4-AZA-7,9-DIDEAZAADENOSINE, A NEW CYTOTOXIC SYNTHETIC C-NUCLEOSIDE ANALOG OF ADENOSINE

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 2 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.