1,2,4-Triazole oligonucleotide synthesis

Reese CB, Ubasawa A. Namre of side-reactions in oligonucleotide synthesis involving arenesulphonyl derivatives of 3-nitro-1,2,4-triazole and related condensing agents. Nucleic Acids Symp. Ser. 1980 (7) 5-21. 

Although (1) has not been used in solid-phase oligonucleotide synthesis, another more stable arylsulfonyl derivative, l-(mesityl-sulfonyl)-3-nitro-l,2,4-triazole (MSNT), is commonly used in that strategy by the phosphotriester approach. ... 

C. B. Reese and A. Ubasawa (1980), Reaction between l-arenesulfonyl-3-nitro-l, 2,4-triazoles and nucleoside base residues. Elucidation of the nature of side-reactions during oligonucleotide synthesis. Tetrahedron Lett. pp. 2265-2268. 

Oligonucleotide Synthesis. Sulfonyl derivatives of 1,2,4-triazole, e.g. (1), are used as efficient coupling reagents in oligonucleotide synthesis by the phosphotriester method. A nitro derivative (2) allows esterification of amino acids onto hydroxymethyl... 

The most widespread use of 1,2,4-triazole continues to be as a catalyst for the transfer of acyl groups, phosphoryl groups, and phosphite groups. Its greatest utility has been in the various methods of oligonucleotide synthesis, e.g., the phospho-ramidite method, //-phosphonate method, and phosphotriester approach. Its use has been extended to the synthesis of phos-phorothioates (eq 6). ... 

A review on the 1,2,3-triazole formation via 1,3-dipolar cycloaddition of acetylenes with azides under mild conditions has been published <03H(60)1225>. The synthesis of a benzotriazole azo dye phosphoramidite and the subsequent use in solid phase synthesis of oligonucleotides has been reported <03TL1339>. The chemical reactivity of [l,2,3]triazolo[l,5-a]- and [l,5-c]-pyrimidinium salts has been published <03T4297>. A review on the use of benzotriazole as an ideal synthetic auxiliary has been disclosed <03CEJ4586>. 

Bis(hydroxymethyl)phosphonic acid esters that incorporated thymine were employed as a backbone to prepare short oligonucleotide chains. This chain was prepared by condensation of the bis(4,4 -dimethoxytrityl) protected phosphonic acid and iV or N -(2-hydroxyethyl)thymine in the presence of l-(2-mesitylenesul-fonyl)-3-nitro-l,2,4-triazole or by an Appel reaction with or N -(2-aminoethyl)thymine (89a-h). Selective removal of one DMT-group and phos-phitylation yielded the building blocks for solid supported synthesis of the short oligomers by the phosphoramidite approach. Holy has reported the synthesis of 8-amino and 8-substituted amino derivatives of acyclic purine nucleotide analogues. The 8-amino, 8-methylamino- and 8-dimethylamino-adenine and -guanine analogues of iV-(2-phosphonomethoxyethyl) and (S)-iV-(3-hydroxy-2-phosphono-methoxy-propyl) derivatives of purines (90a-i), were prepared by... 

Treatment of methoxyphosphorodichloridite with li/-1,2,4-triazole in THF at —78 °C affords methoxyphosphorobis(triazolidite) which reacts with 5 -0-dimethoxytrityl-2 -deoxynucIeosides to give (24), which in turn affords (25) and (26) on treatment with excess A -trimethylsilyl-dimethylamine or -morpholine, respectively. This preparation of deoxynucleoside phosphoramidites avoids the use of chlorodialkyl aminomethoxyphosphines, which are unstable and difficult to prepare. Little or no 3 -3 dinucleoside phosphite is formed in this case, although if the methyl group is replaced by 2-chlorophenyl, some 3 -3 -linked by-product is found. Species of type (24)—(26) are of central importance in the phosphite method of oligonucleotide phosphotriester synthesis. 

Kumar et reported the synthesis of pyrene-modified nucleotides and their effects in secondary nucleic acid structures. Pyrene was attached to the 5 -position of thymidine (26a) or to the 2 -position of 2 -deojgairidine via a triazolomethylene linker (26b), or via a triazole linker (26c). These nucleosides were converted into their phosphoramidites and then incorporated into oligonucleotides, and analysed by thermal stability and fluorescence studies. These experiments indicated that these oligonucleotides can act as specific recognition probes. 

Kaura et al. described the synthesis and hybridization properties of oligonucleotides containing 5-(l-aiyl-l,2,3-triazol-4-yl)-2 -deo3gmridines (93). These modifications showed strong thermal affinity and binding specificity towards RNA targets, due to formation of chromophore arrays in the major groove. 

---