The Chemistry of Pseudouridine. Synthesis of Pseudouridine-5'-Diphosphate^*

Glutathione-catalyzed hydrogen isotope exchange at position 5 of uridine. Model for enzymic carbon alkylation reactions of pyrimidines

“…Thus, it is likely that the GSH-catalyzed isotope exchange involves the nucleophilic addition elimination of the S H group of G S H across the 5,6-double bond of Urd. Sulfhydryl addition to the 5,6-double bond has been demonstrated by the formation of 6,5 '-cyclonucleosides from 5 '-thiouridine and its acetonide (Bannister and Kagan, 1960;Chambers and Kurkov, 1963;Reist et al, 1964) and has also been implicated in the mechanism of certain substitution reactions of 5-bromouracils (Szabo et al, 1970). Similar adduct formation between bisulfite and Urd was recently reported to occur readily in aqueous solutions (Shapiro ef al., 1970;Hayatsu et al, 1970).…”

“…This argument is supported by the finding that at equilibrium, in neutral solution, 2 0 z of 5 'thiouridine is in the adduct form (Reist ef a/., 1964), as a consequence of the intramolecular nature of the reaction. Furthermore, the equilibrium of the addition of the 5 '-SH group of the 2 ',3 '-isopropylidene derivative of 5 '-thiouridine to the 5,6-double bond is shifted further toward the formation of, the adduct, yielding a stable, crystallizable compound (Chambers and Kurkov, 1963), showing the strong influence of the molecular conformation on this equilibrium. Thus, it can be concluded that the nucleophilic addition of an enzymic SH group to the 5,6-double bond of pyrimidine nucleotides could be ~ j A direct 1,2-trans addition followed by exchange through ionization of H-5 and subsequent elimination is also compatible with the results, as was pointcd out by one of the reviewers.…”

Incorporation of oxygen-18 into nucleosides and bases

“…However, some reaction of both 5-iodouridine (forms uridine) and 5-hydroxyuridine (hydrolyzes to 5-hydroxyuridi,eandribose) in acid was observed, but the extent of degradation was less than 10% after 30 hours. The situation is different with pseudouridine which has been shown to be hydrolyzed to a mixture of a-and 0-ribofuranosides and a-and S-ribopyranosides (16,17). The total ion chromatogram from gas chromatography-mass spectrometry of the trimethylsilylated reaction mixture of pseudouridine indicated the presence of four components with one being present in large excess (>50%).…”

Identification of a Pyrrole Intermediate Which Undergoes C‐Glycosidation and Autoxidation to Yield the Final Product in Showdomycin Biosynthesis

“…Although showdomycin and 1'-epi-showdomycin were both detected as autoxidation products of 16,t his result cannot be referred to the stereochemistry of 16 or 15 without more direct evidence.T his is because C-nucleosides are known to be susceptible to epimerization at C1' under acidic conditions. [33][34][35][36]…”