8-Aza-3-deazaguanine modification strengthens the anomeric effect and affects other conformational preferences of modified guanine nucleosides
Journal of the Chemical Society. Perkin Transactions 2 (2001)
A variable temperature-dependent 1 H NMR conformational analysis of 3 J HH coupling constants and NOE enhancements of a series of 8-aza-3-deaza modified guanine nucleosides 2 and 4-8 has been performed in DMSO-d 6 and the results compared to those for natural nucleosides dG (1) and G (3). 8-Aza-3-deaza nucleobase modification leads to the stabilization of N-type conformers by ∆∆HЊ of 3.1 kJ mol Ϫ1 , which has been attributed to the strengthening of the O4Ј-C1Ј-N9 anomeric effect. The
... ng of the anomeric effect of 8-aza-3deazaguanine compared to guanine is explained by the redistribution of electron density from N9 into the pyridine moiety which facilitates n O4Ј → σ* C1Ј-N9 orbital interactions. The anomeric effect of 8-aza-3-deazaguanine in 8a3d-dG (2) is approximately 19.5 kJ mol Ϫ1 with the assumption that the steric effects of nucleobases in dG (1) and 8a3d-dG (2) are comparable. 2Ј-and 3Ј-Substituents drive the N S equilibrium via their involvement in gauche effects, which are only moderately affected by the nucleobase modification. The 2Ј-OH group in ribo (4), xylo (7) and 3Ј-deoxyribo (8) counterparts, however, drives the N S equilibrium towards S by the gauche effect of the [N9-C1Ј-C2Ј-O2Ј] fragment, which has been strengthened by ∆∆HЊ of 1.8 kJ mol Ϫ1 due to 8-aza-3-deaza nucleobase modification. 2Ј-F in the arabino analogue 8a3d-FaraG (6) showed conformational preferences which are nucleobase specific and could not be attributed to the gauche effects. The larger population of γ t rotamers in 1-8 correlates with the larger population of N-type conformers.