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Applied Biocatalysis. The Chemist's Enzyme Toolbox. Edition No. 1

  • ID: 5185766
  • Book
  • September 2020
  • 560 Pages
  • John Wiley and Sons Ltd

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.

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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

2 Survey of Current Commercial Enzyme and Bioprocess Service Providers 27

2.1 Commercial Enzyme Suppliers/Distributors 28

2.2 Bioprocess Service Providers 92

2.3 Chemical Transformations of Selected Commercially Available Enzymes 103

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

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

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

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

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

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

4.2 Asymmetric Biosynthesis of L-Phosphinothricin by Transaminase 168

4.3 Application of In Situ Product Crystallisation in the Amine Transaminase from Silicibacter pomeroyi-Catalysed Synthesis of (S)-1-(3-Methoxyphenyl)ethylamine 173

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

4.5 Amination of Sugars Using Transaminases 182

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

5 Other Carbon–Nitrogen Bond-Forming Biotransformations 193

5.1 Biocatalytic N-Acylation of Anilines in Aqueous Media 193

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

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

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

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

5.6 Asymmetric Reductive Amination of Ketones Catalysed by Amine Dehydrogenases 221

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

6 Carbon–Carbon Bond Formation or Cleavage 237

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

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

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

6.4 Biocatalytic Friedel–Crafts-Type C-Acylation 250

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

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

7 Reductive Methods 263

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

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

7.3 Lab-Scale Synthesis of Eslicarbazepine 267

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

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

8 Oxidative Methods 281

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

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

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

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

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

8.6 Biocatalytic Preparation of Vanillin Catalysed by Eugenol Oxidase 308

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

8.8 Enzymatic Synthesis of Pinene-Derived Lactones 319

8.9 Enzymatic Preparation of Halogenated Hydroxyquinolines 326

9 Hydrolytic and Dehydratase Enzymes 333

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

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

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

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

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

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

10 Glycosylation, Sulphation and Phosphorylation 363

10.1 Rutinosidase Synthesis of Glycosyl Esters of Aromatic Acids 363

10.2 Biocatalytic Synthesis of Kojibiose Using a Mutant Transglycosylase 369

10.3 Biocatalytic Synthesis of Nigerose Using a Mutant Transglycosylase 377

10.4 Easy Sulphation of Phenols by a Bacterial Arylsulphotransferase 381

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

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

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

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

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

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

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

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

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

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

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

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

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

12 Chemo-Enzymatic Cascades 475

12.1 Synergistic Nitroreductase/Vanadium Catalysis for Chemoselective Nitroreductions 475

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

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

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

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

13 Whole-Cell Procedures 509

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

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

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

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

Index 535

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John Whittall Runcorn Stylacats. Ltd, UK.

Peter W. Sutton GlaxoSmithKline R&D Ltd.
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