Enzymatic synthesis chiral alcohols, kinetic resolution

Surprisingly, the introduction of the pyridine ring not only influences the velocity of the enzymatic transformations, but also induces promising stereochemical effects (Table 1). For instance, at 40% conversion (R)-phenylethanol is obtained from the pyridyl acetate 25 with 73 % ee, whereas the value for the corresponding phenylacetate is only 28%. Also, the secondary alcohol liberated from the ester 26 displays 98% ee at 40% conversion, whereas the respective phenylacetate leads to 1-phenylpropanol with 94% ee but at a conversion rate of 12% only [19,20]. These results demonstrate that the stereoselecting properties of penicillin acylase may be enhanced by appropriate engineering of the substrate. This is of particular interest since this enzyme has already been used for the kinetic resolution of various chiral alcohols [21-24], e.g. furyl alkyl carbinols [24], which are valuable precursors for the de novo synthesis, with moderate to high ee values, of carbohydrates. 

It has been demonstrated that the combination of metal-catalysed racemisation and enzymatic kinetic resolution is a powerful method for the synthesis of optically active compounds from racemic alcohols and amines. There are many metal complexes active for racemisation, but the conditions for enzymatic acylation often limit the application of the metal complexes to DKR. In the case of DKR of alcohols, complementary catalyst systems are now available for the synthesis of both (R)- and (5)-esters. Thus, (R)-esters can be obtained by the combination of an R-selective lipase, such as CAL-B or LPS, and a racemisation catalyst, whereas the use of an A-selective protease, such as subtilisin, at room temperature provides (5)-esters. The DKR of alcohols can be achieved not only for simple alcohols but also for those bearing various additional functional groups. The DKR of alcohols has also been applied to the synthesis of chiral polymers and coupled to tandem reactions, producing various polycyclic compounds. 

CHMO.. has been used in the diastereoselective oxidation of different p-hydroxy sulfides to the corresponding chiral p-hydroxy sulfoxides. Chiral p-hydroxy sulfoxides represent interesting compounds used as chiral auxiliaries in asymmetric synthesis, asymmetric ligands, or as building blocks for the synthesis of cyclic sulfides, benzoxathiepines, allylic alcohols, or leukotrienes [27]. The sulfoxidation of these substrates is a kinetic resolution, in which both the sulfide and the sulfoxide can be obtained in chiral form. Oxidation of the cyclohexyl derivative (Table 6.1, entry 2) by a semipurified preparation of in the presence of the enzymatic... 

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