Sa. Patil et al., 4-AZA-7,9-DIDEAZAADENOSINE, A NEW CYTOTOXIC SYNTHETIC C-NUCLEOSIDE ANALOG OF ADENOSINE, Tetrahedron letters, 35(30), 1994, pp. 5339-5342
The first synthesis of 10, the pyrrolo[2,1-f][1,2,4]triazine C-nucleos
ide congener of adenosine is described. The key intermediate ribofuran
osyl pyrrole 4 is obtained by the direct C-ribosylation of pyrrolemagn
esiumbromide with 2,3,5-tri-O-benzyl ribose followed by an acid-cataly
zed dehydration. Vilsmeier formylation of 4 followed by N-amination an
d CHO --> CN conversion affords N-amino nitrile intermediate 2 which c
an be cyclized with formamidine acetate to the blocked title compound
9. Hydrogenolytic debenzylation completes the synthesis. In vitro grow
th inhibitory activities of 10 against leukemic cell lines (0.8 - 15 n
M) are comparable to those of 9-deazaadenosine.