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.