Comparative studies were made by the use of organosilicon compounds having a different chain length between hydroxyl group and the silicon atom [Me3Si(CH2)nOH, n = 0, 1, 2, and 3] and the corresponding carbon compounds [Me3C(CH2)nOH, n = 0, 1, and 2) as another substrate (acyl acceptor) in the enantioselective esterification of 2-(4-chlorophenoxy)propanoic acid, whose (^)-enantiomer is useful as a herbicide, with lipase OF 360 of Candida cylindracea (Fig. 1) in benzene. The effects of the silicon atom on the enzymatic reaction in connection with the distance between the hydroxyl group and the silicon atom are discussed (8). Organosilicon compounds and the carbon counterparts examined in this study, except for the case of n = 0 (trimethylsilylmethanol and 1,1-dimethylethanol), served as the substrates. In particular, trimethylsilylmethanol (n = 1) was found to be a particularly superior substrate, that is, the reaction rate was much higher than that with the corresponding carbon compound, and the enantiomeric excess of the acid remaining was also higher at about 50% conversion. In the case of conventional substrates such as the carbon analogs and linear-chain alcohols (9), a
Fig. 1. Lipase-catalyzed enantioselective esterification of 2-(4-chlorophenoxy) propanoic acid with organosilicon compounds and the corresponding carbon analogs in benzene (8). El = Si or C.
high enantioselectivity was not consistent with a high reaction rate. These results indicate that organosilicon compounds as novel substrates may solve some of the unavoidable and probably inherent problems of enantioselective reactions with conventional substrates. On the other hand, a difference was not observed between 2-trimethylsilylethanol (n = 2) and its carbon analog, 3,3-dimethylbutanol, in the enzymatic activity and enantioselectivity. Thus, the silicon atom mimicked the carbon atom for lipase in the case of 2-trimethylsilylethanol (n = 2) but made trimethylsilylmethanol (n = 1) an excellent substrate for enantioselective esterification with lipase in an organic solvent (see Notes 1 and 2). These phenomena were explained on the basis of the properties of the silicon atom, such as its lower electronegativity and larger atomic radius compared with carbon. A lower electronegativity of the silicon atom gives rise to a higher nucleophilicity of the oxygen atom of trimethylsilylmethanol (n = 1) compared with that of the corresponding carbon analog, and the hydroxyl group of trimethylsilylmethanol (n = 1) is less steri-cally hindered because of the longer bond of Si-C than that of C-C in the corresponding carbon analog (Fig. 2). Trimethylsilylmethanol (n = 1) is, therefore, more easily accessible to the acyl-enzyme intermediate and reacts as an much better acyl acceptor than the carbon analog. In the case of trimethylsilylethanol (n = 2), the favorable effect of the silicon atom previously mentioned was negligible because of the presence of a long ethylene group between the silicon atom and the hydroxyl group. Trimethylsilylethanol (n = 2) was, consequently, regarded as a substrate similar to the corresponding carbon compound by lipase. In spite of the favorable characteristics of the silicon atom, trimethylsilanol (n = 0) did not serve as a substrate of lipase, similar to the corresponding tertiary alcohol.
As far as we know, this work is the first study where the effects of the silicon atom in substrates for enzymatic reactions have been systematically discussed. Furthermore, this study demonstrated for the first time the ability of organosilicon compounds to break the limit of conventional substrates owing
Not so sterically hindered
Sterically hindered rO
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