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Categories: Organic Chemistry >> Bio >> Biocatalysis

Organic Synthesis with Enzymes in Non-Aqueous Media

Giacomo Carrea, Sergio Riva

Hardcover, 328 Pages
First Edition, 2008
ISBN: 3-527-31846-1


losing 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.

Editorial Review

Enzymes frequently offer unique selectivity in reactions with appropriate substrates. In addition to examples of enantioselective reactions, surprising chemoselectivity and regioselectivity have been reported in the transformations of multifunctional molecules. However, a disadvantage is that there are limitations to enzymes functioning in organic solvents, since both enzymes and their natural biological substrates are more water soluble than the molecules that come up in the everyday life of a chemist.

Several interesting techniques are available that permit enzymes to function in organic media with comparable activity and selectivity to that found under physiological conditions, and these are described in the first portion of the present book. To provide a basic foundation, explanations are provided for a number of effects that influence enzyme function. Although there is some overlap between the chapters, these fundamental principles definitely make worthwhile reading, and are accessible to advanced students even as expressed in the mathematical symbolic expressions that are employed in a few of the chapters. In the later portions as well, where a large number of reaction examples are encountered, there are some chapters with a large proportion of specific formulas that should appeal primarily to engineers. Thus, for example, biphasic transformations are described in detail using numerous mathematical formulas, also to the extent that they relate to industrial scale processes, while at the same time other chapters are limited to reactions from the current literature.

This monograph combines a commendable introduction with a multitude of examples of the reactions of important functional groups, as well as technical chapters that are quite good albeit heavily laden with formulas. All of these make the book attractive to anyone with an interest in enzymes, or who is looking for alternatives or concrete information concerning the scale-up of a reaction, or who needs tips on the use of enzymes.


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.


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.