of the expensive D-aminoacids. The mechanism of the reaction has a bearing on various practical issues, including the substrates and methods used for enzyme screening.