engleski

Synthesis of Novel Quaternary Mannose Conjugates

Pyridinium based oximes are very useful compounds for reactivating acetylcholinesterase inhibited by toxic organophosphorus compunds. To further improve the quality of antidotes for organophosphorus poisoning, oxime reactivators were linked also to the sugar moieties.1 Sugar group bound to the oxime derivative resulted in new, desirable characteristics: the antidote retained longer in the blood circulation, subsequently the bioavailability of the antidote increased. Glycoconjugates had lower toxicity than the non-sugar analogs ; and some even displayed higher antidotal potential.1-3 A series of novel, quaternary pyridine-4-aldoxime and imidazole-2-aldoxime derivatives having a mannose conjugated to the heterocyclic ring have been prepared. The sugar residue was attached directly or through ethano or propano bivalent bridge respectively between the anomeric hydroxyl group of the monosaccharide and the nitrogen atom of the heterocyclic moiety. Several synthetic routes were investigated and the best approaches for the preparation of compounds were determined. Quaternization of 2- and 3-bromoalkyl--D- mannopyranosides with appropriate heterocyclic aldoximes resulted in the desired quaternary mannoconjugates. Structures of compounds were deduced from IR, one- (1H, 13C broadband decoupling and APT) and two-dimensional NMR (H, H-COSY, NOESY and HETCOR) spectra. Furthermore, structural requirements of the new compounds within the enzyme active site will be discussed.

Pyridinium based oximes ; Quaternary Mannose Conjugates

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