C-nucleoside studies. Part 17. The synthesis of 3(5)-carbamoyl-5(3)-β-D ribofuranosylpyrazole (4-deoxypyrazofurin) and 4-amino-3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole

Abstract

4-Amino-3(5)-cyano-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (10) was converted into the diazopyrazole (11) by treatment with nitrous acid. On photolysis in aqueous dioxane using visible light compound (11) gave 3(5)-cyano–5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (12)[48% from (10)] which formed the corresponding amide (13)(75%) with alkaline hydrogen peroxide. Deprotection of compound (13) with methanolic ammonia afforded 3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole (4)(74%), the 4-deoxy analogue of pyrazofurin (3).

3(5)-Cyano-4-nitro-5(3)-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole (1) reacted with dihydropyran and toluene-p-sulphonic acid to give the N-tetrahydropyranyl derivative (21)(66.5%). Hydrolysis of the nitrile group of compound (21), using alkaline hydrogen peroxide, afforded the amide (22)(71%) which was deprotected to give 3(5)-carbamoyl-4-nitro-5(3)-β-D-ribofuranosylpyrazole (23)(83%). Catalytic reduction of compound (23) gave 4-amino-3(5)-carbamoyl-5(3)-β-D-ribofuranosylpyrazole (5)(83%) which could be converted into formycin B (24)(69%).