Synthesis and cytotoxic evaluation of apioarabinofuranosyl pyrimidines

Abstract

In view of the potent anticancer activity of the D-arabino-configured cytosine nucleoside (ara-C), apioarabinofuranosyl pyrimidine nucleosides were designed and synthesized from D-ribose as starting material. The synthetic strategy signifies that tosylation followed by in situ cyclization, one-pot controlled oxidative cleavage and acetylation by Pb (OAc) 4 , stereoselective nucleobase condensation, inversion of hydroxyl group and uracil group converted to cytosine as the key steps. Synthesized apioarabinofuranosyl pyrimidine nucleosides were tested using breast, colon, and ovarian cancer cell lines. However, only compound 19a, 19b, and 22b have a moderate growth-suppressive effect against the luminal A breast cancer cell line MCF7. K E Y W O R D S 2, 2 0 -anhyrouridine, apioarabinofurnosyl pyrimidines, apio nucleosides, cytotoxic activity, D-ribose, Vorbrüggen base condensation

Current Strategies on the Enantioselective Synthesis of Modified Nucleosides

“…All these modifications were pursued to get better and better therapeutically useful compounds. [13][14][15][16][17] Most of these modifications have been able to solve the inherent challenge associated with unnatural nucleosides, viz to be exactly mimic like a natural nucleoside by a cellular or viral enzyme and should be sufficiently stable to perform their job. 18 Carbocyclic and C-nucleosides have also been developed to slow down the glycosidic cleavage by phosphorylases and hydrolases, which are a few potential metabolization pathways that degrade the modified nucleoside.…”

“…All these modifications were pursued to obtain more therapeutically useful compounds. 13 14 15 16 17 Most of these modifications have been able to solve the inherent challenges associated with unnatural nucleosides, i.e., to exactly mimic a natural nucleoside for recognition by a cellular or viral enzyme and to be sufficiently stable to perform their job. 18…”