BOOK
Green and Sustainable Medicinal Chemistry
Louise Summerton | Helen F Sneddon | Leonie C Jones | James H Clark
(2016)
Additional Information
Book Details
Abstract
Pharmaceutical manufacturing was one of the first industries to recognize the importance of green chemistry, with pioneering work including green chemistry metrics and alternative solvents and reagents. Today, other topical factors also have to be taken into consideration, such as rapidly depleting resources, high energy costs and new legislation. This book addresses current challenges in modern green chemical technologies and sustainability thinking. It encompasses a broad range of topics covered by the CHEM21 project – Europe’s largest public-private partnership project which aims to develop a toolbox of sustainable technologies for green chemical intermediate manufacture. Divided into two sections, the book first gives an overview of the key green chemistry tools, guidance and considerations aimed at developing greener processes, before moving on to look at cutting-edge synthetic methodologies. Featuring innovative research, this book is an invaluable reference for chemists across academia and industry wanting to further their knowledge and understanding of this important topic.
Leonie C Jones is the Green Chemistry Education and Training Associate at the Green Chemistry Centre of Excellence (GGCE), University of York, UK, where she works on developing a range of green chemistry training materials for the CHEM21 project including on-line resources.
Louise Summerton is the Training, Education and Networks Manager in the Green Chemistry Centre of Excellence (GGCE), University of York, UK, where she is leading on the creation of the CHEM21 Education and Training package to promote the uptake of green chemistry in the pharmaceutical industry.
Helen F Sneddon is a medicinal chemist as GlaxoSmithKline, UK, where she founded and leads the GSK Green Chemistry Performance Unit, which looks at improving the environmental sustainability of research and development, and the routes arising from it.
James H Clark is Professor of Chemistry at the University of York, Director of the Green Chemistry Centre of Excellence, and a Director of the Biorenewables Development Centre, UK. He has been at the forefront of green chemistry worldwide for nearly 20 years.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Cover | Cover | ||
| Contents | xliii | ||
| Chapter 1 Green and Sustainable Chemistry: An Introduction | 1 | ||
| 1.1 What is Green Chemistry? | 1 | ||
| 1.2 Drivers for Change | 3 | ||
| 1.2.1 Legislation | 3 | ||
| 1.2.2 Elemental Sustainability | 3 | ||
| 1.2.3 Renewable Resources | 4 | ||
| 1.3 Biomass as a Chemical Feedstock | 5 | ||
| 1.4 Major Initiatives Worldwide | 8 | ||
| 1.5 Summary | 9 | ||
| Acknowledgements | 10 | ||
| References | 10 | ||
| Chapter 2 Tools for Facilitating More Sustainable Medicinal Chemistry | 12 | ||
| 2.1 Introduction | 12 | ||
| 2.2 Solvent Selection Guides | 13 | ||
| 2.2.1 Solvent Guidance for Chromatography | 19 | ||
| 2.2.2 Solvent Guidance for Principal Component Analysis (PCA) Viewers | 20 | ||
| 2.2.3 Tools That can Minimise Reliance on Non-preferred Solvents | 20 | ||
| 2.3 Reagent Selection Guides | 22 | ||
| 2.4 Reagent and Solvent Selection—Substrate Specificity | 24 | ||
| 2.5 Future Opportunities | 26 | ||
| 2.6 Summary | 26 | ||
| References | 26 | ||
| Chapter 3 Renewable Solvent Selection in Medicinal Chemistry | 28 | ||
| 3.1 Sources of Bio-based Solvents | 28 | ||
| 3.2 Solvent Selection | 32 | ||
| 3.3 Solvent Polarity | 33 | ||
| 3.3.1 Solubility Parameters | 33 | ||
| 3.3.2 Computational Polarity Modelling | 34 | ||
| 3.3.3 Linear Solvation Energy Relationships | 35 | ||
| 3.4 Chapter Summary | 38 | ||
| References | 39 | ||
| Chapter 4 Beyond Mass-based Metrics: Evaluating the Greenness of Your Reaction | 41 | ||
| 4.1 Introduction | 41 | ||
| 4.2 Boundaries of Metrics Assessment | 42 | ||
| 4.3 Tracking Improvements | 42 | ||
| 4.4 Factors to Take into Consideration | 43 | ||
| 4.4.1 Efficiency | 46 | ||
| 4.4.2 Waste | 46 | ||
| 4.4.3 Solvents | 46 | ||
| 4.4.4 Catalyst/Enzyme | 47 | ||
| 4.4.5 Elemental Sustainability | 47 | ||
| 4.4.6 Energy | 47 | ||
| 4.4.7 Health and Safety | 48 | ||
| 4.4.8 Chemicals of Environmental Concern | 48 | ||
| 4.5 Wider Considerations | 49 | ||
| 4.5.1 Renewability | 49 | ||
| 4.5.2 Life Cycle Assessment | 49 | ||
| 4.6 CHEM21 Metrics Toolkit | 50 | ||
| 4.7 Conclusion | 51 | ||
| 4.8 Summary Points | 51 | ||
| References | 51 | ||
| Chapter 5 The Importance of Elemental Sustainability and Critical Element Recovery for the Pharmaceutical Industry | 54 | ||
| 5.1 Elemental Sustainability | 54 | ||
| 5.1.1 Why is Elemental Sustainability Important? | 54 | ||
| 5.1.2 What are Critical Elements? | 56 | ||
| 5.1.3 Importance to the Pharmaceutical Industry | 59 | ||
| 5.2 Chapter Summary | 60 | ||
| References | 61 | ||
| Chapter 6 Presence, Fate and Risks of Pharmaceuticals in the Environment | 63 | ||
| 6.1 Introduction | 63 | ||
| 6.2 Active Ingredients, Adjuvants, Metabolites and Transformation Products | 64 | ||
| 6.3 Introduction into the Environment | 66 | ||
| 6.4 Presence in the Environment | 66 | ||
| 6.5 Fate | 67 | ||
| 6.6 Risks and Risk Assessment | 68 | ||
| 6.7 Summary | 70 | ||
| References | 70 | ||
| Chapter 7 Benign by Design | 73 | ||
| 7.1 Introduction | 73 | ||
| 7.2 Inherently Safe | 74 | ||
| 7.3 'The End of the Pipe's End' | 74 | ||
| 7.4 Stability—a Question of Conditions | 75 | ||
| 7.5 Structure Matters—Benign by Design | 76 | ||
| 7.6 Summary | 80 | ||
| References | 80 | ||
| Chapter 8 From Discovery to Manufacturing: Some SustainabilityChallenges Presented by the Requirements of Medicine Development | 82 | ||
| 8.1 Introduction | 82 | ||
| 8.2 Drug Development | 83 | ||
| 8.3 Development of the API Commercial Route | 84 | ||
| 8.3.1 Discovery | 84 | ||
| 8.3.2 Ensuring Delivery to Proof of Concept | 86 | ||
| 8.3.3 From Proof of Concept to Manufacturing | 86 | ||
| 8.3.4 The 12 Principles of Green Chemistry | 87 | ||
| 8.4 Quality Assurance | 91 | ||
| 8.4.1 Control of Process-related Impurities | 91 | ||
| 8.4.2 Residual Solvents | 91 | ||
| 8.4.3 Residual Metals | 92 | ||
| 8.4.4 Transmissible Spongiform Encephalopathy | 93 | ||
| 8.4.5 Genotoxic Impurities | 93 | ||
| 8.4.6 Control of Polymorphic Form and Stability | 94 | ||
| 8.5 Quality by Design | 94 | ||
| 8.6 Compound Attrition | 96 | ||
| 8.7 Conclusions | 96 | ||
| Acknowledgements | 97 | ||
| References | 97 | ||
| Chapter 9 Medicinal Chemistry: How ''Green'' is Our Synthetic Tool Box? | 101 | ||
| 9.1 Introduction | 101 | ||
| 9.2 From Hit to Candidate in Drug Discovery | 102 | ||
| 9.3 Multiparameter Space of Drug Discovery | 103 | ||
| 9.4 Lead Optimization Phase in Drug Discovery | 103 | ||
| 9.5 Synthetic Tool Box and Reaction Analysis | 105 | ||
| 9.6 'Greenness' and Metrics | 105 | ||
| 9.7 Magic Triangle: Choice of Synthetic Path | 107 | ||
| 9.8 Application of Green Chemistry Metrics | 109 | ||
| 9.9 How to Decrease MI and Amount of Waste? | 111 | ||
| 9.10 Energy Consumption | 113 | ||
| 9.11 How ''Green'' is Our Synthetic Tool Box? | 113 | ||
| 9.12 Summary | 113 | ||
| References | 114 | ||
| Chapter 10 Design of Experiments (DoE) for Greener Medicinal Chemistry | 116 | ||
| 10.1 Introduction | 116 | ||
| 10.2 Why use DoE in Medicinal Chemistry? | 117 | ||
| 10.3 Design of Experiments Explained | 118 | ||
| 10.4 Practical Considerations | 121 | ||
| 10.5 A Case Study | 125 | ||
| 10.6 Summary | 126 | ||
| Acknowledgements | 126 | ||
| References | 127 | ||
| Chapter 11 Pd-catalysed Cross- couplings for the PharmaceuticalSector and a Move to Cutting-edge C–H Bond Functionalization: Is Palladium Simply Too Precious? | 129 | ||
| Summary | 137 | ||
| Financial Disclosure | 138 | ||
| References | 138 | ||
| Chapter 12 The Growing Impact of Continuous Flow Methods on the Twelve Principles of Green Chemistry | 140 | ||
| 12.1 Introduction | 140 | ||
| 12.2 Principle 1: Prevent Waste Instead of Treating it | 141 | ||
| 12.3 Principle 2: Design Atom- e.cient Methods | 142 | ||
| 12.4 Principle 3: Wherever Practicable, SyntheticMethodologies Should be Designed to Use andGenerate Substances That Possess Little or no Toxicity to Human Health and the Environment | 143 | ||
| 12.5 Principle 4: Design New Products That Preserve Functionality While Reducing Toxicity | 143 | ||
| 12.6 Principle 5: Minimise the Use of Auxiliary Reagents and Solvents | 144 | ||
| 12.7 Principle 6: Minimal Energy Requirements | 145 | ||
| 12.8 Principle 7: Renewable Raw Materials | 146 | ||
| 12.9 Principle 8: Avoid Unnecessary Derivatization | 148 | ||
| 12.10 Principle 9: Catalytic Reagents are Superior to Stoichiometric Reagents | 148 | ||
| 12.11 Principle 10: Design New Products With Biodegradable Capabilities | 150 | ||
| 12.12 Principle 11: Real-time and Online Process Analysis | 150 | ||
| 12.13 Principle 12: Substances should be chosen so asto Minimize the Potential for Chemical Accidents, Including Releases, Explosions and Fires | 151 | ||
| 12.14 Summary | 154 | ||
| References | 154 | ||
| Chapter 13 Green Catalytic Direct Amide Bond Formation | 156 | ||
| 13.1 Introduction | 156 | ||
| 13.2 Current Industrial Methods for Synthesizing Amide Bonds | 157 | ||
| 13.3 Research Trends: The Development of New Catalytic Systems | 159 | ||
| 13.4 Pros and Cons of New Catalytic Methods | 162 | ||
| 13.5 Application and Outlook for Catalytic Amidation in Pharmaceuticals and Fine Chemicals | 162 | ||
| 13.6 Conclusion | 163 | ||
| References | 163 | ||
| Chapter 14 Synthetic Biology for Organic Syntheses | 165 | ||
| 14.1 Synthetic Biology: A New Branch of Synthetic Chemistry? | 165 | ||
| 14.1.1 Synthetic Organic Chemistry Goes Green | 165 | ||
| 14.1.2 Biochemistry is Green per se inMany Aspects | 166 | ||
| 14.1.3 Synthetic Biology: Design and Synthesis of Biological Systems | 167 | ||
| 14.2 The Emerging Discipline of Synthetic Biology | 168 | ||
| 14.2.1 What Is Synthetic Biology? | 168 | ||
| 14.2.2 Parts, Devices and Systems: Basic Principles of Synthetic Biology | 168 | ||
| 14.3 Opportunities Synthetic Biology o.ers Green Chemistry | 170 | ||
| 14.3.1 Synthetic Biology in Service to Synthetic Chemistry? | 170 | ||
| 14.3.2 Opportunities for Synthetic Biology in Green Chemistry | 171 | ||
| 14.3.3 A Synthetic Biology Approach for the Biosynthesis of Artemisinin | 171 | ||
| 14.3.4 Vanillin Production in Yeasts | 173 | ||
| 14.4 Limitations of Synthetic Biology for Green Chemistry | 176 | ||
| 14.5 Summary | 178 | ||
| Acknowledgements | 178 | ||
| References | 178 | ||
| Chapter 15 Biocatalysis for Medicinal Chemistry | 180 | ||
| 1 Introduction to Recent Advances in Biocatalysis | 180 | ||
| 15.2 Some Enzyme Classes Readily Accessible to Medicinal Chemists | 183 | ||
| 15.2.1 Hydrolase Enzymes | 184 | ||
| 15.2.2 Ketone Reductases | 184 | ||
| 15.2.3 ω-Transaminase Enzymes\r | 185 | ||
| 15.2.4 Cytochrome P450s | 187 | ||
| 15.3 A Glimpse at Synthetic Biology and Pharmaceutical Synthesis | 188 | ||
| 15.4 Chapter Summary | 189 | ||
| References | 190 | ||
| Chapter 16 Base Metals in Catalysis: From Zero to Hero | 192 | ||
| 16.1 Base Metals: ''How Can We Serve You''? | 192 | ||
| 16.2 Base Metal Catalysis as a Sustainable Toolbox in Modern Chemistry: The Direct Amination Case | 196 | ||
| 16.3 Chapter Summary | 199 | ||
| References | 201 | ||
| Chapter 17 'Green' and Sustainable Halogenation Processes | 203 | ||
| 17.1 Introduction | 203 | ||
| 17.2 Electrophilic Fluorination | 204 | ||
| 17.3 Nucleophilic Fluorination | 208 | ||
| 17.4 C–H Fluorination | 211 | ||
| 17.5 Trifluoromethylation | 213 | ||
| 17.6 Other Halogenation Processes | 214 | ||
| 17.7 Summary | 216 | ||
| Acknowledgements | 216 | ||
| References | 216 | ||
| Subject Index | 218 |