Synthesis of analogues of salacinol containing a carboxylate inner salt and their inhibitory activities against human maltase glucoamylase.
The syntheses of analogues of the naturally occurring glycosidase inhibitor, salacinol, containing a carboxylate inner salt are described. Salacinol is a sulfonium ion with an internal sulfate counterion. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri-O-benzyl-4-thio-D- or L-arabinitol at the least hindered carbon of 4,5-anhydro-2,3-O-isopropylidene-D-ribonic acid benzyl ester to yield coupled adducts. Deprotection of the coupled products gives the target compounds. The compound derived from D-arabinitol inhibits recombinant human maltase glucoamylase, one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine, with a Ki value of 10+/-1 microM.
Chen
Wang
W
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Sim
Lyann
L
Rose
David R
DR
Pinto
B Mario
BM
D004791:Enzyme Inhibitors / Q000138:chemical synthesis; D065089:Glycoside Hydrolase Inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D013431:Sulfates / Q000138:chemical synthesis* / Q000737:chemistry; D013452:Sulfonium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000520:alpha-Glucosidases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D013402:Sugar Alcohols; D013431:Sulfates; D013452:Sulfonium Compounds; C427963:salacinol; D006026:Glycoside Hydrolases; D000520:alpha-Glucosidases