ASYMMETRIC REDUCTION IN A CHIRAL REACTION FIELD

The approach using cyclodextrin as a binding site has also been developed. Cyclodextrins are widely utilized in biomimetic chemistry as simple models for an enzyme because they have the ability to form inclusion complexes with a variety of molecules and because they have catalytic activity toward some reactions. Kojima et al. (1980, 1981) reported the acceleration in the reduction of ninhydrin and some dyes by a 1,4-dihydronicotinamide attached to 3 Cyclodextrin. Saturation kinetics similar to enzymatic reactions were observed here, which indicates that the reduction proceeds through a complex. Since the cavity of the cyclodextrin molecule has a chiral environment due to the asymmetry of D-glucose units, these chiralities are expected to be effective for the induction of asymmetry into the substrate. Asymmetric reduction with NAD(P)H models of this type, however, has not been reported. Asymmetric reduction by a 1,4-dihydronicotinamide derivative took place in an aqueous solution of cyclodextrin (Baba et al. 1978), although the optical yield from the reduction was quite low. Trifluoromethyl aryl ketones were reduced by PNAH in 1.1 to 5.8 % e.e. in the presence of 3-cyclodextrin. Sodium borohydride works as well (Table 18). In addition to cyclodextrin, Baba et al. also found that the asymmetric reductions can be accomplished in the presence of bovine serum albumin (BSA) which is a carrier protein in plasma. 

The idea of using a protein as a chiral source originates from the work by Akabori et al. (1956) who tried an asymmetric reduction of acetoximes from benzoylformate and a-ketoglutarate by means of hydrogenation catalyzed by palladium on silk fibroin. Reduced products were obtained in 30 and 7 % optical yields, respectively. 

Another successful result in this field is the reduction of olefins under the catalysis of rhodium ligated by a derivative of biotin (Wilson and Whitesides 1978). The reduction was carried out 

As shown in Table 18, trifluoromethyl aryl ketones were reduced in 22.3-46.6 % e.e. by PNAH and 15.6-38.8 % e.e. by sodium borohydride in 1.5-1.7 mM solution of BSA. The degree of asymmetric induction was rather high in comparison with those from the reactions with cyclodextrin, which suggests the possibility that such a simple protein as BSA can provide a chiral reaction field, as an enzyme does. As already mentioned some proteins have a similar (or sometimes greater) affinity toward a molecule in the ground state in comparison with an enzyme. The difference between these two proteins in different classes is the affinity toward a transition state. The enzyme has to bind the transition state more strongly than the ground state. 

Asymmetric reductions of other aromatic ketones by sodium boro- 

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