C-nucleoside studies. Part 9. Synthesis of 3(5)-α-D-ribofuranosyl pyrazole and related compounds

Abstract

3-~1,2:4,5-Di-O-isopropylidene-~-a/lo-l,2,3,4,5-pentahydroxypentyl)-1-(2,4-dinitrophenyl)pyrazole (8) was prepared in four steps (40% overall yield) from 2,3:5,6-di-O-isopropylidene-~-allose (4). Treatment of (8) with acetone and concentrated sulphuric acid formed a mixture of (8) and its 1,3:4,5-(12) and 2,3:4,5-di-Oisopropylidene (1 3) isomers. On treatment with methanesulphonyl chloride in pyridine, the isomer (1 3) formed an unstable methanesulphonate ester which spontaneously underwent cyclisation with loss of acetone to giveReaction of 2,3,5-tri-O-benzyl-D-ribofuranosyl chloride with 3,3-diethoxyprop-1 -ynylmagnesium bromide, and treatment of the major product with aqueous acid and hydrazine, yielded 3(5)-(2,3,5-tri-O-benzyI-a-~-ribo-furanosy1)pyrazole (25), which could be converted in 3 steps (62% overall yield) into ( 21).Treatment of (25) with boron trichloride and subsequent methanolysis produced 3(5) -cr-D-ribofuranosylpyrazole (3) in 61% yield.SINCE the discovery 2 9 3 of the C-nucleoside antibiotics formycin, formycin B, and pyrazofurin (pyrazomycin) together with its a -a n ~m e r , ~ all of which contain the pyrazole ring, there has been considerable interest in the synthesis of C-pentofuranosylpyrazoles.5~6 Previous papers in this series have described syntheses of 3(5)-