Carbon-13 nuclear magnetic resonance of 5-substituted uracils

Abstract

13C chemical shifts and Jc,h coupling constants are reported for 17 5-substituted uracils. Overall, the chemical shifts at C-5 and C-6 of the 5-substituted uracils exhibit no obvious correlation with substituent electronegativity. Instead, when the 5-substituted uracils are considered as trisubstituted ethylenes, the chemical shift data are shown to be rationalized in terms of the ability of the C-5 substituent to behave as a mesomeric acceptor or donor. It is also demonstrated that the correlation of the chemical shifts at C-6 can be used to identify two categories of 5-substituted uracils whose parent deoxynucleotide derivatives are inhibitors of the enzyme, thymidylate synthetase. It is suggested that 13C nmr spectroscopy is a potentially useful tool for predicting the effectiveness of certain modified substrates as enzymatic inhibitors.Uracil and certain of its 5-substituted analogs are involved in a number of biochemically significant roles (i.e., constituents of RNA and DNA) in all(1) Presented in part at the 162nd National Meeting of the American

Pyrimidine Nucleosides in Solution

“…The N-3, N-5 and N-6 substituted uridines and cytidines included in our present study shown 6(H-6) and 6(H-5) variations which closely parallel the substituent effects observed in the bases. The following upfield and downfield shifts of 6(H-6), relative to the unsubstituted nucleosides, are observed upon C-5 substitution : produced by base substitution reflect electron density changes originating in the C(5) = C(6) half of the pyrimidine itself, in accord with theoretical considerations, I3C nuclear magnetic resonance [34] and photoelectron spectroscopic measurements [35], which agree that uracil is not an aromatic system but that C(5)=C(6) must be regarded as a substituted ethylene or enamine unit. The nucleosides derived from methylated or halogenated uracil and cytosine may then be treated together with unsubstituted uridines and cytidines in the following discussion.…”

Chemical Constituents of the Style of Zea mays L. with Glycation Inhibitory Activity

“…Compounds 2-16 were identified as lumichrome (2), 5) chrysoeriol (3), 6) genistein (4), 7) adenosine (5), 8) guanosine (6), 9) uracil (7), 10) acetovanillone (8), 11) vanillin (9), 11) vanillic acid (10), 12) 6-methoxy-benzoxazolinone (11), 13) stigmast-4-en-3-one (12), 14) b-sitosterol (13), 15) stigmasterol (14), 16) stigmastanone (15), 17) and 7a-hydroxysitosterol (16) 18) based on comparison of their NMR spectral data with published spectral data.…”

Ultraviolet photoelectron studies of 5-trifluoromethyluracil: Electronic susceptibility of substituted uracils to nucleophilic attack

“…The calculations predict that almost 90% of the difference in the u + H electron density at the 6 position that occurs between uracil and 5-fluorouracil arises from the difference in electron density of the orbital. Table I also contains chemical shift data from CI3 N M R studies of the C(6) atom in uracil, thymine, 5-fluorouracil, and CF3U [43]. As the magnitude of the chemical shift decreases, the electron shielding at the C(6) atom is expected to decrease.…”

“…In a preliminary attempt to predict the relative susceptibility of uracil and substituted uracils to nucleophilic attack the magnitude of the total electron density at the 6 position has been considered [43]. From this point of view the INDO calculations and the N M R results predict that the susceptibility to nucleophilic attack of the C(6) atom in the molecules studied increases in the order 5-fluorouracil < thymine < uracil < CF,U.…”