Synthesis of 2-amido, 2-amino, and 2-azido derivatives of the nitrogen analogue of the naturally occurring glycosidase inhibitor salacinol and their inhibitory activities against O-GlcNAcase and NagZ enzymes

Inhibitors for Bacterial Cell-Wall Recycling

“…31 Small molecule inhibition of NagZ attenuates βlactamase expression with concomitant improvement in in vitro β-lactam efficacy, in both E. coli and P. aeruginosa. 32−34 Given the successful application of structure-based design toward potent and selective GlcNAc pyranosylidene aminocarbamate inhibitors of NagZ 35,36 and the proven synthetic strategies toward improved iminosaccharide inhibitor efficacy, [6][7][8][9][10][11][12][13][14][15][16]20,37,38 our observation of potent NagZ inhibition by a piperidinebased GlcNAc iminosaccharide augurs well for future application of the iminosaccharide for small molecule interrogation of these pathways. 36,39 Moreover, as it has now been proven that peptidoglycan recycling occurs in at least one Gram-positive bacterium (Bacillus subtilis) 40 and engages a mechanistically distinct NagZ ortholog, 41 this inhibitor class may have broad-spectrum implications toward efforts to preserve clinical relevance for the β-lactam antibiotics.…”

Iridium-catalysed condensation of alcohols and amines as a method for aminosugar synthesis

“…[8][9][10][11][12][13][14] To date, the substrate scope has been limited to rather simple molecules. The reactivity of carbohydrate alcohols in the catalytic amination reaction does not appear to be known, while the catalytic alkylation of carbohydrate amines with simple alcohols (as solvents) over heterogeneous catalysts has been reported, 15 but not studied in detail. Focussing on the [Cp*IrCl 2 ] 2 complexz as introduced by Fujita et al, 8 we have examined the scope of the reaction with respect to functionalisation of carbohydrate amines with alcohols; and also the functionalisation of carbohydrate alcohols with amines, including regioselectivity aspects.…”

Detection and Analysis of Proteins Modified by O‐Linked N‐Acetylglucosamine

“…Several inhibitors exist (Choubdar et al 2008; Dennis et al 2006; Dorfmueller et al 2006; Dorfmueller and van Aalten; Kim et al 2007; Kim et al; Kim et al 2006; Laczy et al; Lee et al 2006; Macauley et al 2005; Scaffidi et al 2007; Shanmugasundaram et al 2006; Stubbs et al 2006; Whitworth et al 2007; Yuzwa et al 2008), although only PUGNAc (Toronto Research Chemicals; (Haltiwanger et al 1998) and Thiamet-G (Cayman Chemicals; (Yuzwa et al 2008)) are commercially available. Unlike Thiamet-G, PUGNAc also inhibits lysosomal hexosaminidases.…”

“…In cultured mammalian cells, as well as tissue slices and tissues in vivo, the number of O-GlcNAc moieties per protein molecule can be increased by treating cells/tissues/animals with inhibitors of O-GlcNAcase. Several inhibitors exist (Macauley et al, 2005;Dennis et al, 2006;Dorfmueller et al, 2006;Kim et al, 2006Kim et al, , 2007Lee et al, 2006;Shanmugasundaram et al, 2006;Stubbs et al, 2006;Scaffidi et al, 2007;Whitworth et al, 2007;Choubdar et al, 2008;Yuzwa et al, 2008;Laczy et al, 2010), although only PUGNAc (Toronto Research Chemicals; Haltiwanger et al, 1998) and Thiamet-G (Cayman Chemicals; Yuzwa et al, 2008) are commercially available. Unlike Thiamet-G, PUGNAc also inhibits lysosomal hexosaminidases.…”