Green Techniques for Organic Synthesis and Medicinal Chemistry

WEI ZHANG, PHD, is Professor of Chemistry and Director of the Center for Green Chemistry at the University of Massachusetts Boston. He is known for research work in organic synthesis, medicinal chemistry, and green chemistry. He received the 2015 International Fluorous Technology Award and is one of the top three most published authors in fluorous chemistry. BERKELEY W. CUE, PHD, is President and Founder of BWC Pharma Consulting LLC, a consultancy specializing in pharmaceutical sciences and green chemistry, and Adjunct Professor of Chemistry at the University of Massachusetts Boston.

• List of Contributors xviiForeword xxiPreface xxiiiPart I General Topics in Green Chemistry 11 Green Chemistry Metrics 3Frank Roschangar and Juan Colberg1.1 Business Case 31.2 Historical Context 31.3 Metrics, Awards, and Barriers 41.4 Metrics Unification Via Green Aspiration Level 91.5 Green Scorecard 121.6 Supply Chain 141.7 Outlook and Opportunities 15References 172 Green Solvents 21Janet L. Scott and Helen F. Sneddon2.1 Introduction 212.2 Solvent Selection Guides and Tools 232.3 Greener Molecular Solvents 242.4 Opportunities, Challenges, and Future Developments 34References 343 Green Analytical Chemistry 43Paul Ferguson and Douglas Raynie3.1 Introduction 433.2 Sample Preparation 473.3 Techniques and Methods 503.4 Process Analytical Technology 603.5 Biopharmaceutical Analysis 623.6 Conclusions 65Acknowledgments 66References 664 Green Engineering 71Christopher L. Kitchens and Lindsay Soh4.1 Introduction: Green Engineering Misconceptions and Realizations 714.2 12 Principles of Green Engineering 724.3 Green Chemistry Metrics Applied to Engineering 734.4 Use of Green Solvents in the Chemical Industry 804.5 Presidential Green Chemistry Awards 864.6 Opportunities and Outlook 87References 875 Greening of Consumer Cleaning Products 91David C. Long5.1 History of Green Consumer Cleaning Products 915.2 Drivers for Greener Products 945.3 Development of Green Cleaning Criteria and Eco-Labeling 985.4 Development of Greener Ingredients for Cleaners 1025.5 The Future of Green Cleaning 111Acknowledgments 112References 1126 Innovation with Non-Covalent Derivatization 117John C. Warner and Emily Stoler6.1 Introduction 1176.2 NCD Overview 1186.3 Pharmaceutical NCDs 1216.4 Environmental and Green Chemistry Benefits 123References 123Part II Green Catalysts 1317 Catalytic C-H Bond Cleavage for Heterocyclic Compounds 133Zhanxiang Liu and Yuhong Zhang7.1 Introduction 1337.2 Synthesis of Nitrogen Heterocycles 1337.3 Synthesis of Oxygen-Containing Heterocycles 1447.4 Synthesis of Sulfur-Containing Heterocycles 1487.5 Medium-Sized Heterocyclic Compounds 1507.6 Conclusion 152References 1528 Biocatalysis 161James Lalonde8.1 Introduction 1618.2 Enzymes for Biocatalysis 1628.3 Advances in Enzyme Engineering and Directed Evolution 1648.4 Biocatalytic Synthesis of Pharmaceuticals: Case Studies of Highly Efficient Pharmaceutical Syntheses 1658.5 Summary and Future Outlook 178References 1809 Practical Asymmetric Organocatalysis 185Wen-Zhao Zhang, Samik Nanda, and Sanzhong Luo9.1 Introduction 1859.2 Aminocatalysis 1859.3 BrønstedAcidCatalysis 1919.4 Brønsted Base Catalysis 1939.5 Hydrogen-Bonding Catalysis 1979.6 Phase-Transfer Catalysis 2029.7 Lewis Acid, Lewis Base, and N-Heterocyclic Carbene Catalysis 2049.8 Large-Scale Reaction (>100-Gram Reaction) 2079.9 Conclusion 209References 20910 Fluorous Catalysis 219LászlóT.MikaandIstván T. Horváth10.1 Introduction and the Principles of Fluorous Catalysis 21910.2 Ligands for Fluorous Transition Metal Catalysts 22410.3 Synthetic Application of Fluorous Catalysis 22510.4 Fluorous Organocatalysis 25610.5 Other Applications of Fluorous Catalysis 259References 25911 Solid-Supported Catalysis 269Sukanta Bhattacharyya and Basudeb Basu11.1 Introduction 26911.2 Immobilized Palladium Catalysts 27011.3 Immobilized Rhodium Catalysts 27611.4 Immobilized Ruthenium Catalysts 27911.5 Other Immobilized Catalysts 28411.6 Conclusions 286References 28712 Asymmetric Organocatalysis in Aqueous Media 291Kartick C. Bhowmick and Tanmoy Chanda12.1 Introduction 29112.2 Carbon-Carbon Bond-Formation Reactions 29212.3 Reactions Other than C-C Bond Formation 31312.4 Conclusion 314References 314Part III Green Synthetic Techniques 32513 Solvent-Free Synthesis 327Kendra Leahy Denlinger and James Mack13.1 Introduction 32713.2 Ball Milling 328References 33914 Ultrasonic Reactions 343Rodrigo Cella and Hélio A. Stefani14.1 Introduction 34314.2 How Does Cavitation Work? 34314.3 Aldol/Condensation Reactions 34514.4 1,4-Addition 35114.5 Heterocycles Synthesis 35314.6 Coupling Reactions 35614.7 Wittig Reaction 36114.8 Diels-Alder Reaction 36214.9 Miscellaneous 36514.10 Conclusions 366References 36615 Photochemical Synthesis 373Stefano Protti, Maurizio Fagnoni, and Angelo Albini15.1 Introduction 37315.2 Synthesis and Rearrangement of Open-Chain Compounds 37615.3 Synthesis of Three- and Four-Membered Rings 38215.4 Synthesis of Five-, Six- (and Larger)-Membered Rings 39115.5 Oxygenation and Oxidation 39815.6 Conclusions 400Acknowledgments 401References 40116 Pot Economy Synthesis 407Wenbin Yi, Xin Zeng, and Song Gao16.1 Introduction 40716.2 Multicomponent Reactions 40716.3 One-Pot and Multi-Step Reactions 41516.4 One-Pot Asymmetric Synthesis 42416.5 Outlook 434References 43417 Microwave-Assisted Organic Synthesis: Overview of Recent Applications 441Nandini Sharma, Upendra K. Sharma, and Erik V. Van der Eycken17.1 Introduction 44117.2 C-H Functionalization 44917.3 Insertion Reactions 45217.4 Reduction 45317.5 Synthesis of Peptides and Related Fine Chemicals 45517.6 Newer Developments 45917.7 Summary 461References 46118 Solid-Supported Synthesis 469Indrajeet J. Barve and Chung-Ming SunAbbreviations 46918.1 Introduction 47118.2 Techniques of Solid-Phase Supported Synthesis 47218.3 Solid-Phase Supported Heterocyclic Chemistry 47618.4 Solid-Supported Synthesis of Natural Products 48618.5 Solid-Supported Organometallic Chemistry 49118.6 Solid-Phase Synthesis of Peptides 49318.7 Solid-Phase Supported Stereoselective Synthesis 49418.8 Interdisciplinary Solid-Supported Synthesis 499References 50519 Light Fluorous Synthesis 509Wei Zhang19.1 Introduction 50919.2 “Heavy” Versus “Light” Fluorous Chemistry 50919.3 The Green Chemistry Aspects of Fluorous Synthesis 51019.4 Fluorous Techniques for Discovery Chemistry 51119.5 Conclusions 533References 533Part IV Green Techniques and Strategies in the Pharmaceutical Industry 53920 Ionic Liquids in Pharmaceutical Industry 541Julia L. Shamshina, Paula Berton, Hui Wang, Xiaosi Zhou, Gabriela Gurau, and Robin D. RogersAbbreviations 54120.1 Introduction 54320.2 Finding the Right Role for ILs in the Pharmaceutical Industry 54420.3 Conclusions and Prospects 567References 56821 Green Technologies and Approaches in the Manufacture of Biologics 579Sa V. Ho and Kristi L. Budzinski21.1 Introduction 57921.2 Characteristics of Biologics 58021.3 Manufacture of Therapeutic Biologics 58121.4 Environmental Metrics Development and Impact Analysis 58721.5 Some Future Directions 59221.6 Conclusions 594Acknowledgments 594References 59422 Benchmarking Green Chemistry Adoption by “Big Pharma” and Generics Manufacturers 601Vesela R. Veleva and Berkeley W. Cue22.1 Introduction 60122.2 Literature Review 60222.3 Pharmaceutical Industry Overview and Green Chemistry Drivers 60422.4 Benchmarking Industry Adoption of Green Chemistry 60722.5 Results and Discussion 61022.6 Conclusion 616References 61623 Green Process Chemistry in the Pharmaceutical Industry: Case Studies Update (2012–2016) 621Joseph M. Fortunak, Ji Zhang, Frederick E. Nytko III, and Tiffany N. Ellison23.1 Introduction 62123.2 Pharmaceutical Patents Driving Innovation 62223.3 A Caution About Drug Manufacturing Costs 62323.4 Process Evolution by Multiple Route Discovery Efforts—Dolutegravir 62423.5 The Impact of Competition on Process Evolution—Tenofovir Disoproxil Fumarate 62823.6 Simeprevir (Olysio/Sovriad) and Analogues: Chiral Phase-Transfer Catalyst-Promoted Optical Alpha-Amino Acid Synthesis: A Metal-free Process 63323.7 Vaniprevir (MK 7009), Simeprevir (TMC435), and Danoprevir: Ring-Closing Metathesis (RCM) for Macrocyclic Lactam Synthesis: Now a Commercial Reality 63523.8 Daclatasvir (BMS-790052, Daklinza), and Ledipasvir (GS-5885): Palladium Catalyzed Cross-Coupling for Greening a Process 63823.9 Sitagliptin (Januvia) and Ponatinib (Iclusig): Greening the Process by Telescoping Multiple Steps Together 63923.10 Febuxostat (Uloric): Greening the Process via Metal Catalyzed C-H Activation: A Prospect 64123.11 Conclusions 644References 64424 Greener Pharmaceutical Science Through Collaboration: The ACS GCI Pharmaceutical Roundtable 649Julie B. Manley and Michael E. Kopach24.1 Introduction 64924.2 Establishing Pre-Competitive Collaborations 65024.3 Informing and Influencing the Research Agenda 65424.4 Developing Tools 66124.5 Educating Leaders 66624.6 Collaborating Globally 66824.7 Future Opportunities 66924.8 Success Factors 671References 673Index 675