Synthesis of bitriazolyl nucleosides and unexpectedly different reactivity of azidotriazole nucleoside isomers in the Huisgen reaction

Abstract

Novel bitriazolyl nucleosides were synthesized via the Huisgen reaction, starting with 3-azidotriazole nucleoside (1). Surprisingly, its isomer, 5-azidotriazole nucleoside (1') did not yield the corresponding Huisgen reaction products efficiently because it was rapidly reduced to amine in the presence of Cu(II)-ascorbate. The significant differences between the reactivity of these two isomers in Cu(II)-ascorbate mediated reactions are mainly due to differences in their electronic properties and steric congestion as a result of different relative positions of the azido and the ribosyl moieties.

Bitriazolyl acyclonucleosides with antiviral activity against tobacco mosaic virus

“…14 Bitriazolyl acyclonucleosides 2 were formed in good to excellent yields 15 (Scheme 4, Table 1) via the copper(I)-catalyzed Huisgen reaction under similar conditions to those previously described. [6][7][8] In the case of products 2, which were obtained in yields of less than 80%, the Cu(I) catalyst loading was increased from 5% to 30%. In most cases, this improved the product yields to 90% or more.…”

“…3 In our search for novel triazole compounds with potential medicinal and agrochemical applications, [4][5][6][7][8] we discovered that bitriazolyl compounds (A in Scheme 1) as well as bitriazolyl ribonucleosides (B in Scheme 1) have promising antiviral effects on the tobacco mosaic virus (TMV), an agricultural plant virus. 7,8 It is worth noting that the two triazole rings in the bitriazolyl motif show quasi co-planarity, 7,8 which results in an expanded aromatic system. This feature may promote the binding of bitriazolyl compounds to their biological targets by providing a larger aromatic binding surface, broader scope for H-bonding and greater polarity due to the triazole structural motifs.…”

“…Bitriazolyl acyclonucleosides were synthesized using the strategy previously developed for bitriazolyl ribonucleosides, 8 namely, via the Huisgen reaction 11 between azidotriazole acyclonucleosides and various terminal alkynes, and then subjected to ammonolysis in NH 3 /MeOH (Scheme 2).…”

New functionalized mercaptoundecahydrododecaborate derivatives for potential application in boron neutron capture therapy: Synthesis, characterization and dynamic visualization in cells

“…The spectra of 12 and 14 showed the expected doubly charged negative molecular ions m/z 274.2 and m/z 433.2, respectively, in the typical 10 B/ 11 B isotopic pattern.2.1.3 Click chemistry of BSH derivatives: Though a variety of click reactions have been reported in the literature, the Huisgen 1,3-dipolar cycloaddition of azides and alkynes plays a particularly important role in organic synthesis, and has become a common coupling procedure in all chemical disciplines in recent times. Four distinct observations have drawn our attention to the possibility of applying click chemistry to the synthesis of BNCT agents: (1) This reaction is high yielding without generating offensive byproducts and requires only minimal purification; (2) The reaction proceeds in benign solvent, usually water; (3) Triazole units are heterocyclic structural motifs with considerable medicinal and agrochemical potential[39];(4) It is possible to generate a plethora of new compounds quickly and reliably, which thereby accelerates the process of drug discovery.…”

New Strategies for Molecular Diversification of 2-[Aminoalkyl-(1H-1,2,3-triazol-1- yl)]-1,4-naphthoquinones Using Click Chemistry

“…[4][5][6][7][8][9][10][11] This reaction has provided the opportunity to synthesize molecules having new properties or biological activities, 12,13 including anti-tuberculosis, 14 antiviral, 15 antitumoral, [16][17][18] antifungal, 19 antibiotic (e.g., tazobactam, see Figure 1a), 20 among others, as can be found in the literature. 21 Moreover, naphthoquinones moieties such as potent trypanocidal and leishmanicidal activities have been synthesized (Figure 1a).…”