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

Abstract

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-(alpha-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-alpha-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-alpha-D-talopyranosyl)nucleosides (15a-c). The newly synthesized compounds were evaluated for their potential antiviral and cytostatic activities in cell culture. (C) 2012 Elsevier Ltd. All rights reserved.