Stereocontrolled synthesis of 4′-C-cyano and 4′-C-cyano-4′-deoxy pyrimidine pyranonucleosides as potential chemotherapeutic agents

A new series of 4′- C -cyano and 4′- C -cyano-4′-deoxy pyrimidine pyranonucleosides has been designed and synthesized. Commercially available 1,2,3,4,6-penta- O -acetyl- d -mannopyranose ( 1 ) was condensed with silylated 5-fluorouracil, uracil, and thymine, respectively to afford after deacetylation 1-(α- d -mannopyranosyl)nucleosides ( 2a–c ). Subjecting 2a–c to the sequence of specific acetalation, selective protection of the primary hydroxyl group and oxidation, the 4′-ketonucleosides 6a–c and 7c were obtained. Reaction of compounds 6a , b, and 7c with sodium cyanide and subsequent deprotection gave the target 1-(4′- C -cyano-α- d -mannopyranosyl)nucleosides 12a–c . Deoxygenation at the 4′-position of cyanohydrins 8a , b, and 11c followed by deprotection led to the desired 1-(4′- C -cyano-4′-deoxy-α- d -talopyranosyl)nucleosides ( 15a–c ). The newly synthesized compounds were evaluated for their potential antiviral and cytostatic activities in cell culture.