Several 3,4,6-trisubstituted pyrazolo[3,4-d]
pyrimidine ribonucleosides were prepared and tested for their
biological activity. High-temperature glycosylation of 3,6-dibromoallopurinol with
1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of BF3 X OEt2, followed by ammonolysis, provided 6-amino-3-bromo-1-beta-D-ribofuranosylpyrazolo-[3,4-d]pyrimidin-4(5H)-on e. Similar glycosylation of either 3-bromo-4(5H)-oxopyrazolo [3,4-d]pyrimidin-6-yl methyl
sulfoxide or 6-amino-3-bromopyrazolo [3,4-d]pyrimidin-4(5H)-one, and subsequent ammonolysis, also gave 7a. The structural assignment of 7a was on the basis of spectral studies, as well as its conversion to the reported
guanosine analogue 1d. Application of this glycosylation procedure to 6-(methylthio)-4(5H)-oxopyrazolo[3,4-d]
pyrimidine-3-carboxamide gave the corresponding N-1 glycosyl derivative. Dethiation and debenzoylation of 16a provided an alternate route to the recently reported 3-carbamoylallopurinol ribonucleoside thus confirming the structural assignment of 16a and the
nucleosides derived therefrom. Oxidation of 16a and subsequent ammonolysis afforded 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]
pyrimidine-3-carboxamide. Alkaline treatment of 15a gave
6-azacadeguomycin. Acetylation of 15a, followed by
dehydration with
phosgene, provided the versatile intermediate 6-amino-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-4(5H)-oxopyrazolo [3, 4-d]
pyrimidine-3-carbonitrile. Deacetylation of 19 gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]
pyrimidine-3-carbonitrile. Reaction of 19 with H2S gave 6-amino-1-beta-D-ribofuranosyl-4(5H)-oxopyrazolo[3, 4-d]
pyrimidine-3-thiocarboxamide. All of these compounds were tested in vitro against certain viruses and
tumor cells. Among these compounds, the
guanosine analogues 7a and 20a showed significant activity against
measles in vitro and were found to exhibit moderate antitumor activity in vitro against L1210 and
P388 leukemia.
6-Azacadeguomycin and all other compounds were inactive against the viruses and
tumor cells tested in vitro.