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

J. Grant Buchanan, Amir O. Jumaah, Gordon Kerr, Ratnakar R. Talekar, Richard H. Wightman

Research output: Contribution to journalArticle

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[3,4-6]-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-pyrazolo[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-ß-D-ribofuranosyl) pyrazole 1 was subjected to transfer hydrogenation followed by acetylation, to give 1-acetyl-3-(2,3,5-tri-O-acetyl-ß-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-ß-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)-(ß-D-ribofuranosyl)pyrazole 29 and 4-amino-3(5)-[(carba-moyl)methyl]sulphonyl-5(3)-(ß-D-ribofuranosyl) pyrazole 33.

Original languageEnglish
Pages (from-to)1077-1083
Number of pages7
JournalJournal of the Chemical Society, Perkin Transactions 1
Issue number5
Publication statusPublished - 1991

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