Towards Biocatalytic Synthesis of β-Lactam Antibiotics

Advanced Synthesis & CatalysisVolume 343, Issue 6-7 p. 559-576 Review Towards Biocatalytic Synthesis of β-Lactam Antibiotics Margreth A. Wegman, Margreth A. Wegman Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this authorMichiel H. A. Janssen, Michiel H. A. Janssen Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this authorFred van Rantwijk, Fred van Rantwijk Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this authorRoger A. Sheldon, Roger A. Sheldon secretariat-ock@tnw.tudelft.nl Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this author Margreth A. Wegman, Margreth A. Wegman Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this authorMichiel H. A. Janssen, Michiel H. A. Janssen Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this authorFred van Rantwijk, Fred van Rantwijk Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this authorRoger A. Sheldon, Roger A. Sheldon secretariat-ock@tnw.tudelft.nl Laboratory of Organic Chemistry and Catalysis, Delft University of Technology, Julianalaan 136, 2628 BL Delft, The Netherlands, Fax: (+31) 15–278–1415Search for more papers by this author First published: 28 August 2001 https://doi.org/10.1002/1615-4169(200108)343:6/7<559::AID-ADSC559>3.0.CO;2-ZCitations: 150AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract This review describes the remarkable transition in the manufacture of β-lactam antibiotics, which is driven by the desire to reduce or eliminate the production of waste and the dependence on organic solvents. To this effect, traditional chemical procedures are gradually being replaced by biotransformations. The β-lactam antibiotics industry has led the way in the introduction of biocatalysis in the fine chemicals industry by replacing the chemical multi-step process for the penicillin nucleus 6-aminopenicillanic acid (6-APA) by an enzymatic one in the early 1990's. Recently, bioprocesses have been developed for the synthesis of the cephalosporin nucleus, 7-aminodeacetoxycephalosporanic acid (7-ADCA) from a penicillin precursor and will shortly be commercialized. Thirty years of research have now resulted in viable enzymatic procedures for coupling the β-lactam nuclei with D-phenylglycine side-chains. The necessary adaptations in the synthesis of the side-chain donors have likewise resulted in more efficient procedures. 1 Introduction 2 Semi-Synthetic β-Lactam Antibiotics: Industrial Production Prior to 1985 3 Biocatalytic Synthesis of β-Lactam Nuclei 3.1 6-Aminopenicillanic Acid 3.2 7-Aminodeacetoxycephalosporanic Acid 4 Biocatalytic Routes to Side-Chains 4.1 Synthesis of the Side-Chain Building Blocks 4.2 Synthesis of Activated Side-Chain Donors 5 Enzymatic Coupling of the Side-Chains to the β-Lactam Nuclei 5.1 Chemical Procedures 5.2 Enzymatic Coupling 5.3 Practical Procedures for Enzymatic Coupling6 Conclusion and Future Outlook Citing Literature Volume343, Issue6-7Special Issue: BiocatalysisAugust 2001Pages 559-576 RelatedInformation