Applied Biocatalysis The Chemist's Enzyme Toolbox

by Whittall, John; Sutton, Peter W.

• ISBN13: 9781119487012
• ISBN10: 1119487013
• Edition: 1st
• Format: Hardcover
• Copyright: 2020-11-16
• Publisher: Wiley

Summary

Provides clear and comprehensive coverage of recently developed applied biocatalysis for synthetic organic chemists with an emphasis to promote green chemistry in pharmaceutical and process chemistry

This book aims to make biocatalysis more accessible to both academic and industrial synthetic organic chemists. It focuses on current topics within the applied industrial biocatalysis field and includes short but detailed experimental methods on timely novel biocatalytic transformations using new enzymes or new methodologies using known enzymes. The book also features reactions that are “expanding and making the enzyme toolbox available to chemists”—providing readers with comprehensive methodology and detailed key sourcing information of a wide range of enzymes.

Chapters in Applied Biocatalysis: The Chemist’s Enzyme Toolkit are organized by reaction type and feature a short introductory section describing the current state of the art for each example. Much of the book focuses on processes for which the enzymes are readily available so that organic chemists can synthesize appropriate quantities of chemicals with available materials in a standard chemical laboratory. Advanced methods are included to present examples of new enzymes that might encourage collaboration with suppliers or academic groups and that will educate chemists of rapidly expanding future possibilities.

• Focuses on current topics within the applied industrial biocatalysis field
• Offers experimental methods on novel biocatalytic transformations using new enzymes or new methodology using known enzymes
• Covers the hot topics of enzyme and chemoenzymatic cascades and biocatalysis in flow
• Edited by noted experts from both academia and industry with years of experience in the field of biocatalysis—particularly, the industrial applications of enzymes

Written for synthetic organic chemists working in all industries but especially the pharmaceutical industry and for those in academia with an eye for biocatalysis, Applied Biocatalysis: The Chemist’s Enzyme Toolkit will also benefit academic groups in chemistry and related sciences that are using enzymes for synthetic purposes, as well as those working in the area of enzymology and molecular biology.

Author Biography

John Whittall, PhD, works at the Centre of Excellence for Biocatalysis, Biotransformations and Biocatalytic Manufacture (CoEBio3), Manchester Institute of Biotechnology, University of Manchester, UK.

Peter W. Sutton, PhD, was Scientific Investigator, GlaxoSmithKline Research and Development Limited, UK, now R&D Director at GlycoScience S.L., Barcelona, Spain.

Table of Contents

Abbreviations xi

1 Directed Evolution of Enzymes Driving Innovation in API Manufacturing at GSK 1

1.1 Introduction 1

1.2 Drug Development Stages 3

1.3 Enzyme Panels 6

1.4 Enzyme Engineering 10

1.5 Case Studies 18

1.6 Outlook 22

Acknowledgements 23

References 23

2 Survey of Current Commercial Enzyme and Bioprocess Service Providers 27

Acknowledgements 133

References 133

3 Imine Reductases 135

3.1 Imine Reductase-Catalysed Enantioselective Reductive Amination for the Preparation of a Key Intermediate to Lysine-Specific Histone Demethylase 1 (LSD1) Inhibitor GSK2879552 135

References 138

3.2 Expanding the Collection of Immine Reductases Towards a Stereoselective Reductive Amination 138

References 143

3.3 Asymmetric Synthesis of the Key Intermediate of Dextromethorphan Catalysed by an Imine Reductase 143

References 148

3.4 Identification of Imine Reductases for Asymmetric Synthesis of 1-Aryl-Tetrahydroisoquinolines 148

Acknowledgements 155

References 155

3.5 Preparation of Imine Reductases at 15 L Scale and Their Application in Asymmetric Piperazine Synthesis 156

References 161

3.6 Screening of Imine Reductases and Scale-Up of an Oxidative Deamination of an Amine for Ketone Synthesis 162

4 Transaminases 165

4.1 A Practical Dynamic Kinetic Transamination for the Asymmetric Synthesis of the CGRP Receptor Antagonist Ubrogepant 165

References 167

4.2 Asymmetric Biosynthesis of L-Phosphinothricin by Transaminase 168

References 172

4.3 Application of In Situ Product Crystallisation in the Amine Transaminase from Silicibacter pomeroyi-Catalysed Synthesis of

(S)-1-(3-Methoxyphenyl)ethylamine 173

References 177

4.4 Enantioselective Synthesis of Industrially Relevant Amines Using an Immobilised ω-Transaminase 178

References 181

4.5 Amination of Sugars Using Transaminases 182

References 186

4.6 Converting Aldoses into Valuable ω-Amino Alcohols Using Amine Transaminases 187

References 190

5 Other Carbon–Nitrogen Bond-Forming Biotransformations 193

5.1 Biocatalytic N-Acylation of Anilines in Aqueous Media 193

References 195

5.2 Enantioselective Enzymatic Hydroaminations for the Production of Functionalised Aspartic Acids 196

References 203

5.3 Biocatalytic Asymmetric Aza-Michael Addition Reactions and Synthesis of L-Argininosuccinate by Argininosuccinate Lyase

ARG4-Catalysed Aza-Michael Addition of L-Arginine to Fumarate 204

References 210

5.4 Convenient Approach to the Biosynthesis of C2,C6-Disubstituted Purine Nucleosides Using E. coli Purine Nucleoside Phosphorylase and Arsenolysis 211

References 214

5.5 Production of L- and D-Phenylalanine Analogues Using Tailored Phenylalanine Ammonia-Lyases 215

References 220

5.6 Asymmetric Reductive Amination of Ketones Catalysed by Amine Dehydrogenases 221

References 230

5.7 Utilisation of Adenylating Enzymes for the Formation of N-Acyl Amides 231

References 236

6 Carbon–Carbon Bond Formation or Cleavage 237

6.1 Improved Enzymatic Method for the Synthesis of (R)-Phenylacetyl Carbinol 237

References 241

6.2 Tertiary Alcohol Formation Catalysed by a Rhamnulose-1-Phosphate Aldolase : Dendroketose-1-Phosphate Synthesis 241

References 246

6.3 Easy and Robust Synthesis of Substituted L-Tryptophans with Tryptophan Synthase from Salmonella enterica 247

References 250

6.4 Biocatalytic Friedel–Crafts-Type C-Acylation 250

References 255

6.5 MenD-Catalysed Synthesis of 6-Cyano-4-Oxohexanoic Acid 256

References 258

6.6 Production of (R)-2-(3,5-Dimethoxyphenyl)propanoic Acid Using an Aryl Malonate Decarboxylase from Bordetella bronchiseptica 259

References 261

7 Reductive Methods 263

7.1 Synthesis of Vibegron Enabled by a Ketoreductase Rationally Designed for High-pH Dynamic Kinetic Reduction 263

References 265

7.2 Synthesis of a GPR40 Partial Agonist Through a Kinetically Controlled Dynamic Enzymatic Ketone Reduction 265

References 267

7.3 Lab-Scale Synthesis of Eslicarbazepine 267

References 270

7.4 Direct Access to Aldehydes Using Commercially Available Carboxylic Acid Reductases 270

Acknowledgements 276

References 276

7.5 Preparation of Methyl (S)-3-Oxocyclohexanecarboxylate Using an Enoate Reductase 277

References 279

8 Oxidative Methods 281

8.1 Macrocyclic Baeyer–Villiger Monooxygenase Oxidation of Cyclopentadecanone on 1 L Scale 281

References 286

8.2 Regioselective Lactol Oxidation with O2 as Oxidant on 1 L Scale Using Alcohol Dehydrogenase and NAD(P)H Oxidase 286

References 291

8.3 Synthesis of (3R)-4-[2-Chloro-6-[[(R)-Methylsulphinyl]methyl]-Pyrimidin-4-yl]-3-Methyl-Morpholine Using BVMO-P1-D08 291

References 295

8.4 Oxidation of Vanillyl Alcohol to Vanillin with Molecular Oxygen Catalysed by Eugenol Oxidase on 1 L Scale 295

References 301

8.5 Synthesis of Syringaresinol from 2,6-Dimethoxy-4-Allylphenol Using an Oxidase/Peroxidase Enzyme System 301

References 307

8.6 Biocatalytic Preparation of Vanillin Catalysed by Eugenol Oxidase 308

References 311

8.7 Vanillyl Alcohol Oxidase-Catalysed Production of (R)-1-(4′-Hydroxyphenyl) Ethanol 312

References 319

8.8 Enzymatic Synthesis of Pinene-Derived Lactones 319

References 325

8.9 Enzymatic Preparation of Halogenated Hydroxyquinolines 326

References 331

9 Hydrolytic and Dehydratase Enzymes 333

9.1 Synthesis of (S)-3-(4-Chlorophenyl)-4-Cyanobutanoic Acid by a Mutant Nitrilase 333

References 337

9.2 Nitrilase-Mediated Synthesis of a Hydroxyphenylacetic Acid Substrate via a Cyanohydrin Intermediate 337

References 339

9.3 Production of (R)-2-Butyl-2-Ethyloxirane Using an Epoxide Hydrolase from Agromyces mediolanus 339

References 343

9.4 Preparation of (S)-1,2-Dodecanediol by Lipase-Catalysed Methanolysis of Racemic Bisbutyrate Followed by Selective Crystallisation 344

References 349

9.5 Biocatalytic Synthesis of n-Octanenitrile Using an Aldoxime Dehydratase from Bacillus sp. OxB-1 349

References 353

9.6 Access to (S)-4-Bromobutan-2-ol through Selective Dehalogenation of rac-1,3-Dibromobutane by Haloalkane Dehalogenase 354

Appendix 360

References 361

10 Glycosylation, Sulphation and Phosphorylation 363

10.1 Rutinosidase Synthesis of Glycosyl Esters of Aromatic Acids 363

References 368

10.2 Biocatalytic Synthesis of Kojibiose Using a Mutant Transglycosylase 369

References 376

10.3 Biocatalytic Synthesis of Nigerose Using a Mutant Transglycosylase 377

References 381

10.4 Easy Sulphation of Phenols by a Bacterial Arylsulphotransferase 381

References 386

10.5 Shikimate Kinase-Catalysed Phosphorylations and Synthesis of Shikimic Acid 3-Phosphate by AroL-Catalysed Phosphorylation of Shikimic Acid 386

References 393

10.6 Kinase-Catalysed Phosphorylations of Ketohexose Phosphates and LacC-Catalysed Synthesis of D-Tagatose 1,6-Diphosphate Lithium Salt 393

References 396

10.7 Kinase-Catalysed Phosphorylations of Xylulose Substrates and Synthesis of Xylulose-5-Phosphate Enantiomers 397

References 401

10.8 Phosphoramidates by Kinase-Catalysed Phosphorylation and Arginine Kinase-Catalysed Synthesis of Nω-Phospho-L-Arginine 401

References 407

11 Enzymatic Cascades 409

11.1 Redox-Neutral Ketoreductase and Imine Reductase Enzymatic Cascade for the Preparation of a Key Intermediate of the Lysine-Specific Histone Demethylase 1 (LSD1) Inhibitor GSK2879552 409

References 413

11.2 Asymmetric Synthesis of α-Amino Acids through Formal Enantioselective Biocatalytic Amination of Carboxylic Acids 413

References 420

11.3 Enantioselective, Catalytic One-Pot Synthesis of γ-Butyrolactone-Based Fragrances 420

References 426

11.4 Synthesis of Six out of Eight Carvo-Lactone Stereoisomers via a Novel Concurrent Redox Cascade Starting from (R)-and (S)-Carvones 426

References 434

11.5 One-Pot Biocatalytic Synthesis of D-Tryptophan Derivatives from Substituted Indoles and L-Serine 435

References 441

11.6 Escherichia coli Lysate Multienzyme Biocatalyst for the Synthesis of Uridine-5’-Triphosphate from Orotic Acid 4 and Ribose 1 441

References 449

11.7 Aerobic Synthesis of Aromatic Nitriles from Alcohols and Ammonia Using Galactose Oxidase 449

References 455

11.8 Hydrogen-Borrowing Conversion of Alcohols into Optically Active Primary Amines by Combination of Alcohol Dehydrogenases and Amine Dehydrogenases 455

References 468

11.9 Ene-Reductase-Mediated Reduction of C=C Double Bonds in the Presence of Conjugated C≡C Triple Bonds: Synthesis of (S)-2-Methyl-5-Phenylpent-4-Yn-1-Ol 468

References 474

12 Chemo-Enzymatic Cascades 475

12.1 Synergistic Nitroreductase/Vanadium Catalysis for Chemoselective Nitroreductions 475

References 481

12.2 Chemo-Enzymatic Synthesis of (S)-1,2,3,4-Tetrahydroisoquinoline Carboxylic Acids Using D-Amino Acid Oxidase 482

References 487

12.3 Amine Oxidase-Catalysed Deracemisation of (R,S)-4-Cl-Benzhydrylamine into the (R)-Enantiomer in the Presence of a Chemical Reductant 488

References 496

12.4 Asymmetric Synthesis of 1-Phenylpropan-2-Amine from Allylbenzene through a Sequential Strategy Involving a Wacker–Tsuji Oxidation and a Stereoselective Biotransamination 497

References 504

12.5 Chemoenzymatic Synthesis of (2S,3S)-2-Methylpyrrolidin-3-Ol 504

References 508

13 Whole-Cell Procedures 509

13.1 Semipreparative Biocatalytic Synthesis of (S)-1-Amino-1-(3’-Pyridyl)methylphosphonic Acid 509

References 514

13.2 Practical and User-Friendly Procedure for the Regio- and Stereoselective Hydration of Oleic, Linoleic and Linolenic Acids, Using Probiotic Lactobacillus Strains as Whole-Cell Biocatalysts 515

References 520

13.3 Clean Enzymatic Oxidation of 12α-Hydroxysteroids to 12-Oxo-Derivatives Catalysed by Hydroxysteroid Dehydrogenase 521

References 527

13.4 Whole-Cell Biocatalysis Using PmlABCDEF Monooxygenase and Its Mutants: A Versatile Toolkit for Selective Synthesis of Aromatic N-Oxides 528

References 533

Index 535