Asymmetric chiral drugs

Asymmetric synthesis is a stimulating academic challenge, but since it has become clear that most chiral drugs can be administered safely only in the enantiomerically pure form, the industrial need for asymmetric methods has made research in asymmetric synthesis absolutely necessary [5]. This has driven a renaissance in the discipline of organic chemistry, because all of the old-established reactions need to be reinvestigated for their application in asymmetric synthesis [6]. This has also applied... 

A different approach to making chiral drugs is asymmetric synthesis. An optically inactive precursor is converted to the drug by a reaction that uses a special catalyst, usually an enzyme (Chapter 11). If all goes well, the product is a single enantiomer with the desired physiological effect In 2001, William S. Knowles, Ryogi Noyori, and K. Barry Sharpless won the Nobel Prize in chemistry for work in this area. 

Excellent asymmetric hydrogenation of amino ketones has been applied for the syntheses of many chiral drugs. For example, the enantioselective hydrogenation of 3-aryloxy-2-oxo-l-propylamine derivatives can directly afford the l-amino-3-aryloxy-2-propanol derivatives as chiral / -adrenergic blocking agents. This has been successfully accomplished with a neutral MCCPM-Rh complex as the catalyst. With 0.01 mol.% of an (A,A)-MCCPM-Rh complex,... 

The development of chiral phosphorus ligands has made undoubtedly significant impact on the asymmetric hydrogenation. Transition metal catalysts with efficient chiral phosphorus ligands have enabled the synthesis of a variety of chiral products from prochiral olefins, ketones, and imines in a very efficient manner, and many practical hydrogenation processes have been exploited in industry for the synthesis of chiral drugs and fine chemicals. 

The asymmetric hydrogenation of C=X ti-bonds (X = O, NR) is estimated to account for over half the chiral drugs manufactured industrially, withstanding physical and enzymatic resolution. For selected reviews on C-C bond forming hydrogenation and transfer hydrogenation, see [11-17]. 

The first edition of Catalytic Asymmetric Synthesis, published in the fall of 1993, was very warmly received by research communities in academia and industries from graduate students, research associates, faculty, staff, senior researchers, and others. The book was published at the very moment that the Food Drug Administration (FDA) in the United States clarified the situation in Chiral Drugs, the word chirotechnology was created, and chirotechnology industries were spawning in the United States and Britain. 

R de Souza Pereira. The use of baker s yeast in the generation of asymmetric centers to produce chiral drugs and other compounds. Crit Rev Biotechnol 18 25-83, 1998. 

The majority of the new drugs approved and the most often prescribed drugs in the United States have at least one asymmetric center [169]. Approximately half of these chiral drugs are of a racemic composition. Many of the optically pure drug substances are of natural origin, while the majority of the synthetically derived products are in racemic form [172]. Enantiomers can differ in their pharmacological activity or one may be inactive or... 

D. E. Drayer, The early history of stereochemistry from the discovery of molecular asymmetry and the first resolution of a racemate by Pasteur to the asymmetrical chiral carbon of van t Hoff and le Bel , in Clin. Pharmacol. vol.18, Drug Stereochemistry (2nd edn.), D. E. Drayer and I. W. Weiner, Dekker, New York, NY, 1993, pp. 1-24. 

O Brien, M.K. Vanasse, B. Asymmetric processes in the large-scale preparation of chiral drug... 

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