engleski

Synthesis, characterization and evaluation of 10,11-dihydrocinchonidine carbamates as potential cholinesterase inhibitors

Cinchonidine belongs to class of alkaloids found in the bark of Cinchona tree, together with cinchonine, quinine and quinidine. These alkaloids have various uses in chemistry, for example they are used as organocatalysts in asymmetric synthesis or as chiral stationary phases and chiral solvating agents in chromatographic separations. Also, they posses a wide range of biological activity such as antimalarial, antibiotic and antiparasitic. By transfer hydrogenation of cinchonidine using formic acid/ammonium formate as hydrogen donor and palladium on carbon as a catalyst 10, 11 dihydrocinchonidine was prepared and used as starting material for synthesis of his carbamate derivatives. We have prepared a series of mono- and disubstituted aliphatic (methyl, ethyl) and aromatic (phenyl) 10, 11 dihydrocinchonidine carbamates. Carbamate derivatives have been prepared by reaction of 10, 11 dihydrocinchonidine with appropriately substituted isocyanates or carbamoyl chlorides. Synthesized compounds were characterized by FT-IR, 1D and 2D 1H and 13C NMR spectroscopy. Extensive docking studies and quantum chemical calculations were used to define intermediates and transition states in the course of the carbamylation reaction as well as other possible interactions of prepared compounds within the active sites of enzymes. All prepared carbamate derivatives will be screened for their ability to inhibit human acetylcholinesterase and butyrylcholinesterase activity.

10, 11-dihydrocinchonidine ; carbamates ; docking studies

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