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-nucleosides are reported. Treatment of pyranulose glycoside with aminoguanidine in acetic acid gave the corresponding semicarbazone in 96% yield. The ring transformation of the semicarbazone in dioxane afforded a 51% yield of 2-amino-7-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)pyrrolo[2,1-f]-[1,2,4]triazine. Vilsmeier formylation 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 hydrochloride in methanol to give aldoximes. Dehydration of aldoxime with trifluoromethanesulfonic anhydride and triethylamine in dichloromethane afforded 5-cyanopyrrolo[2,1-f][1,2,4]triazine in 44% yield. Conversion of the nitrile 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 with sodium hydroxide solution produced deprotected C-nucleosides.
Nishimura
N
N
Faculty of Pharmacy, Meijo University, Nagoya, Japan.
Kato
A
A
Maeba
I
I
D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D011741:Pyrimidine Nucleosides / Q000138:chemical synthesis*; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013237:Stereoisomerism; D014127:Toyocamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry; D014372:Tubercidin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; D011741:Pyrimidine Nucleosides; D012263:Ribonucleosides; D014227:Triazines; C005699:sangivamycin; D014127:Toyocamycin; D014372:Tubercidin