Stereoisomers large-scale synthesis

Thus, the need has arisen for larger amounts of unnatural amino acids—those that contain unusual side chains or are in the D-series. Because a-amino acids contain an epimerizable center, D-amino acids are usually accessible through epimerization of the natural isomer, followed by a resolution. Of course, the racemic mixture can also be accessed by synthesis. Because resolution can be either wasteful—if the undesired isomer is discarded—or clumsy—when the other isomer is recycled through an epimerization protocol—many large-scale methods now rely on a dynamic resolution, where all of the starting material is converted to the desired isomer (vide infra, Chapters 6 and 7). With the advent of asymmetric reactions that can be performed at large scale, a substrate can now be converted to the required stereoisomer without the need for any extra steps associated with a resolution approach. 

Based on these biological data, two commercial forms of a-tocopherol (or their more stable acetate derivatives) are currently being produced by independent approaches [7, 8], Totally synthetic vitamin E, which is an equimolar mixture of all eight stereoisomers of a-tocopherol, is produced at a rate of over 25000 tons per year for the application in feed, food, and the pharma industry. The large-scale industrial synthesis of (all-rac)-a-tocopherol uses 2,3,5-trimethylhydroquinone (11) as the aromatic building block and the C2o compound isophytol (12). The acid-catalyzed condensation reaction in the last step delivers (all-rac)-3 (Fig. 2) [21-25],... 

Because of the specificity and the enantioselectivity of some enzyme-catalyzed reactions, the application of enzymes is increasingly important in asymmetric induction and kinetic resolution in organic synthesis. A large number of publications were recently reviewed, focusing on utilization of enzymes and microorganisms to stereospecific hydrolysis and other reactions to produce pure stereoisomers (2,3). However, the use of an enzyme as a catalyst has usually been limited to small-scale experiments in the laboratory. 

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