Asymmetric Catalysis on Industrial Scale

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.

Die zweite Auflage dieser bahnbrechenden Publikation zur industriellen asymmetrischen Katalyse fängt die wichtigsten Trends und aktuellen Entwicklungen ein. Komplett neue Fallstudien weltweit führender Fachleute bieten Ihnen einen kompakten und kompetenten Einblick in das Gesamtgebiet.

PART I: New Processes for Existing Active Compounds (APIs)SOME RECENT EXAMPLES IN DEVELOPING BIOCATALYTIC PHARMACEUTICAL PROCESSESIntroductionLevetiracetam (Keppra®)Atorvastatin (Lipitor®)Pregabalin (Lyrica®)ConclusionENANTIOSELECTIVE HYDROGENATION: APPLICATIONS IN PROCESS R&D OF PHARMACEUTICALSIntroductionCarbonyl HydrogenationsImine HydrogenationConclusionCHIRAL LACTONES BY ASYMMETRIC HYDROGENATION - A STEP FORWARD IN (+)-BIOTIN PRODUCTIONIntroduction: (+)-Biotin as an Example for the Industrial Production of VitaminsCommercial Syntheses and Other Routes to (+)-Biotin by Total SynthesisCatalytic Asymmetric Reduction of Cyclic Anhydride to D-LactoneConclusionBIOCATALYTIC ASYMMETRIC OXIDATION FOR THE PRODUCTION OF BICYCLIC PROLINE PEPTIDOMIMETICSIntroductionDevelopment of Routes to 1 and 2Asymmetric Biocatalytic Amine OxidationEnzyme Evolution - Current State of the ArtAmine Oxidase EvolutionChemical DevelopmentOptimization of CyanationConclusionTHE 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 DiseasesDiscovery and Development of 7H-8,9-Dihydropyrano[2,3-c]imidazo[1,2-a]pyridines as Potassium-Competitive Acid BlockersNoyori-Type Catalysts for the Asymmetric Reduction of Prochiral KetonesResearch OverviewAsymmtric Reduction of Ketones Bearing the Imidazo[1,2-a]pyridine SkeletonAsymmetric Reduction of Ketones Bearing the 3,6,7,8-Tetrahydrochromenol[7,8-d]imidazole SkeletonLarge-Scale Asymmetric Synthesis of the 3,6,7,8-Tetrahydrochromeno[7,8-d]imidazole BYK 405879ConclusionsPART II: Processes for Important Building BlocksAPPLICATION OF A MULTIPLE-ENZYME SYSTEM FOR CHIRAL ALCOHOL PRODUCTIONIntroductionConstruction of an Enzymatic Reduction SystemEnzymatic Stereoinversion SystemCHEMOENZYMATIC ROUTE TO THE SIDE-CHAIN OF ROSUVASTATINIntroductionRoute SelectionProcess DevelopmentConclusionASYMMETRIC HYDROGENATION OF A 2-ISOPROPYLCINNAMIC ACID DERIVATIVE EN ROUTE TO THE BLOOD PRESSURE-LOWERING AGENT ALISKIRENIntroductionDevelopment of Monodentate Phosphoramidites as Ligands for Asymmetric HydrogenationInstant Ligand Libraries of Monodentate BINOL-Based PhosphoramiditesAliskirenHigh-Throughput Screening in Search of a Cheap Phosphoramidite LigandMixtures of LigandsFurther Screening of ConditionsValidation and Pilot Plant RunInstant Ligand Library Screening to Further Optimize Rate and eeValidationsRecent Developments in the Asymmetric Hydrogenation of 3ConclusionASYMMETRIC PHASE-TRANSFER CATALYSIS FOR THE PRODUCTION OF NON-PROTEINOGENIC ALPHA-AMINO ACIDSBackgroundDesigner's Chiral Phase-Transfer CatalystsCynthesis of the C2-Symmetric Chiral Mono-1,1'-Binaphthyl-Derived CatalystApplication of Enantiomers of 21 to the Industrial Production of NPAAsConclusionDEVELOPMENT OF EFFICIENT TECHNICAL PROCESSES FOR THE PRODUCTION OF ENANTIOPURE AMINO ALCOHOLS IN THE PHARMACEUTICAL INDUSTRYIntroductionPhenylephrineAdrenaline (Epinephrine)LobelineAvailability of the CatalystGeneral Remarks on the Development of Industrial Processes for Asymmetric HydrogenationTHE ASYMMETRIC HYDROGENATION OF ENONES - ACCESS TO A NEW L-MENTHOL SYNTHESISIntroductionScreening of Metal Complexes, Conditions, and LigandsScale-Up and Mechanistic WorkCatalyst Recycling and Continuous ProcessingConclusionELIMINATING BARRIERS IN LARGE-SCALE ASYMMETRIC SYNTHESISIntroductionImprovement of the Synthetic Route to Biaryl LigandsDevelopment of an Efficient Process En Route to Unprotected Beta-Amino AcidsConclusionCATALYTIC ASYMMETRIC RING OPENING: A TRANSFER FROM ACADEMIA TO INDUSTRYIntroductionCatalyst Preparation and Initial OptimizationFurther OptimizationProcess AdaptationProtecting Group AdaptionUse of Benzoate as O-NucleophileChemical ElaborationConclusionASYMMETRIC BAEYER-VILLIGER REACTIONS USING WHOLE-CELL BIOCATALYSTSInt