Design and synthesis of a nucleoside and a phosphonate analogue constructed on a branched-threo-tetrofuranose skeleton

The synthesis of a novel nucleoside phosphonate constructed on a branched-threo-tetrofuranose scaffold, as a potential antiviral agent, is described. The pseudosugar moiety served as the nucleoside skeleton was produced starting from 2-butyne-1,4-diol in 10-steps. Glycosylation with the pseudosugar involved stereoselective neighboring group participation of p-anisyl group and gave the nucleoside derivative in 94% yield. After manipulating the protecting group and introduction of a methylenephosphate unit, the synthesis of the target novel cytidine phosphonate was achieved. The resulting nucleoside, a synthetic intermediate of the nucleoside phosphonate, would also be expected to serve as a useful building block for the synthesis of novel antisense/antigene derivatives.

Graphical abstractDownload full-size image