engleski

Synthesis of some b6 vitamin analogs– potential antidotes

Due to the continuous threat of chemical weapon (insecticides or nerve poisons e.g. VX, soman, sarin and tabun), the synthesis of compounds, which are able to reactivate by organophosphorus compounds inhibited cholinesterase became again very actual. Phosphorylated cholinesterase can be reactivated by the action of certain nucleophiles among them Pralidoxime, Toxogonine, TMB-4, LüH6 and H-oximes (HI-6, HLö) have proven to be the most potent. These quaternary pyridinium salts must have an oxime group in position 2 or 4 of the pyridinium ring to be used as antidotes (1, 2). Pyridoxal oxime, a derivative of B6 vitamin, meets this structural feature and was used for synthesis of three mono- and three bisquaternary salts, two of them exerting quite good reactivating potency (3, 4). Therefore the goal of this work was continuation of preparation of some pyridoxal oxime derivatives by changing the substituents in positions 2, 4 and 5 of pyridine ring, or by incorporating new group into position 6 as well as to obtain the molecule having two oxime groups in the same structure. The compounds synthesized are suitable for quaternization to obtain compounds similar to the conventional antidotes in use. Furthermore, two mono- and one bisquaternary salt of pyridoxal oxime were obtained by reaction with chloroethanol and 1, 3- dibromopropane, respectively, while the reaction with hydrogen peroxide in acetic acid yielded some novel N- oxides. The compounds obtained were characterized by means of elemental analysis, IR, MS, 1H and 13C NMR spectroscopy.

Pyridoxal oxime ; quaternary pyridinium salts ; antidotes ; cholinesterase

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