ABSTRACT
A thorough study for the synthesis of 1-deazauridine is described. 3-Bromo-2,6-dimethoxy-5-(beta-D-ribofuranosyl)pyridine, a synthetic precursor for 1-deazauridine, was prepared in seven steps from 2,6-dimethoxypyridine and d-ribose via the ribonolactone approach. Subsequent demethylation was unsuccessful but led to presumable anomerization and isomerization. The effort concluded that the synthesis of 1-deazauridine remained unachieved.
Subject(s)
Pyridines/chemistry , Pyridines/chemical synthesis , Uridine/analogs & derivatives , Lactones/chemistry , Magnetic Resonance Spectroscopy , Models, Chemical , Ribose/analogs & derivatives , Ribose/chemistry , Uridine/chemical synthesis , Uridine/chemistryABSTRACT
The reactions of 6-cyano-1,3-dimethyluracil have been studied as chemical models to illustrate the mechanism for the transformation of 6-cyanouridine 5'-monophosphate (6-CN-UMP) to barbiturate ribonucleoside 5'-monophosphate (BMP) catalyzed by orotidine 5'-monophosphate decarboxylase (ODCase). The results suggest that the Asp residue in the ODCase active site plays the role of a general base in the transformation.
Subject(s)
Orotidine-5'-Phosphate Decarboxylase/metabolism , Uridine Monophosphate/analogs & derivatives , Barbiturates/chemistry , Biocatalysis , Catalytic Domain , Models, Chemical , Orotidine-5'-Phosphate Decarboxylase/chemistry , Uridine Monophosphate/biosynthesis , Uridine Monophosphate/chemistry , Uridine Monophosphate/metabolismABSTRACT
Orotidine 5'-monophosphate decarboxylase (ODCase) catalyzes an unprecedented transformation of 6- cyanouridine 5'-monophosphate (6-CN-UMP) into barbiturate nucleoside 5'-monophosphate (6-hydroxyuridine 5'-monophosphate, BMP). The reactions of 6- cyano-1,3-dimethyluracil toward various nucleophilic conditions have been studied as chemical models in order to understand the possible mechanism for the ODCase-catalyzed transformation of 6-CN-UMP.