Details

Asymmetric Catalysis on Industrial Scale

Challenges, Approaches and Solutions
2. Aufl.

von: Hans Ulrich Blaser, Hans-Jürgen Federsel
198,99 €
Verlag:	Wiley-VCH (D)
Format:	EPUB
Veröffentl.:	04.08.2011
ISBN/EAN:	9783527642168
Sprache:	englisch
Anzahl Seiten:	580

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Beschreibungen

Titelbeschreibung

This second edition of the pioneering work on this hot topic captures the major trends and latest achievements in the art of asymmetric catalysis on an industrial scale. A number of completely new real-life case studies written by the world leaders in their respective areas provide a compact and qualified insight into this developing field. The resulting ready reference and handbook collates first-hand and valuable information within a context where it can be easily found. The high-quality contributions illustrate the relevant environments and situations, such as time pressure, how the catalytic step fits into the overall synthesis, or competition with other synthetic approaches, as well as the typical problems encountered in the various phases, including finding/developing the catalyst and optimization of the process or choice of equipment. Both successful and unsuccessful approaches to solve these problems are described.

Inhaltsverzeichnis

PART I: New Processes for Existing Active Compounds (APIs) SOME RECENT EXAMPLES IN DEVELOPING BIOCATALYTIC PHARMACEUTICAL PROCESSES Introduction Levetiracetam (Keppra?) Atorvastatin (Lipitor?) Pregabalin (Lyrica?) Conclusion ENANTIOSELECTIVE HYDROGENATION: APPLICATIONS IN PROCESS R&D OF PHARMACEUTICALS Introduction Carbonyl Hydrogenations Imine Hydrogenation Conclusion CHIRAL LACTONES BY ASYMMETRIC HYDROGENATION - A STEP FORWARD IN (+)-BIOTIN PRODUCTION Introduction: (+)-Biotin as an Example for the Industrial Production of Vitamins Commercial Syntheses and Other Routes to (+)-Biotin by Total Synthesis Catalytic Asymmetric Reduction of Cyclic Anhydride to D-Lactone Conclusion BIOCATALYTIC ASYMMETRIC OXIDATION FOR THE PRODUCTION OF BICYCLIC PROLINE PEPTIDOMIMETICS Introduction Development of Routes to 1 and 2 Asymmetric Biocatalytic Amine Oxidation Enzyme Evolution - Current State of the Art Amine Oxidase Evolution Chemical Development Optimization of Cyanation Conclusion THE ASYMMETRIC REDUCTION OF HETEROCYCLIC KETONES - A KEY STEP IN THE SYNTHESIS OF POTASSIUM-COMPETITIVE ACID BLOCKERS (P-CABs) Potassium-Competitive Acid Blockers - A New Option for the Treatment of Acid-Related Diseases Discovery and Development of 7H-8,9-Dihydropyrano[2,3-c]imidazo[1,2-a]pyridines as Potassium-Competitive Acid Blockers Noyori-Type Catalysts for the Asymmetric Reduction of Prochiral Ketones Research Overview Asymmtric Reduction of Ketones Bearing the Imidazo[1,2-a]pyridine Skeleton Asymmetric Reduction of Ketones Bearing the 3,6,7,8-Tetrahydrochromenol[7,8-d]imidazole Skeleton Large-Scale Asymmetric Synthesis of the 3,6,7,8-Tetrahydrochromeno[7,8-d]imidazole BYK 405879 Conclusions PART II: Processes for Important Building Blocks APPLICATION OF A MULTIPLE-ENZYME SYSTEM FOR CHIRAL ALCOHOL PRODUCTION Introduction Construction of an Enzymatic Reduction System Enzymatic Stereoinversion System CHEMOENZYMATIC ROUTE TO THE SIDE-CHAIN OF ROSUVASTATIN Introduction Route Selection Process Development Conclusion ASYMMETRIC HYDROGENATION OF A 2-ISOPROPYLCINNAMIC ACID DERIVATIVE EN ROUTE TO THE BLOOD PRESSURE-LOWERING AGENT ALISKIREN Introduction Development of Monodentate Phosphoramidites as Ligands for Asymmetric Hydrogenation Instant Ligand Libraries of Monodentate BINOL-Based Phosphoramidites Aliskiren High-Throughput Screening in Search of a Cheap Phosphoramidite Ligand Mixtures of Ligands Further Screening of Conditions Validation and Pilot Plant Run Instant Ligand Library Screening to Further Optimize Rate and ee Validations Recent Developments in the Asymmetric Hydrogenation of 3 Conclusion ASYMMETRIC PHASE-TRANSFER CATALYSIS FOR THE PRODUCTION OF NON-PROTEINOGENIC ALPHA-AMINO ACIDS Background Designer's Chiral Phase-Transfer Catalysts Cynthesis of the C2-Symmetric Chiral Mono-1,1'-Binaphthyl-Derived Catalyst Application of Enantiomers of 21 to the Industrial Production of NPAAs Conclusion DEVELOPMENT OF EFFICIENT TECHNICAL PROCESSES FOR THE PRODUCTION OF ENANTIOPURE AMINO ALCOHOLS IN THE PHARMACEUTICAL INDUSTRY Introduction Phenylephrine Adrenaline (Epinephrine) Lobeline Availability of the Catalyst General Remarks on the Development of Industrial Processes for Asymmetric Hydrogenation THE ASYMMETRIC HYDROGENATION OF ENONES - ACCESS TO A NEW L-MENTHOL SYNTHESIS Introduction Screening of Metal Complexes, Conditions, and Ligands Scale-Up and Mechanistic Work Catalyst Recycling and Continuous Processing Conclusion ELIMINATING BARRIERS IN LARGE-SCALE ASYMMETRIC SYNTHESIS Introduction Improvement of the Synthetic Route to Biaryl Ligands Development of an Efficient Process En Route to Unprotected Beta-Amino Acids Conclusion CATALYTIC ASYMMETRIC RING OPENING: A TRANSFER FROM ACADEMIA TO INDUSTRY Introduction Catalyst Preparation and Initial Optimization Further Optimization Process Adaptation Protecting Group Adaption Use of Benzoate as O-Nucleophile Chemical Elaboration Conclusion ASYMMETRIC BAEYER-VILLIGER REACTIONS USING WHOLE-CELL BIOCATALYSTS Introduction Chemistry Biocatalysts Process Screening and Design Downstream Processing Future Process Developments Perspective LARGE-SCALE APPLICATIONS OF HYDROLASES IN BIOCATALYTIC ASYMMETRIC SYNTHESIS Introduction Chemistry Biocatalyst Process Screening and Design Downstream Processing and Purification Future Process Developments Perspectives SCALE-UP STUDIES IN ASYMMETRIC TRANSFER HYDROGENATION Background Reaction Components Case Studies Conclusions 2,2',5,5'-TETRAMETHYL-4,4'-BIS(DIPHENYLPHOSHINO)-3,3'-BITHIOPHENE: A VERY EFFICIENT CHIRAL LIGAND FOR RU-CATALYZED ASYMMETRIC HYDROGENATIONS ON THE MULTI-KILOGRAMS SCALE Introduction Case Histories Conclusion THE POWER OF WHOLE-CELL REACTION: EFFICIENT PRODUCTION OF HYDROPYROLINE, SUGAR NUCLEOTIDES, OLIGOSACCHARIDES, AND DIPEPTIDES Introduction Production of Hydroxyproline by Asymmetric Hydroxylation of L-Proline Oligosaccharide Production by Bacterial Coupling Dipeptide Production Systems Conclusion and Perspective ENANTIOSELECTIVE KETONE HYDROGENATION: FROM RESEARCH TO PILOT SCALE WITH INDUSTRIALLY VIABLE RU/PHOSPHINE-OXAZOLINE) COMPLEXES Introduction Ligand Screening and Optimization of the Reaction Conditions Quality Risks Health and Safety Catalyst Removal Final Process PART III: Processes for New Chemical Entities (NCEs) ENABLING ASYMMETRIC HYDROGENATION FOR THE DESIGN OF EFFICIENT SYNTHESIS OF DRUG SUBSTANCES Introduction Laropiprant Taranabant Sitagliptin Conclusions and Outlook SCALE-UP OF A TELESCOPED ENZYMATIC HYDROLYSIS PROCESS FOR AN INTERMEDIATE IN THE SYNTHESIS OF A FACTOR Xa INHIBITOR Introduction The Discovery Chemistry Synthesis Optimization and Multi-Kilogram Supply of Monoacid (R,R)-2 Process Development of the N-Boc Approach Scalable Enzymatic Monohydrolysis of the Diester (R,R)-1 Production - Experimental Part Evaluation of an Enzymatic Alternative - The N-Difluoroethyl Approach Discussion AN EFFICIENT, ASYMMETRIC SYNTHESIS OF ODANACATIB, A SELECTIVE INHIBITOR OF CATHEPSIN K FOR THE TREATMENT OF OSTEOPOROSIS, USING AN ENZYME-MEDIATED DYNAMIC KINETIC RESOLUTION Introduction Fluoroleucine Synthesis Strategy First-Generation Enzymatic Dynamic Kinetic Resolution: Batch Process Development of Enzymatic Dynamic Kinetic Resolution: Towards a Manufacturing Process Pilot Plant Runs Conclusion BIOCATALYTIC ROUTES TO THE GPIIb/IIIa ANTAGONIST LOTRAFIBAN, SB 214857 Introduction The Medicinal Chemistry Route of Synthesis The First Biocatalytic Route - A Late-Stage Resolution Early-Stage Resolution Catalase for the Removal of Iodide Other Synthetic Strategies to Chiral Lotrafiban Intermediates The End Game DISCOVERY AND DEVELOPMENT OF A CATALYTIC ASYMMETRIC CONJUGATE ADDITION TO KETOESTERS TO NITROALKENES AND ITS USE IN THE LARGE-SCALE PREPARATION OF ABT-546 Introduction Retrosynthetic Analysis of ABT-546 Early Asymmetric Syntheses Synthesis of the Reaction Partners Discovery of the Asymmetric Conjugate Addition Reaction Completion of the Synthesis of ABT-546 Extension to Other Reaction Partners Conclusion THE KAGAN OXIDATION - INDUSTRIAL-SCALE ASYMMETRIC SULFOXIDATIONS IN THE SYNTHESIS OF TWO RELATED NK1/NK2 ANTAGONISTS Introduction Background and Introduction to ZD7944 Introduction to the ZD7944 CBz Sulfoxide Stage Process Development of ZD7944 CBz Sulfoxide Additional Investigations in the Development of ZD7944 CBz Sulfoxide The Impact of Other Stages on the ZD7944 CBz Sulfoxide Process Summary of ZD7944 Background and Introduction to ZD2249 Process Development of ZD2249 CBz Sulfoxide Summary of ZD2249 Comparison and Conclusion LARGE-SCALE APPLICATION OF ASYMMETRIC PHASE-TRANSFER CATALYSIS FOR AMINO ACID SYNTHESIS Introduction Initial Strategy Synthesis of 4,4'-Difluorobenzylhydryl Bromide Initial Studies and Optimization Scale-Up of the PTC Alkylation Conclusion Experimental APPLICATION OF PHASE-TRANSFER CATALYSIS IN THE ORGANOCATALYTIC ASYMMETRIC SYNTHESIS OF AN ESTROGEN RECEPTOR BETA-SELECTIVE AGONIST Introduction Medicinal Chemistry Synthesis and Revised Synthetic Plan Preparation of the Phase-Transfer Substrate 11 Asymmetric Phase-Transfer Michael Addition Ether Cleavage, Cyclization, and Chlorination Conclusion ASYMMETRIC SYNTHESIS OF HCVAND HPV DRUG CANDIDATES ON SCALE: THE CHOICE BETWEEN ENANTIOSELECTIVE AND DIASTEREOSELECTIVE SYNTHESES Introduction GSK260983A (1) for the HPV GSK873082X (2) for the HCV Conclusion

Rezension

"Overall, this book will be of interest to both industrial specialists and academics as it contains a good mix of chemistry and engineering. It provides comfort and inspiration to those working in this field through the numerous success stories told and is undoubtedly a useful source of potential contacts for those struggling with a particular asymmetric synthesis issue." (Platinum Metals Review, 2011)

Autorenportrait

Hans-Ulrich Blaser carried out his doctoral research with A. Eschenmoser at the Federal Institute of Technology (ETH) Zurich, where he received the Ph.D. degree in 1971. Between 1971 and 1975 he held postdoctoral positions at the University of Chicago (J. Halpern), Harvard University (J.A. Osborn), and Monsanto (Zurich). During 20 years at Ciba-Geigy (1976-1996) he gained practical experience at R&D in the fine chemicals and pharmaceutical industry, which continued at Novartis (1996-1999) and at Solvias where he presently is chief technology officer. Hans-Jurgen Federsel is a renowned specialist in the field of process R&D with a professional career spanning over 30 years. Starting off as bench chemist in Astra at the major Swedish site in Sodertalje, he climbed the ranks to occupy positions both as line and project manager. After the merger that formed AstraZeneca, he became Head of Projects Management at the aforementioned location and was then appointed to the newly created role as Director of Science in Global Process R&D in 2004. In connection with this, he was also given the prestigious title Senior Principal Scienstist. His strong academic links have been further developed over the years after obtaining the PhD in Organic Chemistry at the Royal Institute of Technology in Stockholm, which was led to his being awarded an Associate Professorship there. His long-lasting links to this Institute has brought him a seat on the Board of the School of Chemical Science and Engineering from 2005. Publishing in peer reviewed journals and books and frequent lecturing has rendered fame to his name that goes far beyond the limits of the own company and Dr. Federsel enjoys invitations from all over the world to share learning and experience from his broad knowledge base on process R&D. In 2009 he was elected to the Royal Swedish Academy of Engineering Sciences (IVA).

Back cover copy

The quest for making molecules in a stereochemically-defined manner continues without any signs of a loss of interest. This is particularly true of the pharmaceutical and fine chemicals industries, and this has fueled the search for novel technologies and methods to achieve this, both in academiaa nd within the industry. This second collection of case studies captures the trends and major achievements in the art of making chiral chemical compounds on an industrial scale. Included is the development of as many large-scale enantioselective processes as possible, showing the "real life" applications of this challenging field. As a result, first-hand and valuable information is collated within the one monograph where it can be easily accessible. The contributions illustrate the relevant environments and situations, such as time pressure, the fit of the catalytic step into the over-all synthesis, or competition with other synthetic approaches, as well as the typical problems encountered in the various phases, such as finding/developing the catalyst, optimization of the process or choice of equipment, etc.