title: Synthesis and conformational analysis of bicyclic sulfonium salts. Structures related to the glycosidase inhibitor australine.
abstract: The syntheses of eight sulfonium compounds with structures related to the naturally occurring pyrrolizidine alkaloid, australine, in which the bridgehead nitrogen atom is replaced by a sulfonium ion, are described. The synthetic strategy relies on the intramolecular attack of a cyclic thioether across a terminal double bond in the presence of a suitable electrophile. We postulate that these compounds, having a permanent positive charge on the sulfur atom, will mimic the highly unstable oxacarbenium ion transition state in a glycosidase-catalyzed hydrolysis reaction. The conformational preferences of these compounds, based on analysis of 1H-1H vicinal coupling constants and 1D-NOESY data, are attributed to both steric and electrostatic interactions. These compounds will be used in the study of structure-activity relationships with glycosidase enzymes.
authors.affiliation: Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
authors.forename: Nag S
authors.initials: NS
authors.lastname: Kumar
authors.forename: B Mario
authors.initials: BM
authors.lastname: Pinto
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011763:Pyrrolizidine Alkaloids; D013329:Structure-Activity Relationship; D013452:Sulfonium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006574:Heterocyclic Compounds, 2-Ring; D011763:Pyrrolizidine Alkaloids; D013452:Sulfonium Compounds; C059794:australine; D006026:Glycoside Hydrolases