title: Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families.
abstract: Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.
authors.affiliation: Department of Organic Chemistry U. Schiff, Laboratory of Design, Synthesis and Study of Biologically Active Heterocycles, University of Florence, Via della Lastruccia, 13, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Cardona
authors.forename: Camilla
authors.initials: C
authors.lastname: Parmeggiani
authors.forename: Enrico
authors.initials: E
authors.lastname: Faggi
authors.forename: Claudia
authors.initials: C
authors.lastname: Bonaccini
authors.forename: Paola
authors.initials: P
authors.lastname: Gratteri
authors.forename: Lyann
authors.initials: L
authors.lastname: Sim
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Gloster
authors.forename: Shirley
authors.initials: S
authors.lastname: Roberts
authors.forename: Gideon J
authors.initials: GJ
authors.lastname: Davies
authors.forename: David R
authors.initials: DR
authors.lastname: Rose
authors.forename: Andrea
authors.initials: A
authors.lastname: Goti
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000378:metabolism*; D020134:Catalytic Domain; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism*; D005087:Glucan 1,4-alpha-Glucosidase / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis* / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism*; D006860:Hydrogen Bonding; D007700:Kinetics; D011758:Pyrroles / Q000138:chemical synthesis* / Q000378:metabolism*; D014198:Trehalase / Q000378:metabolism
chemical_list: D000470:Alkaloids; D004791:Enzyme Inhibitors; D005960:Glucosides; D011758:Pyrroles; C409108:casuarine; D006026:Glycoside Hydrolases; D014198:Trehalase; D005087:Glucan 1,4-alpha-Glucosidase