A two-step, one-pot enzymatic synthesis of cephalexin from D-phenylglycine nitrile

✍ Scribed by Margreth A. Wegman; Luuk M. van Langen; Fred van Rantwijk; Roger A. Sheldon

• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 113 KB
• Volume: 79
• Category: Article
• ISSN: 0006-3592
• DOI: 10.1002/bit.10278

✦ Synopsis

Abstract

A cascade of two enzymatic transformations is employed in a one‐pot synthesis of cephalexin. The nitrile hydratase (from R. rhodochrous MAWE)‐catalyzed hydration of D‐phenylglycine nitrile to the corresponding amide was combined with the penicillin G acylase (penicillin amidohydrolase, E.C. 3.5.1.11)‐catalyzed acylation of 7‐ADCA with the in situ–formed amide to afford a two‐step, one‐pot synthesis of cephalexin. D‐Phenylglycine nitrile appeared to have a remarkable selective inhibitory effect on the penicillin G acylase, resulting in a threefold increase in the synthesis/hydrolysis (S/H) ratio. 1,5‐Dihydroxynaphthalene, when added to the reaction mixture, cocrystallized with cephalexin. The resulting low cephalexin concentration prevented its chemical as well as enzymatic degradation; cephalexin was obtained at 79% yield with an S/H ratio of 7.7. © 2002 Wiley Periodicals, Inc. Biotechnol Bioeng 79: 356–361, 2002.