C-nucleoside studies. Part 18. The synthesis of C-Nucleoside analogues of the antiviral agent (S)-9-(2,3-Dihydroxypropyl)adenine

Abstract

1-Methylsulphonyl-3-(1-O-methylsulphonyl-2,3-O-isopropylidene-D-erythro-trihydroxypropyl)-pyrazole (22), available in 56% overall yield from 1,2:5,6-di-O-isopropylidene-3-O-p-tolylsulphonyl-α-D-allofuranose (15), was treated with sodium borohydride to give 3(5)-[(S)-2,3-O-isopropylidene-dihydroxypropyl]pyrazole (23) in 90% yield. This was elaborated into 4-amino-3(5)-cyano-5(3)-[(S)-2,3-di-O-acetyldihydroxypropyl] pyrazole (30), which on treatment with formamidine acetate in refluxing ethanol, followed by sodium methoxide in methanol, gave 7-amino-3-[(S)-2,3-dihydroxy-propyl] pyrazolo[4,3-d]pyrimidine (6), a C-nucleoside analogue of the potent antiviral agent (S)-9-(2,3-dihydroxypropyl)adenine (3). Treatment of (6) with nitrous acid formed 3-[(S)-2,3-dihydroxy-propyl]pyrazolo[4,3-d]pyrimidin-7(6H)-one (7), an analogue of (3) containing the chromophore of formycin B.

Treatment of (30) with nitrous acid, basification, and photolysis of the resultant diazopyrazole in aqueous acetone yielded 3(5)-cyano-5(3)-[(S)-2,3-di-O-acetyldihydroxypropyl]-4-hydroxypyrazole (33) in 67% yield. Two further steps gave the pyrazofurin analogue 5(3)-carbamoyl-3(5)-[(S)-2,3-dihydroxypropyl]-4-hydroxypyrazole (8).