Synthesis of bicyclic nucleosides by ring-closing metathesis

The ring-closing metathesis method is applied in the construction of confor mationally restricted bicyclic nucleosides. From diacetone-D-glucose, the u nsaturated bicyclic carbohydrate derivative 11 is efficiently obtained thro ugh two vinyl group Grignard additions, subsequent metathesis of the double bonds, and resolution of the stereochemistry by an oxidation/reduction rea ction sequence. Two separate routes differing in the 3-O-protecting group a re compared. Thus, an additional protecting step improves the yields signif icantly. Standard conversions of 11 give the bicyclic nucleoside 22 contain ing an olefinic moiety with a high potential for further functionalisation. As examples, two simple bicyclic ribo-nucleoside analogues 4 and 5, which are restricted to the unusual South-type conformations, are synthesised.