Organic Synthesis with Enzymes in Non-Aqueous Media »

Dr. Giacomo Carrea joined the Italian National Research Council (CNR) in 1969 where presently he is Director of the Institute of Chemistry of Molecular Recognition. He has been working in such fields as enzyme catalysis in organic solvents, synthesis of fine chemicals catalyzed by hydrolases, dehydrogenases, peroxidases and monooxygenases, study of conformation of proteins and polypeptides and analytical applications of bioluminescent enzymes. He is a member of the Editorial Board of "Trends in Biotechnology" and "Biocatalysis and Biotransformation" and the author of about 220 publications in international peer reviewed journals.

Dr. Sergio Riva is a Senior Research Scientist at the Institute of the Chemistry of Molecular Recognition. He took his Laurea in Chemistry in 1983 and his Diploma di Specialita in Organic Synthesis in 1989. In 1987 he was at M.I.T. (USA) working with Prof. A. Klibanov. In 1993 he was awarded the Ciamician medal by the Organic Chemical Division of the Italian Chemical Society for his research activity in biocatalysis, presently documented by more than 150 publications reporting on the isolation and characterization of enzymes and on the synthetic exploitation of these biocatalysts.

Closing a gap in the literature, this comprehensive book examines and discusses different non-aqueous systems from organic solvents to ionic liquids for synthetic applications, thus opening the door to new successful methods for biocatalytic reactions. It gathers into one handy source the information otherwise widely spread throughout the literature, combining useful background information with a number of synthetic examples, including industrial scale processes for pharmaceutical and fine chemicals.

Extremely well structured, the text introduces the fundamentals of non-aqueous enzymology, before going on to new reaction media and synthetic applications using hydrolases and non-hydrolytic enzymes.

The one-stop reference for everyone working in this hot field.

Preface.

List of Contributors.

Part One Biocatalysis in Neat Organic Solvents – Fundamentals.

1 Fundamentals of Biocatalysis in Neat Organic Solvents (Patrick Adlercreutz).

1.1 Introduction.

1.2 Effects of Water on Biocatalytic Reactions.

1.3 Solvent Effects.

1.4 Effects on Equilibria.

1.5 Effects of pH in Organic Solvents.

1.6 Concluding Remarks.

2 Effects of Organic Solvents on Enzyme Selectivity (Jaap A. Jongejan).

2.1 Introduction.

2.2 Enzyme Enantioselectivity.

2.3 Effects of Organic Solvents on the E-value.

2.4 Possible Causes of the Complexity of Solvent Effects on E.

2.5 The Accuracy of E-value Determinations.

2.6 Kinetic and Thermodynamic Analysis of the Specifi city Constants.

2.7 Solvents Effects on Non-Hydrolytic Enzymes.

2.8 Major Achievements.

2.9 Concluding Remarks.

3 Activating Enzymes for Use in Organic Solvents (Anne L. Serdakowski, Jonathan S. Dordick).

3.1 Introduction.

3.2 Water – A Unique and Necessary Solvent for Enzymatic Catalysis.

3.3 Enzyme Activation in Nonaqueous Media.

3.4 Salt-Activated Enzymes.

3.5 Conclusions.

Part Two Biocatalysis in Neat Organic Solvents – Synthetic Applications 4 Exploiting Enantioselectivity of Hydrolases in Organic Solvents (Hans-Erik Högberg).

4.1 Introduction.

4.2 Enantioselective Reactions in Organic Solvents.

4.3 Summary and Outlook.

5 Chemoenzymatic Deracemization Processes (Belén Martín-Matute and Jan-E. Bäckvall).

5.1 Introduction.

5.2 Dynamic Kinetic Resolution.

5.3 Cyclic Deracemizations.

5.4 Concluding Remarks.

6 Exploiting Enzyme Chemoselectivity and Regioselectivity (Sergio Riva).

6.1 Introduction.

6.2 Chemoselectivity of Hydrolases.

6.3 Regioselectivity of Hydrolases.

6.4 Closing remarks.

7 Industrial-Scale Applications of Enzymes in Non-Aqueous Solvents (David Pollard and Birgit Kosjek).

7.1 Introduction.

7.2 Ester Synthesis by Esterifi cation.

7.3 Resolution of Racemic Alcohols.

7.4 Kinetic Resolution of Racemic Amines.

7.5 Resolution of Amino Alcohols and Methyl Ethers.

7.6 Resolution of an Ester.

7.7 Desymmetrization by Transesterifi cation.

7.8 Regioselective Acylation.

7.9 Asymmetric Ring Opening of Racemic Azlactone.

7.10 Cyanohydrin Formation.

7.11 Outlook.

Part Three Biocatalysis in Biphasic and New Reaction Media.

8 Biocatalysis in Biphasic Systems: General (Pedro Fernandes and Joaquim M. S. Cabral).

8.1 Introduction.

8.2 Organic-Aqueous Biphasic Systems: General Considerations.

8.3 Classifi cation of the Systems: Macro- and Microheterogeneous Systems.

8.4 Mechanisms of Enzyme Inactivation.

8.5 Approaches to Protection of the Enzyme.

8.6 Solvent Selection.

8.7 Operational Parameters.

8.8 Reactor Types.

8.9 Downstream Processing.

8.10 Recent Applications.

8.11 Conclusions.

Acknowledgments.

9 Biocatalysis in Biphasic Systems: Oxynitrilases (Manuela Avi and Herfried Griengl).

9.1 Introduction.

9.2 Biphasic Systems.

9.3 Conclusion.

10 Ionic Liquids as Media for Enzymatic Transformations (Roger A. Sheldon and Fred van Rantwijk).

10.1 Introduction.

10.2 Solvent Properties of Ionic Liquids.

10.3 Enzymes in Ionic Liquids.

10.4 Enzymes in Nearly Anhydrous Ionic Liquids.

10.5 Stability of Enzymes in Nearly Anhydrous Ionic Liquids.

10.6 Whole-Cell Biotransformations in Ionic Liquids.

10.7 Biotransformations in Ionic Liquid Media.

10.8 Downstream Processing.

10.9 Conclusions.

11 Solid/Gas Biocatalysis (Isabelle Goubet, Marianne Graber, Sylvain Lamare, Thierry Maugard and Marie-Dominique Legoy).

11.1 Introduction.

11.2 Operating Solid/Gas Systems.

11.3 Infl uence of Operational Parameters on the Dehalogenase Activity of Whole Dehydrated Cells.

11.4 Conclusion.

12 Biocatalysis with Undissolved Solid Substrates and Products (Alessandra Basso, Sara Cantone, Cynthia Ebert, Peter J. Halling and Lucia Gardossi).

12.1 Introduction.

12.2 The Reaction System: Classifi cation.

12.3 Theory.

12.4 Factors Affecting the Reactions in the Presence of Undissolved Substrates/Products.

12.5 Precipitation-Driven Synthesis of Peptides.

12.6 Precipitation-Driven Synthesis of Esters and Surfactants.

12.7 The Synthesis of β-Lactam Antibiotics in the Presence of Undissolved Substrates.

12.8 Conclusion.

Index.