Chemo-Enzymatic Cascade Reactions

A groundbreaking book focusing on chemo-enzymatic cascade transformations

Chemo-Enzymatic Cascade Reactions offers a unique book that explores biocatalytic-chemical cascade reactions and their applications in the synthesis of valuable chemicals. Written by a noted expert on the topic, this comprehensive resource includes information on the advantages and disadvantages of traditional chemical and biocatalytic reactions and reviews the three modes of chemo-enzymatic transformations: separate-pot-two-step, one-pot-two-step, and one-pot-one-step. The author examines the most current developments of chemo-enzymatic transformations organized by the three modes and types of enzymes and considers retro-synthesis based on both chemical and biocatalytic transformations and the synthetic applications.

This groundbreaking book is the first resource to present in one volume the state-of-art advances of the technology and explore the opportunities and challenges of this burgeoning field. The book also considers the future of cascade reactions and the myriad benefits including higher atom economy and production efficiency, and less resource consumption and waste generation. This important book:

Written for organic chemists, chemists in industry, biochemist, catalytic chemists, Chemo-Enzymatic Cascade Reactions offers an understanding to the importance, current advances, the opportunities and challenges of chemo-enzymatic synthetic technology.

Preface ix

1 Introduction 1

1.1 Advantages of Enzyme Catalysis 3

1.1.1 Chemoselectivity 3

1.1.2 Regioselectivity 4

1.1.3 Stereoselectivity 7

1.1.4 Mild Reaction Conditions 8

1.2 Modes of Chemoenzymatic Transformations 10

1.2.1 “Separate-Pot Two-Step” Mode 10

1.2.2 “One-Pot Two-Step” Mode 11

1.2.3 “One-Pot One-Step” Mode 12

References 14

2 “Separate-pot Two-step” Chemoenzymatic Transformation 19

2.1 Lipases 20

2.2 Nitrilases 31

2.3 Carbonyl Reductases 33

2.4 Ene Reductases 39

2.5 Transaminases 42

2.6 Imine Reductases 46

2.7 Cytochromes P450s 48

2.8 Baeyer–Villiger Monooxygenases (BVMOs) 56

2.9 Aldolases 59

2.10 Epoxide Hydrolases 64

2.11 Other Enzymes 67

2.12 Integration of Multienzyme Cascade with Chemical Transformation 74

2.13 Summary and Outlook 77

References 77

3 One-pot Sequential Chemoenzymatic Reactions 85

3.1 Lipases and Esterases 85

3.2 Carbonyl Reductases 94

3.3 Ene Reductases 113

3.4 Transaminases 114

3.5 Epoxide Hydrolases (EHs) 124

3.6 Other Enzymes 126

3.6.1 Aldolases 126

3.6.2 Halohydrin Dehalogenases 128

3.6.3 Phenylalanine Ammonia Lyases 129

3.6.4 D-Amino Acid Dehydrogenases (DAADHs) 131

3.6.5 Halogenases 132

3.6.6 Imine Reductases 134

3.6.7 Decarboxylases 135

3.6.8 Cytochrome P450s 136

3.6.9 Hydroxynitrile Lyases 137

3.6.10 Nitrilases 138

3.6.11 Laccases 138

3.6.12 Transglutaminases 139

3.6.13 α-Ketoglutarate (α-KG)-dependent Non-heme Iron Oxygenases 140

3.6.14 Galactose Oxidases 142

3.6.15 FAD-dependent Monooxygenases 143

3.7 Summary and Outlook 144

References 146

4 Chemoenzymatic Dynamic Kinetic Resolution 155

4.1 Enzymatic Kinetic Resolution 155

4.2 Dynamic Kinetic Resolution 156

4.3 Racemization Techniques 158

4.4 DKR of Chiral Alcohols 160

4.5 DKR of Chiral Amines 188

4.6 DKRs of Other Compounds 193

4.7 Summary and Outlook 204

References 205

5 Chemoenzymatic Concurrent Deracemization 217

5.1 Deracemization of Amino Acids and Amines 218

5.2 Deracemization of Hydroxy Acids and Alcohols 235

5.3 Deracemization of Chiral Sulfoxides 239

5.4 Summary and Outlook 239

References 240

6 One-pot Concurrent Chemoenzymatic Reactions 245

6.1 One-pot Concurrent Chemoenzymatic Cascades 247

6.1.1 Lipases 247

6.1.2 Carbonyl Reductases 267

6.1.3 Enoate Reductases 275

6.1.4 Transaminases 277

6.1.5 Monoamine Oxidases 279

6.1.6 Cytochrome P450s 284

6.1.7 Halohydrin Dehalogenases 286

6.1.8 Vanadium Haloperoxidases 287

6.1.9 Laccases 290

6.2 Integration of Chemical Reaction with Metabolism of Living Organisms 293

6.3 One-pot Concurrent Chemoenzymatic Cascades via Compartmentalization 297

6.4 Summary and Outlook 302

References 303

7 Photocatalytic and Biocatalytic Cascade Transformations 313

7.1 Photoenzymes 313

7.2 Light-Activation of Redox Enzymes Without Cofactor Regeneration 317

7.3 Light-Activated Cofactor Regeneration for Redox Enzymes 325

7.4 Photoinduced Catalytic Promiscuity of Redox Enzymes 330

7.5 Photocatalysis and Biocatalysis Cascades 335

7.6 Summary and Outlook 353

References 354

8 Perspectives 361

References 365

Index 369

Dunming Zhu, Ph.D., is a “Hundred Talents Program” Professor at Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, and Deputy Director of National Engineering Laboratory for Industrial Enzymes.