Synthesis of a Triazole Homo-C-nucleoside

Article abstract of DOI:10.1021/jo00330a004

The present paper describes a totally synthetic triazole homo-C-nucleoside.One sequence directed toward this compound started by reducing dimethyl cis-2,5-dihydrofuran-2,5-dicarboxylate to cis-2,5-bis(hydroxymethyl)-2,5-dihydrofuran with lithium borohydride.The diol could be converted to the dimesyl derivative, the ditosylate, or the cyclic sulfite.None of these compounds reacted with cyanide ion to form the 2-(cyanomethyl) derivative or to form 2,5-bis(cyanomethyl)-2,5-dihydrofuran.This first approach was put aside at this point, so that the planned conversion of the cyclic sulfite by oxidation to the corresponding cyclic sulfate was left untried.The second sequence, which was brought to completion, made use of 2,3,4,4-tetrachloro-8-oxabicyclo<3.2.1>octa-2,6-diene as the starting material.This with lithium aluminum hydride plus lithium hydride yielded 3-chloro-8-oxabicyclo<3.2.1>octa-2,6-diene, which on hydroxylation with hydrogen peroxide and osmium tetraoxide gave 3-chloro-exo-cis-6,7-dihydroxy-8-oxabicyclo<3.2.1>oct-2-ene and by combination with acetone 3-chloro-exo-cis-6,7-(isopropylidenedioxy)-8-oxabicyclo<3.2.1>oct-2-ene.Ozonolysis in methanol solution followed directly by borohydride reduction produced methyl 2,3-O-isopropylidene-β-ribofuranosylacetate.Condensation of the corresponding lactone with aminoguanidine formed 3-<(2,3-O-isopropylidene-β-ribofuranosyl)methyl>-5-amino-1,2,4-triazole, and finally acid hydrolysis removed the protective isopropylidene group and yielded the desired homo-C-nucleoside, 3-(β-ribofuranosylmethyl)-5-amino-1,2,4-triazole hydrochloride.Several derivatives of the above-mentioned lactone carrying different functions on the carbon next to the carbonylgroup were also prepared.