Total syntheses of casuarine and its 6-O-alpha-glucoside: complementary inhibition towards glycoside hydrolases of the GH31 and GH37 families.
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.
Cardona
Francesca
F
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.
Parmeggiani
Camilla
C
Faggi
Enrico
E
Bonaccini
Claudia
C
Gratteri
Paola
P
Sim
Lyann
L
Gloster
Tracey M
TM
Roberts
Shirley
S
Davies
Gideon J
GJ
Rose
David R
DR
Goti
Andrea
A
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
D000470:Alkaloids; D004791:Enzyme Inhibitors; D005960:Glucosides; D011758:Pyrroles; C409108:casuarine; D006026:Glycoside Hydrolases; D014198:Trehalase; D005087:Glucan 1,4-alpha-Glucosidase