engleski

Tuning the Stereoselectivity of Butyrylcholinesterase

Optically active quinuclidin-3-ol is an important intermediate in the preparation of physiologically or pharmacologically active compounds. Thus, new methods for the efficient production of chiral quinuclidin-3-ols are still examined. It has been shown that stereoselectivity of hydrolyses catalysed by butyrylcholinesterase (BChE ; EC 3.1.1.8) was in favour of the (R)-enantiomers in the case of quinuclidinium benzoates.1-3 In this study racemic, (R)- and (S)- esters of quinuclidin-3-ol and propionic acid were synthesized as well as their racemic and chiral, quaternary N-benzyl and N-p-brombenzyl derivatives in order to investigate their hydrolysis by horse serum BChE. The rates of hydrolyses were monitored (HPLC) at 30 oC in 0.1 M phosphate buffer pH 7.4 (2 mM concentrations of chiral esters). Kinetic study revealed that (R)-enantiomers of tested esters are much better substrates than (S)-enantiomers. In the case of N-benzyl protected esters, the rate of hydrolysis of (R)-ester was 490 fold faster than that of (S)-ester. Introduction of bromine atom in the para position on the phenyl ring of benzyl moiety resulted in a remarkable improvement in the enantioselectivity of hydrolysis: under the same experimental conditions it was not possible to monitor the very slow reaction of (S)-N-p-brombenzyl ester. From that data it can be concluded that BChE is suitable as a biocatalyst for the resolution of racemic, N-benzyl protected quinuclidinium esters. 1. Ines Primozic, Tomica Hrenar, Srdjanka Tomic and Zlatko Meic, Journal of Physical Organic Chemistry 15 (2002) 608-614. 2. Ines Primozic, Tomica Hrenar, Srdjanka Tomic and Zlatko Meic, European Journal of Organic Chemistry (2003) 295-301. 3. Ines Primozic, Tomica Hrenar, Srdjanka Tomic and Zlatko Meic, Croatica Chemica Acta 76 (2003) 93-99.

butyrylcholinesterase; enzimic resolution; esters of quinuclidin-3-ol; hydrolysis kinetics

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