Green Chemistry in the Pharmaceutical Industry 论文

详细信息

发表日期

2010-03-10

发表年份

2010

摘要

INTRODUCTION TO GREEN CHEMISTRY, ORGANIC SYNTHESIS ANDPHARMACEUTICALS 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 GREEN CHEMISTRY METRICS Introduction Measuring Resource Usage Life Cycle Assessment (LCA) Measuring Chemistry and Process Efficiency Measuring Process Parameters and Emissions Real Time Analysis Operational Efficiency Measuring Energy Measuring the Toxicity of All the Substrates Measuring Degradation Potential Measuring the Inherent Safety of Lack of Inherent Safety Conclusions SOLVENT USE AND WASTE ISSUES Introduction to Solvent Use and Waste Issues Solvent and Process Greenness Scoring and Selection Tools Waste Minimization and Solvent Recovery ENVIRONMENTAL AND REGULATORY ASPECTS Historical Perspective Pharmaceuticals in the Environment Environmental Regulations A Look to the Future SYNTHESIS OF SITAGLIPTIN, THE ACTIVE INGREDIENT IN JANUVIA ANDJANUMET Introduction First-Generation Route Sitagliptin through Diastereoselective Hydrogenation of an Enamine.The PGA Enamine-Ester Route The Triazole Fragment Direct Preparation of Beta-Keto Amides Second-Generation Chiral Auxiliary Route. The PGA Enamine-AmideRoute Prufication and Isolation of Sitagliptin (PharmaceuticalForm) The Final Manufacturing Route THE DEVELOPMENT OF SHORT, EFFICIENT, ECONOMIC, AND SUSTAINABLECHEMOENZYMATIC PROCESSES FOR STATIN SIDE CHAINS Introduction: Biocatalysis The Relevance of Statins Biocatalytic Routes to Statin Side Chains 2-Deoxy-D-Ribose 5-Phosphate Aldolase (DERA)-Based Routes to StatinIntermediates Conclusions THE TAXOL STORY-DEVELOPMENT OF A GREEN SYNTHESIS VIA PLANT CELLFERMENTATION Introduction Discovery and Early Development From Extraction of Taxol from Pacific Yew Tree Bark toSemi-Synthetic Taxol Taxol from Plant Cell Fermentation Comparison of Semi-Synthetic versus PCF Taxol Processes: TheEnvironmental Impact Comparison of Semi-Synthetic versus PCF Taxol: Green ChemistryPrinciples Final Words THE DEVELOPMENT OF A GREEN, ENERGY EFFICIENT, CHEMOENZYMATICMANUFACTURING PROCESS OF PREGABALIN Introduction Process Routes to Pregabalin Biocatalytic Route to Pregabalin Green Chemistry Considerations Conclusions GREEN PROCESSES FOR PEPTIDE MIMETIC DIABETIC DRUGS Introduction Green Chemistry Considerations in Peptide-like APImanufacture Purification Process to Manufacture Amorphous API Preparation of Unnatural Amino Acids Summary THE DEVELOPMENT OF AN ENVIRONMENTALLY SUSTAINABLE PROCESS FORRADAFAXINE Introduction Chemistry Process and the Dynamic Kinetic Resolution (DKR) Multicolumn Chromatography ? Development of Route 4 Environmental Assessment Summary CONTINUOUS PROCESSING IN THE PHARMACEUTICAL INDUSTRY Introduction Continuous Production of a Key Intermediate for Atorvastatin Continuous Process to Prepare Celecoxib Continuous Oxidation of Alcohols to Aldehydes Continuous Production of Bromonitromethane Continuous Production and Use of Diazomehtane A Snapshot of Some Further Continuous Processes Used in thePreparation of Pharmaceutical Agents Conclusions PREPARATIVE AND INDUSTRIAL SCALE CHROMATOGRAPHY: GREEN ANDINTEGRATED PROCESSES Introduction Basic Principles of Chromatography Process Optimization to Reduce Eluent Consumption Use of a Green Solvent: Supercritical Carbon Dioxide Solvent Recycling Technologies Application Examples Conclusion: An Environmentally Friendly Solution for EachSeparation DYNAMIC RESOLUTION OF CHIRAL AMINE PHARMACEUTICALS: TURNING WASTEISOMERS INTO USEFUL PRODUCT Background Integration of Chiral Amine Resolution and Racemization Case Studies Conclusions GREEN TECHNOLOGIES IN THE GENERIC PHARMACEUTICAL INDUSTRY Introduction 'Waste': Definition and Remedy Amidation Synthesis of Galanthamine Synthesis of Solefinacin Synthesis of Levetiracetam Synthesis of a Finasteride Intermediate Bromination Sulfoxidation in the Synthesis of Rabeprazole Conclusions ENVIRONMENTAL CONSIDERATIONS IN BIOLOGICS MANUFACTURE Introduction Therapeutic Biologics Environmental Impact Considerations Overall Comparison Environmental Indices for Therapeutic Protein Manufacture Technologies with Potential Environmental Impact Single-Use Biologics Manufacture Summary FUTURE TRENDS FOR GREEN CHEMISTRY IN THE PHARMACEUTICALINDUSTRY Introduction Waste Minimization in Drug Discovery Greener Synthetic Methods in Primary Manufacturing Alternative Solvents in the Pharmaceutical Industry Green Chemistry in Secondary Pharmaceutical Operations Global Cooperation in Green Chemistry Conclusions