Nucleoside analog synthesis, 1,2,4-triazole

Kanishchev OS, Gudz GP, Shermolovich YG, Nesterova NV, Zagorodnya SD, Golovan AV (2011) Synthesis and biological activity of the nucleoside analogs based on polyfluoroalkyl-substituted 1,2,3-triazoles. Nucleosides Nucleotides Nucleic Adds 30 768-783... 

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-... 

A number of -acyl- and thioureido-derivatives of 3 -amino-3 -deoxythymidine have been prepared. 1 0 Michael addition of phthalimide to enal (81) was used in the synthesis of the 3 -amino-2 ,3 -dideoxyhexo-furanose nucleosides (82) (all four isomers, R=H, Me, halogen),191 and a similar enal prepared by mercuric-ion catalysed hydrolysis of L-rhamnal was used in the same way to make the L-acosaminyl nucleoside (83) and its -anomer, and the L-ristosaminyl systems (epimers at C-3 ). 2 Michael addition of 1,2,4-triazole to (81) led, after base-sugar condensation, to the triazolyl-substituted nucleosides (84, B=T, U), together with the analogous hexopyranose systems. 93 xhe imidazolyl nucleosides (85) can be made by reaction of 3 -amino-3 -deoxythymidine with l,4-dinitroimidazoles, 9 whilst the unsaturated imidazole nucleoside (87) was made by treating the phenylselenone (86) (see Section 6) with imidazole. 195... 

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). 

Ring-closing metathesis (RCM) reaction, which is one of the most powerful methods for the formation of small-sized rings or cyclopentenol ring [100, 101], was successfully applied in the synthesis of chiral cyclopentenol, as the key intermediate of carbocyclic nucleosides. Interestingly, the 1,2,3-triazole NPA analog... 

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