1245811-67-9Relevant academic research and scientific papers
Modular approach to triazole-linked 1,6-α-d-oligomannosides to the discovery of inhibitors of mycobacterium tuberculosis cell wall synthetase
Lo Conte, Mauro,Marra, Alberto,Chambery, Angela,Gurcha, Sudagar S.,Besra, Gurdyal S.,Dondoni, Alessandro
experimental part, p. 6326 - 6336 (2010/12/20)
Aiming at developing inhibitors of mannosyltransferases, the enzymes that participate in the biosynthesis of the cell envelope of Mycobacterium tuberculosis, the synthesis of a range of designed triazole-linked 1,6-oligomannosides up to a hexadecamer has been accomplished by a modular approach centered on the Cu(I)-catalyzed azide-alkyne cycloaddition as key process. The efficiency and fidelity of the cycloaddition are substantiated by high yields (76-96%) and exclusive formation of the expected 1,4-disubstituted triazole ring in all oligomer assembling reactions. Key features of oligomers thus prepared are the anomeric carbon-carbon bond of all mannoside residues and the 6-deoxymannoside capping residue. Suitable bioassays with dimer, tetramer, hexamer, octamer, decamer, and hexadecamer showed variable inhibitor activity against mycobacterial α-(1,6)-mannosyltransferases, the highest activity (IC50 = 0.14-0.22 mM) being registered with the hexamannoside and octamannoside.
