Tetrazoles of manno- and rhamno-pyranoses: Contrasting inhibition of mannosidases by [4.3.0] but of rhamnosidase by [3.3.0] bicyclic tetrazoles
Davis BG., Brandstetter TW., Hackett L., Winchester BG., Nash RJ., Watson AA., Griffiths RC., Smith C., Fleet GWJ.
The synthesis of tetrazoles derived from D-manno and D- rhamnopyranose from L-gulonolactone and of L-rhamnopyranose from D-gulonolactone is described. These and other materials are assessed as inhibitors of glycosidases. The [4.3.0] tetrazoles of D-manno- and D-rhamnopyranose are inhibitors of human liver α-mannosidase. In contrast the D-furanose analogues show no inhibitory activity whilst the [3.3.0] L-rhamno furanotetrazole is a potent rhamnosidase inhibitor, a potential inhibitor of mycobacterial cell wall biosynthesis and as such may provide a strategy for the treatment of tuberculosis.