Recent Progress on Synthesis of Functionalized 1,5-Disubstituted Triazoles.

Immediately after the invention of 'Click Chemistry' in 2002, the regioselective 1,2,3- triazole scaffolds resulted from respective organic azides and terminal alkynes under Cu(I) catalysis have been well recognized as the functional heterocyclic core at the centre of modern organic chemistry, medicinal chemistry, and material sciences. This CuAAC reaction has several notable features including excellent regioselectivity, high-to-excellent yields, easy to execute, short reaction time, modular in nature, mild condition, readily available starting materials, etc. Moreover, the resulting regioselective triazoles can serve as amide bond isosteres, a privileged functional group in drug discovery and development. More than hundreds of reviews had been devoted to the 'Click Chemistry' in special reference to 1,4-disubstituted triazoles, while only little efforts were made for an opposite regioisomer i.e., 1,5-disubstituted triazole. Herein, we have presented various classical approaches for an expeditious synthesis of a wide range of biologically relevant 1,5- disubstituted 1,2,3-triazole analogues. The syntheses of such a class of diversly functionalized triazoles have emerged as a crucial investigation in the domain of chemistry and biology. This tutorial review covers the literature assessment on the development of various synthetic protocols for the functionalized 1,5-disubstituted triazoles reported during the last 12 years.

Design, synthesis, and docking study of saccharin N-triazolyl glycoconjugates.

To achieve better-repurposed motifs, saccharin has been merged with biocompatible sugar molecules via a 1,2,3-triazole linker, and ten novel 1,2,3-triazole-appended saccharin glycoconjugates were developed in good yield by utilizing modular CuAAC click as regioselective triazole forming tool. The docking study indicated that the resulting hybrid molecules have an overall substantial interaction with the CAXII macromolecule. Moreover, the galactose triazolyl saccharin analogue 3h has a binding energy of -8.5 kcal/mol with 5 H-bonds, and xylosyl 1,2,3-triazolyl saccharin analogue 3d has a binding energy of -8.2 kcal/mol with 6 H-bond interactions and have exhibited the highest binding interaction with the macromolecule system.

Organocatalyzed Regioselective Synthesis of 1,5-Disubstituted 1,2,3-Triazolyl Glycoconjugates.

A novel organocatalyzed [3+2] cycloaddition reaction of nitroolefins with glycosyl azides as well as organic azides has been developed for successful construction of 1,5-disubstituted triazolyl glycoconjugates. This metal-free and acid-free, regioselective synthetic protocol proceeds in the presence of only Schreiner thiourea organocatalysts, which enable the required activation of nitroolefins through double hydrogen bonding. The straightforward, operationally simple, and regioselectivity of this methodology, complementing to the classical RuAAC catalyzed synthesis of 1,5-disubstituted 1,2,3-triazoles. In the presence of catalytic amount of Schreiner thiourea organocatalyst, organic azides react with a broad array of nitroolefins producing a series of diverse 1,5-disubstituted 1,2,3- triazoles in good yields with excellent regioselectivity.

Pseudarthrosis of the surgical neck of humerus treated by buttressing with a medial cortico-cancellous graft.

BACKGROUND: Pseudarthrosis of surgical neck of humerus is uncommon condition. Different methods of improving the stability of fixation have been described, including impaling the shaft into the head, placing a tension suture through the rotator cuff, or using an intramedullary cortical graft. We report our results of cortico-cancellous strut graft medially to counter the varus force, in conjunction with a fixed-angle implant on the lateral side. MATERIALS AND METHODS: We used this technique in seven cases of pseudarthrosis of surgical neck of the humerus. There were four women and three men, ranging in age from 22 to 65 years. All were treated with a tricortical medial buttress bone graft and fixed-angle fixation device on the lateral side. A locking proximal humerus plate (Synthes) was used in six cases, and a bent reconstruction plate (Synthes) was applied in one case. The one in which reconstruction plate was applied was operated before the advent of locking plates. The limb was immobilized in 30° of abduction over a cushion for 6 weeks, followed by a sling for another 6 weeks. RESULTS: The followup varied from 18 to 96 months. All our cases healed within mean 5.1 months (range 4-6 months). There was one case of avascular necrosis. All cases had useful function of shoulder. CONCLUSION: The medial buttressing by strut graft with external fixation by laterally placed fixed angle plate is successful to achieve fracture union in pseudarthrosis of surgical neck of humerus.