Synthesis of pyrrolo[2,1-f][1,2,4]triazine C-nucleosides. Isosteres of sangivamycin, tubercidin, and toyocamycin

Syntheses of pyrrolo[2,1-f][1,2,4]triazine C-nudeosides are reported. Treat ment of pyranulose glycoside with aminoguanidine in acetic acid gave the co rresponding semicarbazone in 96% yield. The ring transformation of the semi carbazone in dioxane afforded a 51% yield of 2-amino-7-(2,3,5-tri-O-benzoyl -beta -D-ribofuranosyl)ptrrolr[2,1-f]-[1,2,4]triazine, Vilsmeier formylatio n of the pyrrolotriazine gave the major product. 5-formylpyrrolo[2,1-f][1,2 ,4] triazine, in 69% yield. The aldehyde was treated with hydroxylamine hyd rochloride in methanol to give aldoximes. Dehydration of aldoxime with trif luoromethanesulfonic anhydride and triethylamine in dichloromethane afforde d 5-cyanopyrrolo[2,1-f][1,2,4]triazine in 44% yield. Conversion of the nitr ile to the deprotected amide, 2-amino-7-(beta -D-ribofuranosyl)pyrrolo[2,1- f][1,2,4]triazine-5-carboxamide, was accomplished in 96% yield on treatment with 30% H2O2 in ethanol for 1 day at room temperature. Debenzoylation wit h sodium hydroxide solution produced deprotected C-nucleosides. (C) 2001 El sevier Science Ltd. All rights reserved.