title: Synthesis and glycosidase inhibition of australine and its fluorinated derivatives.
abstract: Australine (1), 7-epi-australine (2), and their C-7-fluorinated derivatives 4 and 5 have been synthesized efficiently from D-arabinose-derived cyclic nitrone 11. Fluorination at the C-7 position enhanced the inhibition against A. niger α-glucosidase, and this constitutes the first example of fluorination substitution for a hydroxyl increasing the inhibition of any glycosidases. The enantiomers synthesized from nitrone ent-11 showed no inhibition of the corresponding enzymes.
authors.affiliation: Beijing National Laboratory for Molecular Science (BNLMS), CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Yi-Xian
authors.initials: YX
authors.lastname: Li
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kasumi
authors.initials: K
authors.lastname: Sato
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yue-Mei
authors.initials: YM
authors.lastname: Jia
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
authors.forename: Chu-Yi
authors.initials: CY
authors.lastname: Yu
mesh_terms: D001089:Arabinose / Q000031:analogs & derivatives / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000187:drug effects; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009589:Nitrogen Oxides / Q000737:chemistry; D011763:Pyrrolizidine Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000520:alpha-Glucosidases
chemical_list: D004791:Enzyme Inhibitors; D006845:Hydrocarbons, Fluorinated; D009589:Nitrogen Oxides; D011763:Pyrrolizidine Alkaloids; C015388:nitrones; C059794:australine; D001089:Arabinose; D006026:Glycoside Hydrolases; D000520:alpha-Glucosidases