ABSTRACT
The title compounds, variously protected 5'-uridine derivatives connected with 1-thiosugar with thio-phosphoesters fragment (17-22) were synthesized in sequence of reactions: phosphitylation--reaction of 5'-hydroxyl group of selectively protected nucleoside with a phosphitylating agent (N,N-diisopropyl chlorophosphoamidite), connection an phosphoroamidites with 2-bromoethanol or 3-bromopropanol and secondary oxidation with sulfur presence and finally condensation reaction of obtained products with 1-thiosugar. Received glycoconjugates (17-22) had a structure which mimic to structure of natural glycosyltransferases substrates.
Subject(s)
Enzyme Inhibitors/chemical synthesis , Glycoconjugates/chemical synthesis , Glycosyltransferases/antagonists & inhibitors , Uridine/chemical synthesis , Enzyme Inhibitors/metabolism , Enzyme Inhibitors/pharmacology , Glycoconjugates/metabolism , Glycoconjugates/pharmacology , Glycosyltransferases/metabolism , Magnetic Resonance Spectroscopy , Molecular Structure , Oxidation-Reduction , Structure-Activity Relationship , Substrate Specificity , Uridine/analogs & derivatives , Uridine/metabolism , Uridine/pharmacologyABSTRACT
5-Nitro-2-pyridyl-1-thioglucosides were used in synthesis of complex uridine derivatives (13-16) in two different sequences of reactions. In one route, the first step was glycosylation of selectively protected 5-nitro-2-pyridyl-1-thioglucoside 1 with two different glycosyl donors (5 or 6), next, the nitro group in aglycone of obtained disaccharides 7 or 8 was reduced and then obtained products 9 or 10 were condensed with uridine derivatives 3 or 4 using DMT-MM as condensing agent under microwave irradiation. In the second route, condensation and glycosylation reactions were applied in reverse order. As it turned up, a sequence of reactions affected the yield of final glycoconjugates 13-16 and depended on the type of uridine derivatives used.
