Modular approach to triazole-linked 1,6-α-D-oligomannosides to the discovery of inhibitors of Mycobacterium tuberculosis cell wall synthetase.
J Org Chem
; 75(19): 6326-36, 2010 Oct 01.
Article
in En
| MEDLINE
| ID: mdl-20822121
ABSTRACT
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 (IC(50) = 0.14-0.22 mM) being registered with the hexamannoside and octamannoside.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligosaccharides
/
Triazoles
/
Cell Wall
/
Enzyme Inhibitors
/
Mannosyltransferases
/
Mycobacterium tuberculosis
Language:
En
Journal:
J Org Chem
Year:
2010
Document type:
Article
Affiliation country:
Italy