Proton magnetic resonance study of nucleosides, nucleotides, and dideoxynucleoside monophosphates containing a syn pyrimidine base

Abstract

Proton magnetic resonance data have been obtained for 6‐methyl‐2′‐deoxyuridine (dT*), its 3′‐ and 5′‐monophosphates, and its 3′,5′‐diphosphate, as well as for the corresponding thymine derivatives. The synthesis of the dideoxynucleoside monophosphates—d(TpT), d(T*pT), d(TpT*), and d(T*pT*)—was accomplished, and spectral data were obtained for these four dimers. The data show that the 6‐methyluracil base prefers the syn conformation about the N‐glycosyl bond at the monomer and dimer levels. The presence of the syn base leads to increases in the cis couplings of the sugar ring, J1′2″ and J2′3′, which indicate a trend towards eclipsing of the substituents on the C1′‐C2′ and C2′‐C3′ fragments. This trend is discussed in terms of changes in the pseudorotational parameters which describe the pucker of the ring. The syn base destabilizes the g+ conformer about the C4′‐C5′ bond, leading to a preference for the t conformer in all dT* residues at the monomer and dimer levels. Preliminary work on the formation of cyclobutane‐type photodimers in d(T*pT) and d(T*pT*) is discussed and presented as evidence for the capability of the syn 6‐methyluracil base to form base‐stacked complexes.

A conformational study of the adducts of 2′-deoxythymidine and 2,2,6,6-tetramethyl-1,4-piperidone-N-oxyl by 1H and 13C nuclear magnetic resonance

“…That the cis couplings of dU are similar to those of 6TI and 6T2 for which a syn conformation is proposed is interesting, since in the syrl nucleoside m6dU increases are observed in J( 1'2") (8.6 Hz) and J(2'3') (8.2 Hz) (29). Such increases can be rationalized by shifts in the values of P(N) and P(S) towards to 04'-endo conformation (38). It may be that these changes in pucker, which do not accompany the syn 6TI and 6T2 bases, are characteristic of 5,6-unsaturated pyrimidine nucleosides.…”