Resolution integration with racemization

The integration of a catalyzed kinetic enantiomer resolution and concurrent racemization is known as a dynamic kinetic resolution (DKR). This asymmetric transformation can provide a theoretical 100% yield without any requirement for enantiomer separation. Enzymes have been used most commonly as the resolving catalysts and precious metals as the racemizing catalysts. Most examples involve racemic secondary alcohols, but an increasing number of chiral amine enzyme DKRs are being reported. Reetz, in 1996, first reported the DKR of rac-2-methylbenzylamine using Candida antarctica lipase B and vinyl acetate with palladium on carbon as the racemization catalyst [20]. The reaction was carried out at 50°C over 8 days to give the (S)-amide in 99% ee and 64% yield. Rather surpris-... 

The reaction concept with this new hydantoinase-based biocatalyst is economically highly attractive since it represents a dynamic kinetic resolution process converting a racemic hydantoin (theoretically) quantitatively into the enantiomerically pure L-enantiomer [19]. The L-hydantoinase and subsequently the L-carbamoylase hydrolyze the L-hydantoin, l-11, enantioselectively forming the desired L-amino acid, l-2. In addition, the presence of a racemase guarantees a sufficient racemiza-tion of the remaining D-hydantoin, d-11. Thus, a quantitative one-pot conversion of a racemic hydantoin into the desired optically active a-amino acid is achieved. The basic principles of this biocatalytic process in which three enzymes (hydan-toinase, carbamoylase, and racemase) are integrated is shown schematically in Fig. 9. 

The enantiomers of camphorcarboxylic and sulfonic acids are used for resolution of enantiomers from racemic chiral amines and alcohols via diastereomeric salts and esters, respectively. Europium(III)- and praseodymium(III)-chelates of hydroxy-methylenecamphor derivatives are suitable chiral shift reagents for the determination of enantiomeric purity by integration of NMR spectra, because they exchange ligands with enantiomeric substrates such as alcohols and amines, thus forming diastereomeric chelates characterized by different spectra. 

Extraction devices with parallel flow have been integrated into reaction and separation systems [24—26]. Honda etal. [26] developed a microreaction system for the optical resolution of racemic amino adds. Figure 12.7 shows a schematic of the system. The microreactor used for the enzymatic reaction is a PTFE tube (500 mm inner diameter) with immobilized acylase on the inner wall. The channel for extraction has 200 pm width, 100 jm depth and 40 mm length and the space between plates is made of glass (bottom) and silicon (top). The charmel surface of sflicon is coated with Au and octadodecyl groups. Consequently, the resulting microchannel has a hydrophilic... 

We recently used L-aminoacylase to provide the amino acids shown in Scheme 8. In these instances either the aldehydes were not available or they performed very poorly in the Erlenmeyer chemistry for enamide synthesis. These resolutions can be integrated very readily into an overall process, where the unwanted isomer can be racemized and recycled by way of treatment with acetic anhydride and racemization via the azalactone. 

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