Synthesis of β-Lactam Antibiotics

1. Front Matter

   Pages I-XI

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2. Industrial Synthesis of Semisynthetic Antibiotics

   • Alle Bruggink, Peter D. Roy

   Pages 12-54

3. Molecular Precision in the Chemistry of Cephalosporin type Antibiotics

   • B. Zwanenburg, G. J. Kemperman, J. Zhu, R. de Gelder, F. J. Dommerholt, G. T. M. Titulaer et al.

   Pages 56-101

4. Biocatalysts and Biocatalysis in the Synthesis of ß-Lactam Antibiotics

   • R. A. Sheldon, F. van Rantwijk, L. M. van Langen, M. A. Wegman, L. Cao, M. H. A. Janssen

   Pages 102-148

5. Process Technology and Process Integration in the Preparation of Penicillins

   • L. A. M. van der Wielen, M. Ottens, A. J. J. Straathof

   Pages 150-205

6. Biocatalytic production of semi-synthetic cephalosporins: process technology and integration

   • J. Tramper, H. H. Beeftink, A. E. M. Janssen, L. P. Ooijkaas, J. L. van Roon, M. Strubel et al.

   Pages 206-249

7. Engineering enzymes for the synthesis of semi-synthetic antibiotics

   • Wynand B. L. Alkema, Erik J. de Vries, Charles M. H. Hensgens, Jolanda J. Polderman-Tijmes, Bauke W. Dijkstra, Dick B. Janssen

   Pages 250-279

8. Modeling the metabolism of Penicillin-G formation

   • W. M. van Gulik, W. A. van Winden, J. J. Heijnen

   Pages 280-334

Penicillins and cephalosporins have a long history in combating bacterial infections. Despite new infectious diseases and occurring resistance, beta-lactam antibiotics will for many years to come continue to play a prominent role in our therapeutic arsenal. This book covers the industrial development of the chemical and biochemical processes used to manufacture these products, as well as looking ahead to possible future processes. The interplay between synthetic organic chemistry with the understanding and application of enzymes, modeling of fermentation processes and integration through (bio-) chemical process engineering is illustrated. In-depth scientific approaches to biocatalysis and biocatalyst development including enzyme kinetics, enzyme crystal studies and semi-rational enzyme mutations are also presented. Metabolic pathway analysis and modeling of fermentation process are treated as well as molecular precision in synthetic approaches to beta-lactams, their precursors and derivatives. Process technology studies including new reactor concepts, possible short-cut routes and improved down-stream-processing methods complete a broad view on the scope and limitations of the presently developed industrial processes including an intriguing insight into future process possibilities. This book represents an excellent case study on the transformation of traditional, stoïchiometric, organic synthesis and classical fermentations into modern (bio-) catalysis and biosynthesis based on insights in metabolic pathways and enzyme actions.

• catalysis
• chemistry
• crystal
• enzymes
• metabolism
• organic chemistry

• Life Sciences R&D, DSM Research, Geleen, The Netherlands

  Alle Bruggink

• Department of Organic Chemistry, Nijmegen University, Nijmegen, The Netherlands

  Alle Bruggink

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