Efficient optical resolution of 2-(4-chlorophenoxy)propanoic acid with lipase by the use of organosilicon compounds as substrate: the role of silicon atom in enzymatic recognition

Comparative studies were made of the use as acyl acceptor of organosilicon compounds [Me₃Si(CH₂)_nOH] and the corresponding carbon compounds [Me₃C(CH₂)_nOH] in the stereoselective esterification of 2-(4-chlorophenoxy)propanoic acid by the use of lipase OF 360 of Candida cylindracea in water-saturated benzene. The organosilicon compounds were effectively used as the substrates for the esterification of the d-acid enantiomer. Of the organosilicon compounds of different chain-length between the silicon atom and the hydroxyl group, trimethylsilylmethanol (n = 1) enabled the esterification reaction to be both fast and highly stereoselective, which was difficult with conventional substrates such as its carbon counterpart. On the other hand, no difference was observed between trimethylsilylethanol (n = 2) and its carbon analogue (3,3-dimethylbutanol) in the enzymatic activity and the stereoselectivity. These results indicate that the silicon atom behaved as a mimic carbon atom for lipase in the case of trimethylsilylethanol but was effective in enhancing the reactivity of trimethylsilylmethanol. The difference could be explained on the basis of the properties of silicon atom, such as its low electronegativity and big atomic radius compared with the carbon atom.