DESIGN AND SYNTHESIS OF A NEW FLUORESCENT TRICYCLIC NUCLEOSIDE, 3-BETA-D-RIBOFURANOSYLPYRAZOLO[3,2-I]PURINE

The novel nucleoside, 3-beta-D-ribofuranosylpyrazolo[3,2-i]purine, has been prepared in seven steps from a fully protected 6-chloropurine de rivative including a one-step reaction for the preparation of an ethyl 3-beta-D-ribofuranosylpyrazolo[3,2-i]purine derivative from 6-enamino purine and hydrazine. The mechanism for the preparation of 9-ethyl-su bstituted pyrazolo[3,2-i]purines was elucidated. First, the hydrazino moiety of 6-enamino purine attacks at the C-6 carbon of the purine rin g to give a spiro intermediate; this is followed by ring opening and c yclization. The new tricyclic nucleoside exhibited stronger fluorescen ce than that of 1,N6-ethenoadenosine. Also, the compound and the 9-bro mo-substituted pyrazolo[3,2-i]purine nucleoside showed cytotoxic activ ities against human leukemia CCRF-HSB-2 cells in culture.