Stereoselective facile synthesis of 2′-spiro pyrimidine pyranonucleosides via their key intermediate 2′-C-cyano analogues. Evaluation of their bioactivity

Abstract

A novel series of 2′-spiro pyrimidine pyranonucleosides has been designed and synthesized. Their precursors, 2′-C-cyano nucleosides 5a,b and 6a,b, were obtained by subjecting 1a,b to the sequence of selective protection of the primary hydroxyl group, acetalation, oxidation, and finally treatment with sodium cyanide. Deoxygenation at the 2′-position of cyanohydrins 5a,b or 6a,b led to the 2′-deoxy derivatives 9a,b. Fully deprotection of 5a,b, 6a,b, and 9a,b gave the desired 2′-C-cyano 7a,b, 8a,b, and 2′-C-cyano-2′-deoxy pyranonucleosides 10a,b, respectively. Mesylation of the corresponding cyanohydrins 5a,b and 6a,b afforded compounds 11a,b and 12a,b which after base treatment and subsequent deprotection furnished the spiro nucleosides 15a,b and 16a. The new analogues were evaluated for their potential cytostatic activities in cell culture.