title: Synthesis of novel pyrrolidine 3,4-diol derivatives as inhibitors of alpha-L-fucosidases.
abstract: The stereoselective synthesis of new 3,4-dihydroxypyrrolidine derivatives starting from D-mannose, D-ribose and L-fucose is presented. Two synthetic strategies employing organometallic addition to hemiacetalic sugars followed by selective nucleophilic displacement or conjugate addition of ammonia to conjugate aldonic esters as key steps, are used. The new compounds were assayed for their inhibitory activity towards 13 commercially available glycosidases. Compounds that share the absolute configuration at C(2,3,4,5) of L-fucopyranosides and incorporate aromatic moieties are potent and selective inhibitors of alpha-L-fucosidases in the nM range.
authors.affiliation: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, P.O. Box 553, E-41071, Sevilla, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Moreno-Clavijo
authors.forename: Ana T
authors.initials: AT
authors.lastname: Carmona
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Vera-Ayoso
authors.forename: Antonio J
authors.initials: AJ
authors.lastname: Moreno-Vargas
authors.forename: Claudia
authors.initials: C
authors.lastname: Bello
authors.forename: Pierre
authors.initials: P
authors.lastname: Vogel
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Robina
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005643:Fucose / Q000737:chemistry; D008358:Mannose / Q000737:chemistry; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012266:Ribose / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors*
chemical_list: C540241:3,4-dihydroxypyrrolidine; D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D005643:Fucose; D012266:Ribose; D005644:alpha-L-Fucosidase; D008358:Mannose