Green Chemistry in the Pharmaceutical Industry (PDF)

INTRODUCTION TO GREEN CHEMISTRY, ORGANIC SYNTHESIS AND PHARMACEUTICALS 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 AND JANUMET 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-Amide Route Prufication and Isolation of Sitagliptin (Pharmaceutical Form) The Final Manufacturing Route THE DEVELOPMENT OF SHORT, EFFICIENT, ECONOMIC, AND SUSTAINABLE CHEMOENZYMATIC 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 Statin Intermediates Conclusions THE TAXOL STORY-DEVELOPMENT OF A GREEN SYNTHESIS VIA PLANT CELL FERMENTATION Introduction Discovery and Early Development From Extraction of Taxol from Pacific Yew Tree Bark to Semi-Synthetic Taxol Taxol from Plant Cell Fermentation

Peter Dunn received his PhD from Imperial College London in 1987 working under the supervision of Professor Charles Rees. Postdoctoral work followed with Prof. Albert Eschenmoser at the ETH, Zurich and with Prof. Henry Rapaport at the University of California, Berkeley. In 1989 he joined Pfizer and was involved with the invention of the commercial processes to make several medicines including "Viagra", Emselex, Revation and Sampatrilat. In 2000 he became Director of Chemical R & D at Pfizer and was responsible for the filing and transfer to manufacturing of human and animal medicines such as Voriconazole, Darifenacin, Fosfluconazole and Dirlotapide. In 2006 he took up his current role as Global Green Chemistry lead for Pfizer. He is currently co-chair of the Green Chemistry Institute Pharmaceutical Roundtable and a member of the editorial board for the journal of Green Chemistry.

Andrew Wells obtained his PhD in organophosphorous and organometallic chemistry from Essex University, before joining the Chemical Development Group of SmithKline & French in 1986, which later became SmithKline Beecham. In 1999 he received a SKB corporate award for green chemistry/technology. In 2000, he joined AstraZeneca in Global Process R & D where he is currently a Senior Principal Scientist and heads the AZ GPRD Green Chemistry group. He is an active member of the ACS Green Chemistry Institute Pharmaceutical Roundtable and has acted as an advisor to the UK Chemical Innovation Knowledge Transfer Network and the UK Technology Strategy Board. A keen supporter of the industry-academia interface, having been involved closely with several major collaborations such as the Centre for Biocatalysis at Manchester and the Institute of Process R & D at Leeds University, he has also been an industrial supervisor to around 20 PhD and MSc students.

Michael Williams obtained his chemistry BSc from King's College, London, and spent time as a medicinal chemist at ICI Pharmaceuticals (Alderley

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