Contents. Foreword V List of Contributors XV

Transcription

1 VII Contents Foreword V List of Contributors XV 1 Introduction to Green Chemistry, Organic Synthesis and Pharmaceuticals 1 Roger Sheldon 1.1 The Development of Organic Synthesis The Environmental Factor The Role of Catalysis Green Chemistry: Benign by Design Ibuprofen Manufacture The Question of Solvents: Alternative Reaction Media Biocatalysis: Green Chemistry Meets White Biotechnology Conclusions and Prospects 18 References 18 2 Green Chemistry Metrics 21 Richard K. Henderson, David J.C. Constable, and Concepción Jiménez-González 2.1 Introduction Measuring Resource Usage Focus on Solvents Focus on Renewables Cleaning and Maintenance Life Cycle Assessment (LCA) Measuring Chemistry and Process Efficiency Measuring Process Parameters and Emissions Real Time Analysis Scalability Controllability Robustness 38 Green Chemistry in the Pharmaceutical Industry. Edited by Peter J. Dunn, Andrew S. Wells and Michael T. Williams 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN:

2 VIII Contents 2.7 Operational Efficiency Measuring Energy Measuring the Toxicity of All the Substrates Occupational Exposure Hazard and Risk Measuring Degradation Potential Measuring the Inherent Safety or Lack of Inherent Safety Conclusions 45 References 46 3 Solvent Use and Waste Issues 49 C. Stewart Slater, Mariano J. Savelski, William A. Carole, and David J.C. Constable 3.1 Introduction to Solvent Use and Waste Issues Introduction Process Efficiency Metrics Impact Beyond the Plant Solvent Life Cycle Solvent Utilization Solvents Used in the Pharmaceutical Industry Solvent Use in Process Development Consequences of Excessive Solvent Use Waste Management Practices in the United States Solvent and Process Greenness Scoring and Selection Tools Review of Solvent and Process Scoring Methods Greenness Assessment of Pharmaceutical Processes and Technology Greenness Scoring Methods for Solvents The GSK Solvent Selection Guide The Rowan Solvent Greenness Index Method Waste Minimization and Solvent Recovery Minimizing Solvent Use Batch versus Continuous Reactors Biosynthetic Processes Solid-State Chemistry Telescoping Recycling Solvents Methods to Recover and Reuse Solvents Issues with Solvent Recovery and Reuse 79 Acknowledgments 80 References 81 4 Environmental and Regulatory Aspects 83 David Taylor and Vyvyan T. Coombe 4.1 Historical Perspective Pharmaceuticals in the Environment Presence Persistence Bioaccumulation 86

3 Contents IX Ecotoxicology The Current State of the Science Environmental Regulations Product Regulations Process Regulations Chemicals Control Integrated Pollution Control Environmental Quality Regulations A Look to the Future 98 References 99 5 Synthesis of Sitagliptin, the Active Ingredient in Januvia and Janumet 101 Jaume Balsells, Yi Hsiao, Karl B. Hansen, Feng Xu, Norihiro Ikemoto, Andrew Clausen, and Joseph D. Armstrong III 5.1 Introduction First-Generation Route Sitagliptin through Diastereoselective Hydrogenation of an Enamine. The PGA Enamine-Ester Route The Triazole Fragment Direct Preparation of β-keto Amides Second-Generation Chiral Auxiliary Route. The PGA Enamine-amide Route The Asymmetric Hydrogenation Route Purification and Isolation of Sitagliptin (Pharmaceutical Form) The Final Manufacturing Route 123 Acknowledgments 125 References The Development of Short, Efficient, Economic, and Sustainable Chemoenzymatic Processes for Statin Side Chains 127 Martin Schürmann, Michael Wolberg, Sven Panke, and Hans Kierkels 6.1 Introduction: Biocatalysis The Relevance of Statins Biocatalytic Routes to Statin Side Chains Deoxy-d-Ribose 5-Phosphate Aldolase (DERA)-Based Routes to Statin Intermediates Chemical Transformations of the DERA Product Toward Statins Optimization and Scale-Up of the DERA Reaction Deactivation of DERA Enzyme Kinetics Conclusions and Outlook Improvement of DERA by Directed Evolution Conclusions 142 Acknowledgments 143 References 143

4 X Contents 7 The Taxol Story Development of a Green Synthesis via Plant Cell Fermentation 145 Pia G. Mountford 7.1 Introduction Discovery and Early Development From Extraction of Taxol from Pacific Yew Tree Bark to Semi- Synthetic Taxol Taxol from Plant Cell Fermentation Comparison of Semi-Synthetic versus PCF Taxol Processes: The Environmental Impact Semi-Synthetic Process Taxus Baccata Plantations Biomass Waste from Isolating 10-DAB Chemical Synthesis Plant Cell Fermentation Process Plant Cell Fermentation Crude Paclitaxel Isolation Chromatographic Purification of Crude Paclitaxel Comparison of Semi-Synthetic versus PCF Taxol : Green Chemistry Principles Reagent Use Solvent Use Energy and Handling Implications Final Words 158 Acknowledgments 158 References The Development of a Green, Energy Efficient, Chemoenzymatic Manufacturing Process for Pregabalin 161 Peter J. Dunn, Kevin Hettenbach, Patrick Kelleher, and Carlos A. Martinez 8.1 Introduction Process Routes to Pregabalin Classical Resolution Route Asymmetric Hydrogenation Route to Pregabalin Non-Pfizer/Parke-Davis Routes to Pregabalin Biocatalytic Route to Pregabalin Enzyme Screening, Optimization, and Recycling of Undesired Enantiomer Subsequent Chemical Steps to Pregabalin Green Chemistry Considerations Material Usage Energy Usage Conclusions 176 Acknowledgments 176 References 176

5 Contents XI 9 Green Processes for Peptide Mimetic Diabetic Drugs 179 Yasuhiro Sawai and Mitsuhisa Yamano 9.1 Introduction Green Chemistry Considerations in Peptide-like API Manufacture Purification Process to Manufacture Amorphous API Cation Exchange Chromatography Extraction Preparation of Unnatural Amino Acids Crystallization-Induced Diastereomer Transformation Optical Resolution via Diastereomeric Salt Formation Summary 193 Acknowledgments 193 References The Development of an Environmentally Sustainable Process for Radafaxine 197 Trevor Grinter 10.1 Introduction Background Chemistry Process and the Dynamic Kinetic Resolution (DKR) General Description of the Chemistry Route Route Multicolumn Chromatography Development of Route Environmental Assessment Life Cycle Metrics Eco-Efficiency Benefits Summary 217 Acknowledgments 218 References Continuous Processing in the Pharmaceutical Industry 221 Lee Proctor, Peter J. Dunn, Joel M. Hawkins, Andrew S. Wells, and Michael T. Williams 11.1 Introduction Continuous Production of a Key Intermediate for Atorvastatin Laboratory Screening Reaction Scale-up Product Isolation and Waste Treatment Continuous Process to Prepare Celecoxib Continuous Oxidation of Alcohols to Aldehydes Continuous Production of Bromonitromethane Continuous Production and Use of Diazomethane A Snapshot of Some Further Continuous Processes Used in the Preparation of Pharmaceutical Agents 238

6 XII Contents 11.8 Conclusions 241 Acknowledgments 241 References Preparative and Industrial Scale Chromatography: Green and Integrated Processes 243 Eric Lang, Eric Valéry, Olivier Ludemann-Hombourger, Wieslaw Majewski, and Jean Bléhaut 12.1 Introduction Basic Principles of Chromatography Process Optimization to Reduce Eluent Consumption Batch Processes Increasing Injected Amount Reducing Cycle Time with Stacked Injections (Case of Isocratic Eluents) Reducing Cycle Time Using Gradients Continuous Processes Use of a Green Solvent: Supercritical Carbon Dioxide Solvent Recycling Technologies Recycling Devices for Isocratic Chromatography Recycling Devices for Gradient Chromatography Recycling Devices for Supercritical Carbon Dioxide Application Examples Optimization of a Batch Process Selection of the Chromatographic Conditions Scale-up on a Pilot SFC Unit Optimization of an MCC Process Conclusion: An Environmentally Friendly Solution for Each Separation 264 Acknowledgment 266 References Dynamic Resolution of Chiral Amine Pharmaceuticals: Turning Waste Isomers into Useful Product 269 John Blacker and Catherine E. Headley 13.1 Background Chiral Amine Resolution Processes Homochiral Amine Racemization Processes Integration of Chiral Amine Resolution and Racemization Dynamic Resolution Processes Case Studies Asymmetric Transformation of (S)-7-Methoxy-1,2,3,4-tetrahydronaphthalen-2-amine Asymmetric Transformation of (R)-1-tert-butyloxycarbonyl-3-aminopyrrolidine 281

7 Contents XIII Sertraline Conclusions 286 Acknowledgments 287 References Green Technologies in the Generic Pharmaceutical Industry 289 Apurba Bhattacharya and Rakeshwar Bandichhor 14.1 Introduction Waste : Definition and Remedy Amidation Carbodiimide and Acid Chloride Mediated Transformation Metal-Catalyzed Oxidative Amide Synthesis Copper-Catalyzed Amide Synthesis Palladium-Catalyzed Amide Synthesis Ruthenium-Catalyzed Amide Synthesis N-Heterocyclic Carbene (NHC-Catalyzed Amidation) Amidation Catalyzed by Boric Acid Derivatives Synthesis of Galanthamine Synthesis of Solefinacin Precedented Approach A Greener Approach Synthesis of Levetiracetam Established Approach A More Eco-Friendly Synthesis Synthesis of a Finasteride Intermediate The Classical Approach Problems with the Existing Synthesis A Catalytic Approach Bromination Current Zafirlukast Bromination Method Environmental Burden Waste-Minimized Bromination Sulfoxidation in the Synthesis of Rabeprazole The Traditional Approach A Greener Approach Conclusions 307 Acknowledgments 308 References Environmental Considerations in Biologics Manufacture 311 Sa V. Ho 15.1 Introduction Therapeutic Biologics Types of Therapeutic Biologics General Features of Therapeutic Protein Manufacture 314

8 XIV Contents 15.3 Environmental Impact Considerations Microbially Produced Proteins Insulin Production Process Production of a Typical Medium-Sized Protein Highly Efficient Protein Manufacturing Process Monoclonal Antibodies and Mammalian Cell Culture Processes Typical-to-Optimized Manufacturing Process for mabs Projected Intensified Large-Scale Monoclonal Antibody Manufacturing Process Overall Comparison Environmental Indices for Therapeutic Protein Manufacture Technologies with Potential Environmental Impact Single-Use Biologics Manufacture Summary 329 Acknowledgments 330 References Future Trends for Green Chemistry in the Pharmaceutical Industry 333 Peter J. Dunn, Andrew S. Wells, and Michael T. Williams 16.1 Introduction Waste Minimization in Drug Discovery Greener Synthetic Methods in Primary Manufacturing Synthesis Design and Execution Reduction and Oxidation C C Bond Formation Heteroatom Alkylation and Acylation Biocatalysis Now and Into the Future Application of Technology Alternative Solvents in the Pharmaceutical Industry Water Ionic Liquids (ILs) Fluorous Solvents Supercritical CO 2 (SC-CO 2 ) and Gas-Expanded Liquids (GXL) Molecular Solvents from Renewable Sources Solid-Phase Reactions The Work-Up Obstacles to Change Green Chemistry in Secondary Pharmaceutical Operations Global Cooperation in Green Chemistry The Pharmaceutical Roundtable Recognition The Global Impact Conclusions 353 References 353 Index 357