Triazolo nucleosides, synthesis

Recent advances on diverse and potent biological profiles of 1,2,3-triazolo-nucleosides along with emerging application of cHck chemistry in their synthesis and their perspectives have been reviewed [87]. In the article, the work is primarily addressed to antiviral, antimicrobial, and anticancer potency of these... 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

In contrast to nucleophilic additions to ketoses, which very often lead to diastereoisomeric products, additions to ketonucleosides have been found to be highly stereoselective, permitting ready synthesis of amino-, epimino-, triazolo-, and other rare-sugar nucleosides. 

The synthesis of the nucleoside 594 was performed by the reaction of the hydrazino derivatives 593 with acetic anhydride at room temperature. Deacetylation of 594 gave (2-deoxy-/3-D-ribofuranosyl)triazolopyrimidine (595). Reaction of 593 with acetic formic anhydride in dry pyridine followed by treatment with ammonia/MeOH gave the triazolo[4,3-c]pyrimi-dine nucleoside 596 (91MI4) (Scheme 118). 

The rearrangement also occurs when 2-hydrazino-5-nitropyridine is treated with cyanogen bromide and carbon disulfide to result in 2-amino-6-nitro-[l,2,4]triazolo[l,5-fljpyridine and 6-nitro-[l,2,4]triazolo[l,5-fl]pyridine-2-thiol, respectively (70JHC1019). The rearrangement has also been used (76JOC3124) for the synthesis of nucleosides of the [1,5-a] system. 

An interesting synthesis of these C-nucleosides utilized the easily accessible 5-(j3-D-ribofuranosyl)tetrazoles 235 as masked C-glycosyl-diazometh-ane. Reacting 235 with 2-chloro-3-nitropyridine gave a mixture of 1,2,4-triazolo[4,3-fl]pyridin-3-yl (236) and l,2,4-triazolo[l,5-a]pyridin-2-yl (237) C-nucleosides. The latter (237) resulted from thermally induced Dimroth-like rearrangement of the former (236) (86MI9) (Scheme 70). Compounds 236 and 237 possess considerable cytotoxic effect (86MI9). 

C. W. Smith, R. W. Sidwell, R. K. Robins, and R. L. Tolman, Azapurine nucleosides. 2. Synthesis and antiviral activity of 7-amino-3-a-D-arabinofuranosyl-v-triazolo[4,5-J pyrimidine and related nucleosides, J. Med. Chem., 15 (1972) 883-887. 

The 1,2,4-triazole (1,2,4-T) moiety was a key component in various potentially bioactive agents whose synthesis was reported in 1997. Thus, syntheses of analogs of the fungicides flusilazole (103) and tebuconazole (104) <97HCA706>, C-nucleosidic l-(j-triazolo[4,3-x]azinyl-3)-substituted polyols 105 <97JHC1115> and some 5-substituted 1-methyl-IH-... 

The method has also been applied to the synthesis of 4-cyanocamphor 1399 [1064], triazolo-5-cyanomethyl-4-methoxycarbonyl-l-nucleoside 1401 [1065], and (2R)-benzyl 2-[N-(2 -N-acetyl-l -a-0-allyl-4, 6 -0-acetylmuramyl)amino]-4-cyanobu-tanoate 1400 [1066] from their corresponding carboxamides. 

The combination of CuAAC and RuAAC offers the possibility of synthesizing triazoles with diverse residues and facilitates the alternation of the regioselectivity. As such, a broad spectrum of substrates is available and used, for example, in the derivatizion of nucleosides through the synthesis of triazole analogs. AgrofogUo et alJ° synthesized a small library of 1,4- and 1,5-disubstituted triazolo derivatives and compared the yielded ratio under Cu(I)- as well as Ru(II)-catalysis (with microwave irradiation) (Scheme 9.7). 

Parmenopoulou et al reported the synthesis of triazole pyrimidine nucleosides (20). The triazolo group between the sugar and the base has an important role in efficient inhibition of Ribonuclease A. 

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