Optical isomers processes

Crystallization continues to be the most widely used method of separating or resolving enantiomers (optical resolutions). The manufacture of chemicals and pharmaceuticals as purified optical isomers, or enantiomers, has taken on a pivotal importance in the pharmaceutical, agricultural and fine chemicals industries over the past 15-20 years. Crystallization has been and continues to be the most widely used method of separating or resolving enantiomers (optical resolutions), and is particularly well suited to separations at large scale in manufacturing processes (Jacques etal., 1981 Roth etai, 1988 Wood, 1997 Cains, 1999). 

The study of optical isomers has shown a similar development. First it was shown that the reduction potentials of several meso and racemic isomers were different (Elving et al., 1965 Feokstistov, 1968 Zavada et al., 1963) and later, studies have been made of the ratio of dljmeso compound isolated from electrolyses which form products capable of showing optical activity. Thus the conformation of the products from the pinacolization of ketones, the reduction of double bonds, the reduction of onium ions and the oxidation of carboxylic acids have been reported by several workers (reviewed by Feokstistov, 1968). Unfortunately, in many of these studies the electrolysis conditions were not controlled and it is therefore too early to draw definite conclusions about the stereochemistry of electrode processes and the possibilities for asymmetric syntheses. 

The solution to this problem has been to isolate the lactide and to polymerize this directly using a tin(ii) 2-(ethyl)hexanoate catalyst at temperatures between 140 and 160 °C. By controlling the amounts of water and lactic acid in the polymerization reactor the molecular weight of the polymer can be controlled. Since lactic acid exists as d and L-optical isomers, three lactides are produced, d, l and meso (Scheme 6.11). The properties of the final polymer do not depend simply on the molecular weight but vary significantly with the optical ratios of the lactides used. In order to get specific polymers for medical use the crude lactide mix is extensively recrystallized, to remove the meso isomer leaving the required D, L mix. This recrystallization process results in considerable waste, with only a small fraction of the lactide produced being used in the final polymerization step. Hence PLA has been too costly to use as a commodity polymer. 

Toray (1) A large Japanese chemicals manufacturer, perhaps best known for its process for synthesizing /-lysine for use as a dietary supplement. The starting material is cyclohexene which is converted in five steps to racemic lysine. An enzymic process isolates the desired optical isomer, the other is recycled. 

The application of the SMB-technique to the downstream processing of biotechnological products requires some specific changes to meet the special demands of bioproduct isolation. Some exemplary applications are given including separations of sugars, proteins, monoclonal antibodies, ionic molecules and optical isomers and for desalting. 

One application in liquid chromatography which does alter the separation process is the use of a specific series of derivatives to enable the separation of chiral (optical isomers) forms of alcohols, amines and amino acids using reverse-phase separation. FLEC is available in the two chiral forms (+)-l-(9-fluorenyl) ethyl chloroformate and (—)-l-(9-fluorenyl) ethyl chlorofor-mate (Figure 3.12). Reaction of two stereoisomers of a test compound (e.g. T+ and T—) with a single isomer of the derivatizing reagent (e.g. R+) will result in the formation of two types of product, T+R+ and T—R+. It is possible to separate these two compounds by reverse-phase chromatography. 

The growing interest in supramolecular chirality stems not only from the intrinsic relevance of such studies for the origin of chirality in life processes, but also from the potential technological applications, such as the separation of optical isomers for the pharmaceutical or food industries. 

The process of racemization has a number of practical application in the laboratory and in industry. Thus, in the synthesis of an optical isomer it is frequently possible to racemize the unwanted isomer and to separate additional quantities of the desired isomer. By repeating this process a number of times it is theoretically possible to approach a 100% yield of Synthetic product consisting of only one optical isomer, An example of the utilization of such a process is found in the production of pantothenic acid and its salts, In this process the mixture of D- and L-2-hydroxy-3,3-butyrolactones are separated. The D-lactone is condensed with the salt of beta-alanine to give the biologically active salt of pantothenic acid, The remaining L-lactone is racemized and recycled. 

Actually, coordination complexes of different metal salts of DBTA with hydroxycarboxylic acid esters, hydroxycarboxylic acids and alcohols as well as host-guest complexes of DBTA with chiral phosphine oxides and racemic alcohols can be prepared and used for separation of optical isomers. In the next subchapters theoretical and practical aspects of these recent resolution processes are summarised. 

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