DFT studies of new class of single-headed nucleosides derived from the D-glucaric acid

Abstract EN

The nucleoside analogues can be conveniently classified into cyclic or acyclic analogues.

The goal of this study is to anticipate the structural and electronic properties of new single-headed acyclo-C-nucleosides derived from the D-glucaric acid which are able to be in equilibrium with their corresponding cyclic forms by lactonization.

The heterocyclic moieties selected for this study are: the 1,3,4-oxadiazole-2-thione, the 1,2,4-triazole-3-thiol and the 4-amino-1,2,4-triazole-3-thiol.

Using density functional theory, the candidate nucleosides will be compared with the D-glucaric acid and its mono-lactones that are used as references.

The results indicated that incorporating of the heterocycles significantly increase the reactivity of the new nucleosides.

For the cyclic forms, a high reactivity of the molecules carrying the 6,3-lactone ring are observed in comparison with those carrying the 1,4-lactone ring.

Whereas for the acyclic forms, the substitution of the carboxylic acid group by the heterocyclic moiety in position of carbon C6 gives a greater stability to the molecules compared with the same substitution in position C1.

The results motivate theoretically the synthesis of this new class of nucleoside analogues, but it remains to find out the experimental conditions