8-Aza-3-deazaguanine modification strengthens the anomeric effect and affects other conformational preferences of modified guanine nucleosides

Miha Plevnik, Martin Črnugelj, Anton Štimac, Jože Kobe, Janez Plavec
2001 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
more » ... 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.
doi:10.1039/b009401n fatcat:iqbw2gnvzbgkllt4m5w5ijoroy