engleski

Stereoselective biotransformations of N-benzyl protected quaternary quinuclidinium esters

In order to investigate the dependance of enzyme activity and enantioselectivity on the ester's quaternary amonium group, three diferent N-quaternary quinuclidinol propanoates were prepared. To prepare chiral esters of quinuclidin-3-ol and propanoic acid, first, racemic quinuclidin-3-yl acetate was synthesized by esterification of quinuclidin-3- ol with acetic anhydride. Resolution of the racemate with L- and D-tartaric acid, enantiomericaly pure acetates were obtained. Chiral (R)- and (S)-quinuclidin-3-ols were prepared by hydrolysis of (R)- and (S)-acetates respectively. N-benzyl derivatives were synthesized in the next step by quaternization of appropriate chiral or racemic ester with benzyl bromide, p-methylbenzyl bromide and p- nitrobenzyl bromide. The strucutures and purity of all compounds were deducted from IR, one- and two-dimensional NMR, and optical purity by optical rotation measurement. Butyrylcholinesterase (BChE) was identified, among other tested esterases, as a catalyst of choice in hydrolysis reactions of prepared quaternary esters. All compounds were then tested as substrates of serum butyrylcholinesterase (BChE ; EC 3.1.1.8). The initial rates of hydrolyses were monitored (HPLC) at 30°C in 0.1 M phosphate buffer pH=7.4 (2 mMconcentration of substrates). The preface of BChE towards (R)-enantiomers and unsubstitued N-benzyl derivatives as well as the difference in the rates of hydrolysis among enantiomers will be discussed.

syntheses ; quaternization ; resolution of enantiomers ; N-benzyl esters of quinuclidin-3-ol ; butyrylcholinesterase

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