C-nucleoside studies. Part 22. cine-Substitution in 1,4-dinitropyrazoles: further model studies, an improved synthesis of formycin and pyrazofurin and the synthesis of some 3(5)-alkylsulphonyl-4-amino-5(3)-β-D-ribofuranosylpyrazoles

Abstract

Reaction of 3-methyl-1,4-dinitropyrazole 6 with ethyl 2-mercaptoacetate gave, by cine-substitution, ethyl [5(3)-methyl -4-nitropyrazol-3(5)-ylthio]acetate 8, which could be oxidised to the corresponding sulphoxide 11 or sulphone 12. Reduction and cyclisation of 8 and 12 gave respectively, 3-methyl-1,6-dihydropyrazolo[3,4-b]-1,4-thiazin-5(4H)-one 14 and the 5,7,7-trioxo analogue 15. Similarly treatment of 6 with glycine ethyl ester and sarcosine ethyl ester gave respectively ethyl 3(5)-methyl-4-nitropyrazol-5(3)-ylaminoacetate 16, and its N-methyl analogue 17; cyclisation of 17 gave 3,7-dimethyl-6,7-dihydro-1H-pyrazoeo[3,4-b] pyrazin-5(4H)-one 18. Reaction of 6 with various stabilized carbanions gave rise to a number of 3(5)-methyl-4-nitro-5(3)(2-oxoalkyl)pyrazoles.

3(5)-(2,3,5-Tri-O-benzyl-β-D-ribofuranosyl)pyrazole 1 was subjected to transfer hydrogenation followed by acetylation, to give 1-acetyl-3-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole 23 in 95% yield. Treatment of 23 with ammonium nitrate and trifluoroacetic anhydride in trifluoroacetic acid gave 1,4-dinitro-3-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)pyrazole 2(95%). This sequence gives a much improved route to formycin 4 and pyrazofurin 5 as compared to the previously-reported route involving 1 and 2 as intermediates.

cine-Substitution of 2 with sulphur nucleophiles, and subsequent manipulation led to the synthesis of 4-amino-3(5)-methylsulphonyl-5(3)-(β-D-ribofuranosyl)pyrazole 29 and 4-amino-3(5)-[(carbamoyl)methyl] sulphonyl-5(3)-(β-D-ribofuranosyl)pyrazole 33.