Triazine C-Nucleosides

4-Triazine Homo C-Nucleosides 1. l,2,4-Triazin-6-yl Homo C-Nucleosides 

4-triazine homo C-nucleosides prepared so far are the 1,2,4-triazin-6-yl type. Acid-catalyzed dehydrative cyclization products of the polyhydroxyalkyl chains of 6-(alditol-l-yl)l,2,4-triazines (1065) (Section XXX,D) were first assigned the corresponding 6-()3-glycofuranosyl)-l,2,4- 

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A. PYRAZOLO[l,5-a]l,3,5-TRIAZINE C-NUCLEOSIDES 1. Pyrazolo[l,5-a]l,3,5-triazin-8-yl C-Nucleosides... 

The most commonly used strategy for the synthesis of this class of C-nucleosides was the annulation of the 1,3,5-triazine ring onto suitably substituted pyrazol-4-yl C-nucleosides. Thus, the C-nucleosides 836, related to adenosine and formycin, was prepared by reacting the 3-aminopyrazol-... 

The acyclo C-nucleosides 850-852 were synthesized by reactions that involved the annulation of their 1,3,5-triazine rings onto the pyrazol-4-yl acyclo C-nucleosides 848 and 849, as shown in Scheme 221 (88JOC2413). 

Some N-glycosides have been synthesized as nucleoside analogues by Vilarrasa and co-workers <1996TL901>, the result is shown in Scheme 8. The starting compound, [l,2,4]triazolo[5,l-c][l,2,4]triazine-4(l//)-one 54, was reacted with tri-0-benzoyl-/3-diribofuranosyl bromide under two different reaction conditions. In the presence of silver triflate at low temperature, the zwitterionic 2-substituted compound 55 was obtained, whereas under reflux conditions in acetonitrile the neutral 1-substituted compound 56 was formed. 

Very few compounds containing the 1,2,4-triazine moiety are found as natural materials, such as the pyrimido[5,4-c]-1,2,4-triazines, fervenulin (2),265 reumycin (3),265 toxoflavin (4) and MSD-92 (5).441 A large number of synthetic 1,2,4-triazines have biological activity and have been used for various purposes. Thus, 1,2,4-triazines can be considered as azapyrimidines and thus a large number of 6-azapyrimidine nucleotides and nucleosides have been prepared and their properties studied intensively, for example 6-azauracil (6), 6-azathymine(7), 6-azacytosine (8), 6-azauridine (9),442 and 6-azacytidine (10).443... 

Condensation methods have been used to make P-D-gluco- and p-D-galacto-pyranosyl nucleosides of some condensed pyridinethiones and hydantoins with naphthylmethylene substituents at C-5, and glucopyranosyl derivatives of 4-amino-1,2,4-triazin-5-on-3-thiones have been described. When the acyclic amine 14 was treated with (EtO)2CHOAc, 7-(P-D-glucopyranosyl)theophylline (15) was obtained, and the analogous a-L-arabinopyranosyl compound was similarly prepared. " ... 

Examples of synthesis of trifluoromethyl-substituted 1,2,4-triazines by transformation of 3,6-bis(trifluoromethyl)-l,2,4,5-tetrazine 49 ring are presented at Scheme 20. The anomeric C-glycosyl precursors 50, functionalized by an imidate group and appropriate for C-nucleoside synthesis were utilized as heterodienophiles in a Diels-Alder reaction with inverse electron demand to yield the 0-benzyl protected 5-( 3-D-ribofuranozyl)- and 5-(a-D-ribofuranosyl)-1,2,4-triazines 51 (Scheme 20) [30]. 

There have been many reports of syntheses of deoxy nucleosides by standard sugar-base condensation reactions. These include 5 -deoxy-ribo nucleosides and 5 -mono- or 5",5-di-deuterated analogues, as well as derivatives of 5-deoxy-D-xylose and 5-deoxy-D-glucose, 5-alkylated thymidine derivatives, 2 -deoxy-6-methyl-5-azacytidine and its a-anomer, the thymidine analogue 4-(2-deoxy-B-D-erythro-pento-furanosyl)-6-methyl-l,2,4-triazine 3(HH)-one-1-oxide, 6-aza-3-deaza analogues of 2 -deoxy-cytidine and 2 -deoxyuridine,3 -deoxycytidine from a 3-deoxy-ribofuranose obtained from a fermentation broth producing the 3 -deoxy nucleoside antibiotic, cordycepin, 4-deoxy-DL-threo-pentopyranosyl pyrimidine nucleosides, and 5 -C-methyluridines derived from 6-deoxy-D-allose and 6-deoxy-D-talose. A range... 

Pyridazine C-nucleosides have been made by cyclizations of tetrazines and ribofuranosyl alkynes, as in the case of 109 and 110, which gave 111 after deprotection. 1,2,4-Triazines have been similarly prepared by cycloadditions to ribofuranosyl imidates use of 109 gave 112. Pyrazolo[l,5-a]pyrimidine C-nucleosides such as 113 have been prepared by interaction of 3-aminopyrazole with a previously-described intermediate. ... 

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