Carbasugar-thioether pseudodisaccharides related to N-glycan biosynthesis.
Analogues of the alpha-Glcp-(1-->3)-alpha-Glcp and alpha-Glcp-(1-->3)-alpha-Manp disaccharides (representing the two alpha-gluco linkages cleaved by alpha-Glucosidase II in N-glycan biosynthesis) in which the non-reducing-end sugar is replaced by a carbasugar and the inter-glycosidic oxygen by a sulfur were synthesised. The key coupling step was an S(N)2 displacement of an equatorial triflate at C-1 of the carbasugar by C-3 gluco or manno thiolates with inversion of configuration to give thioether pseudodisaccharides with axial substitution at C-1 of the carbasugar. The deprotected pseudodisaccharides failed to inhibit the action of alpha-Glucosidase II as measured both by an in vitro assay and by free oligosaccharide (FOS) analysis from cell studies.
Cumpstey
Ian
I
Department of Organic Chemistry, Stockholm University, Arrhenius Laboratory, Stockholm, Sweden. cumpstey@organ.su.se
Alonzi
Dominic S
DS
Butters
Terry D
TD
D054329:Carbasugars / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013440:Sulfides / Q000737:chemistry*; D000520:alpha-Glucosidases / Q000378:metabolism
D054329:Carbasugars; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D013440:Sulfides; D000520:alpha-Glucosidases