NMR Studies of Pyrimidinic Nucleosides Derived from 2,3‐dideoxy‐d‐ribose with Inhibitory Activity on LINE‐1 Mobility

Pyrimidine nucleoside analogues possess a high pharmacological interest. They show a highly useful antiviral activity against VIH, hepatitis B virus, and anticancer activity and are currently used for the treatment of these diseases. Given its importance, many scientists have modified the structure of these nucleoside analogues seeking to improve their properties, target specificity, efficacy, and to decrease its toxicity. As a consequence of this research, some analogues have been described with improved properties, among which are nucleosides derived from 2,3‐dideoxy‐D‐ribose such as Zidovudine (AZT), Didanosine (ddI), and Zalcitabine (ddC). Many researchers have also studied the NMRs spectra of these compounds. Particularly, they have described the influence of the anomeric configuration on the H and C NMR signals in compounds like, for example, adenosine nucleosides or in isonucleosides. As part of our research in the inhibition of transposable element such as LINE‐1, we have synthesized (Scheme 1) 18 nucleoside analogues of 2′,3′‐ dideoxyribonucleosidic nature (compounds 1–18, Figure 1) as well as their corresponding precursors (compounds 19–36, Figure 2) and assayed 1–18 against mammalian LINE‐1 retrotransposition with very interesting and promising results. While some of these compounds have already been describe in the literature (vide infra), others have been recently synthesize by us, and their minimal NMR data described in Reference 10. Here in this work, we describe the complete H and C signals assignment of these 36 nucleosides having pyrimidine, 5‐ aza‐pyrimidine, and 6‐aza‐pyrimidine bases with 2,3‐ dideoxy‐D‐ribose, both 5′‐O‐protected and unprotected (1–36), by means of its 2‐D spectra as well as 1D‐NOE experiments. In addition, and as previously reported by Okabe and Lin, we show a pattern in the H chemical shifts that allows the assignment of the α‐ and β‐ anomeric configuration based on 1‐D H NMR and without the need of further and more specific NMR experiments.