4-Aza-7,9-dideazaadenosine, a new cytotoxic synthetic C-nucleoside analogue of adenosine

Article abstract of DOI:10.1016/S0040-4039(00)73494-0

The first synthesis of 10, the pyrrolo[2,1-f][1,2,4]triazine C-nucleoside congener of adenosine is described. The key intermediate ribofuranosyl pyrrole 4 is obtained by the direct C-ribosylation of pyrrolemagnesiumbromide with 2,3,5-tri-O-benzyl ribose followed by an acid-catalyzed dehydration. Vilsmeier formylation of 4 followed by N-amination and CHO -> CN conversion affords N-amino nitrile intermediate 7 which can be cyclized with formamidine acetate to the blocked title compound 9. Hydrogenolytic debenzylation completes the synthesis. In vitro growth inhibitory activities of 10 against leukemic cell lines (0.8 - 15 nM) are comparable to those of 9- deazaadenosine.