Design and Synthesis of a New Fluorescent Tricyclic Nucleoside, 3-.beta.-D-Ribofuranosylpyrazolo[3,2-i]purine

The novel nucleoside, 3-β-D-ribofurmosylpyrazolo[3,2-i]purine, has been prepared in seven steps from a fully protected 6-chloropurine derivative including a one-step reaction for the preparation of an ethyl 3-β-D-ribofuranosylpyrazolo[3,2-i] purine derivative from 6-enamino purine and hydrazine. The mechanism for the preparation of 9-ethyl-substituted pyrazolo[3,2-i]purines was elucidated. First, the hydrazino moiety of 6-enamino purine attacks at the C-6 carbon of the purine ring to give a spiro intermediate; this is followed by ring opening and cyclization. The new tricyclic nucleoside exhibited stronger fluorescence than that of 1,N 6 -ethenoadenosine. Also, the compound and the 9-bromo-substituted pyrazolo[3,2-i]purine nucleoside showed cyctotoxic activities against human leukemia CCRF-HSB-2 cells in culture