Synthesis of selenium analogues of the naturally occurring glycosidase inhibitor salacinol and their evaluation as glycosidase inhibitors.
The syntheses of two selenium analogues (10 and 11) of the naturally occurring sulfonium ion, salacinol (3), are described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The synthetic strategy relies on the nucleophilic attack of a 2,3,5-tri-O-benzyl-1,4-anhydro-4-seleno-D-arabinitol at the least hindered carbon of benzyl- or benzylidene-protected D- or L-erythritol-1,3-cyclic sulfate. The use of 1,1,1,3,3,3-hexafluoro-2-propanol as a solvent in the coupling reaction proves to be beneficial. Enzyme inhibition assays indicate that 10 is a better inhibitor (K(i) = 0.72 mM) of glucoamylase than 3, which has a K(i) value of 1.7 mM. In contrast, 11 showed no significant inhibition of glucoamylase. Compounds 10 and 11 showed no significant inhibition of barley-alpha-amylase or porcine pancreatic-alpha-amylase.
Johnston
Blair D
BD
Department of Chemistry, Simon Fraser University, Burnaby, B.C., Canada V5A 1S6.
Ghavami
Ahmad
A
Jensen
Morten T
MT
Svensson
Birte
B
Pinto
B Mario
BM
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D001467:Hordeum / Q000201:enzymology; D016566:Organoselenium Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010179:Pancreas / Q000201:enzymology; D013402:Sugar Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013431:Sulfates; D013552:Swine; D000516:alpha-Amylases / Q000037:antagonists & inhibitors
D004791:Enzyme Inhibitors; D016566:Organoselenium Compounds; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol; D006026:Glycoside Hydrolases; D000516:alpha-Amylases; D005087:Glucan 1,4-alpha-Glucosidase