Green Biocatalysis Green Biocatalysis Edited by Ramesh N. Patel NO PROTECTION CATALYTIC DEPROTECTION PROCESSES STEPS HIGH YIELDS, SELECTIVITY & SAFER & MILDER PRODUCT PURITY PROCESSES GREEN BIOCATALYTIC PROCESSES CATALYSTS WASTE REUSABILITY MINIMIZATION ATOM & ENERGY RENEWABLE EFFICIENT RESOURCE PROCESSES UTILIZATION Copyright © 2016 by John Wiley & Sons, Inc. 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Identifiers: LCCN 2015047535 (print) | LCCN 2015047720 (ebook) | ISBN 9781118822296 (hardback) | ISBN 9781118822357 (pdf) | ISBN 9781118822364 (epub) Subjects: LCSH: Enzymes–Biotechnology. | Biocatalysis. | Green chemistry. |BISAC: TECHNOLOGY & ENGINEERING / Chemical & Biochemical. Classification: LCC TP248.65.E59 G735 2016 (print) | LCC TP248.65.E59 (ebook) | DDC 660–dc23 LC record available at http://lccn.loc.gov/2015047535 Cover image courtesy of Wiley Set in 10/12pt Palatino by SPi Global, Pondicherry, India Printed in the United States of America 10 9 8 7 6 5 4 3 2 1 Contents Preface xix About the Editor xxiii Contributors xxv Chapter 1 Biocatalysis and Green Chemistry 1 Roger A. Sheldon 1.1 Introduction to Sustainable Development and Green Chemistry 1 1.2 Green Chemistry Metrics 2 1.3 Environmental Impact and Sustainability Metrics 4 1.4 Solvents 5 1.5 The Role of Catalysis 6 1.6 Biocatalysis and Green Chemistry 6 1.7 Examples of Green Biocatalytic Processes 8 1.7.1 A Chemoenzymatic Process for Pregabalin 8 1.7.2 A Three‐Enzyme Process for Atorvastatin Intermediate 8 1.7.3 Enzymatic Synthesis of Sitagliptin 11 1.7.4 Biocatalytic Synthesis of the Fragrance Chemical (−) Ambrox (Ambrafuran) 12 1.8 Conclusions and Future Prospects 13 References 13 Chapter 2 Enzymatic Synthesis of Chiral Amines using ω-Transaminases, Amine Oxidases, and the Berberine Bridge Enzyme 17 Eduardo Busto, Robert C. Simon, Nina Richter, and Wolfgang Kroutil 2.1 Introduction 17 2.2 Synthesis of Chiral Amines using ω‐Transaminases 18 2.2.1 ω‐Transaminases: Definition and General Facts 18 2.2.2 Stereoselective Transformations Involving ω‐TAs 18 2.2.3 Asymmetric Amination of Ketones 19 2.2.4 Asymmetric Amination of Linear Ketones 20 2.2.5 Asymmetric Amination of Cyclic Ketones 21 2.2.6 Application in the Synthesis of Pharmaceutically Active Ingredients 22 2.2.7 Amination of Ketones in Organic Solvents 24 2.2.8 Asymmetric Amination of Keto Acids: Synthesis of Nonnatural Amino Acids 25 2.2.9 Amination of Aldehydes 26 v vi Contents 2.2.10 Cascade Reactions Involving ω‐TAs 27 2.2.11 Cascades Initiated by ω‐TAs: Synthesis of Chiral Heterocycles 27 2.2.12 Multienzyme Cascades Involving ω‐TA‐Catalyzed Amination of Ketones 30 2.2.13 Deracemization of Primary Amines 32 2.2.14 Perspective 34 2.3 Amine Oxidases 34 2.3.1 Amino Acid Oxidases 35 2.3.2 Cascade Reactions Involving AAOs 38 2.3.3 Monoamine Oxidases 41 2.3.4 Cascade Reactions Involving Monoamine Oxidases 47 2.3.5 Perspective 49 2.4 Berberine Bridge Enzymes 50 2.5 Conclusions 52 References 53 Chapter 3 Decarboxylation and Racemization of Unnatural Compounds using Artificial Enzymes Derived from Arylmalonate Decarboxylase 59 Kenji Miyamoto 3.1 Introduction 59 3.2 Discovery of a Bacterial α‐Aryl‐α‐Methylmalonate Decarboxylase 61 3.3 Purification and Characterization of the Decarboxylase (AMDase) 61 3.4 Cloning of the AMDase Gene 62 3.5 Stereochemical Course of AMDase‐Catalyzed Decarboxylation 62 3.6 Directed Evolution of AMDase to an Artificial Profen Racemase 63 3.7 Inversion of Enantioselectivity Dramatically Improves Catalytic Activity 65 3.8 Future Prospects 68 References 69 Chapter 4 Green Processes for the Synthesis of Chiral Intermediates for the Development of Drugs 71 Ramesh N. Patel 4.1 Introduction 71 4.2 Saxagliptin: Enzymatic Synthesis of (S)‐N‐Boc‐3‐Hydroxyadamantylglycine 71 4.3 Sitagliptin: Enzymatic Synthesis of Chiral Amine 72 4.4 Vanlev: Enzymatic Synthesis of (S)‐6‐Hydroxynorleucine 73 4.5 Vanlev: Enzymatic Synthesis of Allysine Ethylene Acetal 74 4.6 Vanlev: Enzymatic Synthesis of Thiazepine 74 4.7 Tigemonam: Enzymatic Synthesis of (S)‐β‐Hydroxyvaline 76 4.8 Autoimmune Diseases: Enzymatic Synthesis of (S)‐Neopentylglycine 76 4.9 Atazanavir: Enzymatic Synthesis of (S)‐Tertiary Leucine 77 4.10 Thrombin Inhibitor (Inogatran): Synthesis of (R)‐Cyclohexylalanine 78 4.11 Gamma Secretase Inhibitor: Enzymatic Synthesis of (R)‐5,5,5‐Trifluoronorvaline 79 4.12 NK1/NK2 Dual Antagonists: Enzymatic Desymmetrization of Diethyl 3‐[3′,4′‐Dichlorophenyl] Glutarate 80 4.13 Pregabalin: Enzymatic Synthesis of Ethyl (S)‐3‐Cyano‐5‐Methylhexanoate 81 4.14 Chemokine Receptor Modulator: Enzymatic Synthesis of (1S,2R)‐2‐(Methoxycarbonyl)- Cyclohex‐4‐ene‐1‐Carboxylic Acid 82 Contents vii 4.15 Enzymatic Synthesis of (3S,5R)‐3‐(Aminomethyl)‐5‐Methyloctanoic Acid 82 4.16 Atorvastatin (Lipitor): Enzymatic Desymmetrization of 3‐Hydroxyglutaronitrile 83 4.17 Anticancer Drugs: Enzymatic Synthesis of Taxane Side Chain 84 4.18 Antidiabetic and CNS Drugs: Enzymatic Hydrolysis of Dimethyl Bicyclo[2.2.1] Heptane‐1,4‐Dicarboxylate 85 4.19 Clopidogrel (Plavix): Enzymatic Preparation of 2‐Chloromandelic Acid Esters 85 4.20 Antiviral Drug: Regioselective Enzymatic Acylation of Ribavirin 86 4.21 Anticholesterol Drug: Enzymatic Acylation of Alcohol 87 4.22 Saxagliptin: Enzymatic Synthesis of (5S)‐4,5‐Dihydro‐1H‐Pyrrole‐1,5 Dicarboxylic Acid, 1‐(1,1‐Dimethylethyl)‐5‐Ethyl Ester 88 4.23 Montelukast: Synthesis of Intermediate for LTD4 Antagonists 89 4.24 Atazanavir: Enzymatic Synthesis of (1S,2R)‐[3‐Chloro‐2‐Hydroxy‐1 (Phenylmethyl) Propyl]‐Carbamic Acid,1,1‐Dimethyl‐Ethyl Ester 90 4.25 Atorvastatin: Enzymatic Synthesis of (R)‐4‐Cyano‐3‐Hydroxybutyrate 91 4.26 Antianxiety Drug: Enzymatic Synthesis of 6‐Hydroxybuspirone 92 4.27 Protease Inhibitor: Enzymatic Synthesis of (R)‐3‐(4‐Fluorophenyl)‐2‐Hydroxy Propionic Acid 93 4.28 Dermatological and Anticancer Drugs: Enzymatic Synthesis of 2‐(R)‐Hydroxy‐2‐(1′,2′,3′, 4′‐Tetrahydro‐1′,1′,4′,4′‐Tetramethyl‐6′‐Naphthalenyl) Acetate 94 4.29 Antipsychotic Drug: Enzymatic Reduction of 1‐(4‐Fluorophenyl)4‐ [4‐(5‐Fluoro‐2‐Pyrimidinyl)1‐Piperazinyl]‐1‐Butanone 95 4.30 Cholesterol‐Lowering Agents: Enzymatic Synthesis of (3S,5R)‐Dihydroxy‐6‐(Benzyloxy) Hexanoic Acid, Ethyl Ester 95 4.31 Antimigraine Drugs: Enzymatic Synthesis of (R)‐2‐Amino‐3‐(7‐Methyl‐1H‐Indazol‐5‐yl) Propanoic Acid 96 4.32 Antidiabetic Drug (GLP‐1 Mimics): Enzymatic Synthesis of (S)‐Amino‐3‐[3‐{6‐(2‐ Methylphenyl)} Pyridyl]‐Propionic Acid 97 4.33 Ephedrine: Synthesis of (R)‐Phenylacetylcarbinol 98 4.34 Zanamivir: Enzymatic Synthesis of N‐Acetylneuraminic Acid 99 4.35 Epivir: Enzymatic Deamination Process for the Synthesis of (2′R‐cis)‐2′‐Deoxy‐3‐Thiacytidine 100 4.36 HMG‐CoA Reductase Inhibitors: Aldolase‐Catalyzed Synthesis of Chiral Lactol 101 4.37 Boceprevir: Oxidation of 6,6‐Dimethyl‐3‐Azabicyclo[3.1.0]Hexane by Monoamine Oxidase 102 4.38 Crixivan: Enzymatic Synthesis of Indandiols 103 4.39 Potassium Channel Opener: Preparation of Chiral Epoxide and trans‐Diol 104 4.40 Epothilones (Anticancer Drugs): Epothilone B and Epothilone F 105 4.41 β‐Adrenergic Blocking Agents: Synthesis of Intermediates for Propranolol and Denopamine 106 4.42 Conclusion 106 References 107 Chapter 5 Dynamic Kinetic Resolution of Alcohols, Amines, and Amino Acids 115 Jusuk Lee, Yoon Kyung Choi, Jaiwook Park, and Mahn‐Joo Kim 5.1 Introduction 115 5.1.1 Kinetic and Dynamic Kinetic Resolution 115 5.1.2 Enzymes as the Resolution Catalysts for DKR 115 5.1.3 The Enantioselectivity of Enzymes in DKR 116 5.1.4 Metal (Complexes) as the Racemization Catalysts for DKR 117 5.2 Dynamic Kinetic Resolution of Secondary Alcohols 119 5.3 Dynamic Kinetic Resolution of Amines and Amino Acids 133 5.4 Applications of Dynamic Kinetic Resolution 139 5.5 Summary 145 Appendix: List of Abbreviations 145 References 146 viii Contents Chapter 6 Recent Developments in Flavin-Based Catalysis: Enzymatic Sulfoxidation 149 Patricia B. Brondani, Marco W. Fraaije, and Gonzalo de Gonzalo 6.1 Introduction 149 6.2 Enzymatic Sulfoxidation Catalyzed by Flavoprotein Oxidases 150 6.3 Use of Flavoprotein Monooxygenases for the Synthesis of Chiral Sulfoxides 151 6.3.1 Sulfoxidations Catalyzed by Baeyer–Villiger Monooxygenases 152 6.3.2 Oxidative Processes Employing Styrene Monooxygenases 159 6.3.3 Enzymatic Sulfoxidations Catalyzed by Flavin‐Containing Monooxygenases 159 6.4 Asymmetric Sulfoxidation using Flavins as Catalysts 160 6.5 Summary and Outlook 162 References 163 Chapter 7 Development of Chemoenzymatic Processes: An Industrial Perspective 165 Rajesh Kumar, Carlos Martinez, Van Martin, and John Wong 7.1 Introduction 165 7.2 Synthetic Route Design and Integration of Biocatalysis 166 7.3 Screening and Biocatalyst Selection 169 7.4 Chemoenzymatic Process Development 169 7.4.1 Reaction Engineering versus Enzyme Engineering 169 7.4.2 Product Isolation 171 7.4.3 Scale‐Up of Enzymatic Processes 172 7.4.4 Enzyme Supply Scenarios 173 7.4.5 Manufacture of APIs using Enzymes: Quality and Safety Aspects 174 7.5 Conclusions 176 References 176 Chapter 8 Epoxide Hydrolases and their Application in Organic Synthesis 179 Alain Archelas, Gilles Iacazio, and Michael Kotik 8.1 Introduction 179 8.2 Sources and Reaction Mechanism of EHs 181 8.2.1 Sources of EHs 181 8.2.2 Heterologous Expression of EHs 182 8.2.3 Reaction Mechanisms of EHs 182 8.3 Directed Evolution and Genetic Engineering of EHs 183 8.4 Immobilized EHs and Reactions in Nonaqueous Media 186 8.4.1 Immobilization of EHs 186 8.4.2 EH‐Catalyzed Reactions in Organic Solvent‐ or Ionic Liquid‐Containing Media 188 8.5 Monofunctional Epoxides as Chiral Building Blocks for the Synthesis of Biologically Active Compounds 188 8.5.1 Monosubstituted Aromatic Epoxides 189 8.5.2 Disubstituted Aromatic Epoxides 194 8.5.3 Nonaromatic Epoxides 197 8.5.4 meso‐Epoxides 203 8.6 Preparation of Valuable Chiral Building Blocks for the Synthesis of Biologically Active Compounds Starting from Bifunctional Epoxides 204 8.6.1 Halogenated Epoxides 204 8.6.2 Epoxyamide 206 8.6.3 Protected Epoxy Alcohols 206