Pharmaceutical Biocatalysis-Chemoenzymatic Synthesis of Active Pharmaceutical Ingredients

863 Pages·2019·38.676 MB·\863

by  Peter Grunwald (Editor)

Jenny Stanford Series
on Biocatalysis
Volume 5
Pharmaceutical Biocatalysis
Chemoenzymatic Synthesis of Active
Pharmaceutical Ingredients
Peter Grunwald
edited by
Jenny Stanford Series
on Biocatalysis
Volume 5
Pharmaceutical Biocatalysis
Jenny Stanford Series on Biocatalysis
Series Editor
Peter Grunwald
Titles in the Series
Published Vol. 5
Pharmaceutical Biocatalysis:
Vol. 1 Chemoenzymatic Synthesis
Industrial Biocatalysis of Active Pharmaceutical
Peter Grunwald, ed. Ingredients
2015 Peter Grunwald, ed.
978-981-4463-88-1 (Hardcover) 2019
978-981-4463-89-8 (eBook) 978-981-4800-80-8 (Hardcover)
978-0-429-35311-6 (eBook)
Vol. 2
Handbook of Carbohydrate- Forthcoming
Modifying Biocatalysts
Peter Grunwald, ed. Vol. 6
2016
Pharmaceutical Biocatalysis:
978-981-4669-78-8 (Hardcover)
Biotransformations, Novel
978-981-4669-79-5 (eBook)
Therapeutics, Natural Sources,
and Degradation
Vol. 3
Peter Grunwald, ed.
Biocatalysis and
2020
Nanotechnology
Peter Grunwald, ed.
Vol. 7
2017
Agricultural Biocatalysis
978-981-4613-69-9 (Hardcover)
Peter Grunwald, ed.
978-1-315-19660-2 (eBook)
2022
Vol. 4
Vol. 8
Pharmaceutical Biocatalysis:
Biocatalysis for Sustainable
Fundamentals, Enzyme
Process Development
Inhibitors, and Enzymes in
Health and Diseases Peter Grunwald, ed.
Peter Grunwald, ed. 2023
2019
978-981-4800-61-7 (Hardcover)
978-0-429-29503-4 (eBook)
Jenny Stanford Series
on Biocatalysis
Volume 5
Pharmaceutical Biocatalysis
Chemoenzymatic Synthesis of Active
Pharmaceutical Ingredients
edited by
Peter Grunwald
Published by
Jenny Stanford Publishing Pte. Ltd.
Level 34, Centennial Tower
3 Temasek Avenue
Singapore 039190
Email: [email protected]
Web: www.jennystanford.com
British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library.
Pharmaceutical Biocatalysis: Chemoenzymatic Synthesis of Active
Pharmaceutical Ingredients
Copyright © 2020 Jenny Stanford Publishing Pte. Ltd.
All rights reserved. This book, or parts thereof, may not be reproduced in any
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For photocopying of material in this volume, please pay a copying fee
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ISBN 978-981-4800-80-8 (Hardcover)
ISBN 978-0-429-35311-6 (eBook)
Contents
Preface
1. Fut ure Strategies for Commercial Biocatalysis xi1x
Robert E. Speight and Karen T. Robins
1.1 Introduction 1
1.2 Cascades 4
1.2.1 Cell-Free Enzyme Cascades 4
1.2.2 Chemoenzymatic Cascades 11
1.3 Micro- and Nanoscale Process Design
Considerations 19
1.3.1 Nanoscale Compartmentalisation 20
1.3.2 Microfluidic Reactors 23
2. 1Sy.4n theCtoinc cAlupspiroona ches to Inhibitors of Isoprenoid 26
Biosynthesis 31
Pedro Merino, Loredana Maiuolo, Ignacio Delso, Vincenzo Algieri,
Antonio De Nino, and Tomas Tejero
2.1 Introduction 31
2.2 Bisphosphonates 36
2.2.1 Direct Method: Reaction of Carboxylic
Derivatives with Phosphorous Reagents 36
2.2.2 Indirect Method: Reaction of
Acylphosphonates with Dialkyl Phosphites 43
2.2.3 Michael Addition to Tetraethyl
Vinylidenebisphosphonate 48
2.2.4 Alkylation of Tetralkylbisphosphonate 52
2.2.5 Other Methods 55
vi Contents
2.3 Non-Bisphosphonate Derivative 56
3. 2U.s4i ng Cao Rneccluodminbgin Raenmt aMrkesta genomic Lipase for 68
Enantiomeric Separation of Pharmaceutically
Important Drug Intermediates 77
Rakesh Kumar, Uttam Chand Banerjee, and Jagdeep Kaur
3.1 Introduction 77
3.2 The Metagenomic Approach 78
3.3 Lipases as Biocatalysts 78
3.4 Use of Lipases in Drug Synthesis 79
3.5 Results 80
3.5.1 Metagenomic DNA Isolation and Purification 80
3.5.2 Cloning of Lipase (LipR1) Gene from Soil
Sample 80
3.5.3 Expression and Purification of the LipR1
Protein 80
3.5.4 Eff ect of Temperature 81
3.5.5 Effect of pH 83
3.5.6 Thermostability Studies 83
3.5.7 Effect of Different Additives on Lipase
Activity 83
3.5.8 Substrate Specificity 86
3.5.9 Kinetic Study of the Purified Lipase 87
3.5.10 Application of This Lipase for
Transesterification Reactions 87
3.6 Use of Ionic Liquids 94
3.6.1 Reaction with 1-INDANOL 95
3.6.2 Reaction with (RS)-3-Benzyloxy-1,2-
propanediol 96
3.6.3 Reaction with (RS)-α-Methyl-4 Pyridine
Methanol 96
3.6.4 Reaction with (RS)-α-(Trifluoromethyl)
Benzyl Alcohol 97
3.6.5 Reaction with 1-(1-Naphthyl) Ethanol 98
3.7 Summary 98
Contents vii
4. Biotechnological Production of Prenylated Xanthones
for Pharmaceutical Use 103
Mariam Gaid, Poonam Singh, Islam El-Awaad, Mohamed Nagia,
and Ludger Beerhues
4.1 Introduction 103
4.2 Biosynthesis of the Core Structure 107
4.3 Enzymatic Prenylation of Xanthone Scaffolds in
Nature 110
4.4 Limitations of Chemical Synthesis 113
4.5 Biotechnological Approaches for in vitro
Production of Xanthones 116
4.5.1 In vitro Cultures 116
4.5.2 Cascade Biocatalysis: Learning from
Nature 121
4.6 Pharmacological Potential: Effect of
Pharmacophores on Cytotoxic Activity of
Xanthones 125
4.6.1 Bioactivities of Chiral Derivatives of
Xanthones 131
5. 4C.h7e mCooennczylumsiaotnics Approaches towards (S)-Duloxetine 113443
Danish Shahzad, Muhammad Faisal, and Aamer Saeed
5.1 Introduction 143
S
5.2 Chemoenzymatic Approaches towards
( )-Duloxetine 147
S
5.3 Stereoselective Resolution Mediated Synthetic
S
Approaches towards ( )-Duloxetine 148
5.3.1 Synthesis of ( )-Duloxetine via
S
Immobilized/Mobilized Lipases 148
5.3.2 Modified Synthesis of ( )-Duloxetine
through Dynamic Kinetic Resolution (DKR) 154
S
5.4 Stereoselective Reduction Mediated Synthetic
S Candida
Approaches towards ( )-Duloxetine 156
viswanathii
5.4.1 Synthesis of ( )-Duloxetine via
156
viii Contents
S
Candida pseudotropicalis
5.4.2 Synthesis of ( )-Duloxetine through
Rhodotorula glutinis
157
S
5.4.3 Application of to
Saccharomyces cerevisiae
Synthesize ( )-Duloxetine 158
S
5.4.4 -Based Synthetic
S Candida
Approach for ( )-Duloxetine 159
tropicalis
5.4.5 ( )-Duloxetine Synthesis via
S
160
Aromatoleum aromaticum
5.4.6 Synthesis of ( )-Duloxetine by
S
Recombinant 161
Exiguobacterium
5.4.7 Construction of ( )-Duloxetine Entity via
S
Recombinant sp. F42 161
Chryseobacterium
5.4.8 Synthesis of ( )-Duloxetine through
S
Recombinant sp. CA49 162
Rhodosporidium toruloides
5.4.9 ( )-Duloxetine Synthesis via Recombinant
Candida
163
albicans S
5.4.10 Application of Recombinant
to Synthesize ( )-Duloxetine 164
S
5.5 Enantioselective Hydrocyanation Mediated
S Prunus
Approaches towards ( )-Duloxetine 165
armeniaca
5.5.1 Synthesis of ( )-Duloxetine via
165
6. S5y.6n theCsoins coluf sAinonti oxidants via Biocatalysis 116761
Salman Zafar
6.1 Introduction 171
6.2 What Are Antioxidants? 172
6.3 Mechanism of Action 172
6.4 Free-Radical Sources and Implications 173
6.5 Antioxidants from Biocatalysis 176
6.5.1 Pure Enzyme Technology 176
6.5.2 Whole-Cell Biotransformation 179
6.6 Conclusion 184
Contents ix
7. Biocatalysts: The Different Classes and Applications
for Synthesis of APIs 189
Peter Grunwald
7.1 Introduction 189
7.2 Classification of Biocatalysts 189
7.3 Biocatalysts: Some General Properties 192
7.4 Enzymes: Mechanisms and Applications 194
7.4.1 Biocatalysts for Redox Reactions:
Mechanisms 194
7.4.1.1 Applications 195
7.4.2 Transaminases: Mechanism and
Applications 201
7.4.3 Hydrolases: Mechanism and Applications 203
7.4.4 Lyases: Aldolases—Mechanism 206
7.4.4.1 Application in drug design 208
7.4.5 Hydroxinitrile Lyases 211
8. 7La.5c casCeo-nMceludsiiaotne d Synthesis of Novel Antibiotics and 213
Amino Acid Derivatives 219
Annett Mikolasch
8.1 Introduction 219
8.2 Laccases as Mediator for Organic Synthesis 220
8.3 Enzymatic Transformation of Antibiotics 232
8.3.1 Phenolic Oxidative Homodimerization 232
8.3.2 Phenolic Oxidative Heterodimerization 234
para
8.3.3 Oxidation Followed by Nuclear Amination 235
8.3.3.1 -Dihydroxy aromatic acids
and their derivatives aminated
ortho
by amino-β-lactams 235
8.3.3.2 -Dihydroxy aromatic acids
and their derivatives aminated
meta
by amino-β-lactams 243
8.3.3.3 -Dihydroxy aromatics and
their reactivity 246