Probing the Intestinal alpha-Glucosidase Enzyme Specificities of Starch-Digesting Maltase-Glucoamylase and Sucrase-Isomaltase: Synthesis and Inhibitory Properties of 3 '- and 5 '-Maltose-Extended De-O-sulfonated Ponkoranol

作者：Eskandari Razieh; Jones Kyra; Reddy Kongara Ravinder; Jayakanthan Kumarasamy; Chaudet Marcia; Rose David R; Pinto B Mario^*

来源：Chemistry - A European Journal, 2011, 17(52): 14817-14825.

DOI：10.1002/chem.201102109

• enzyme catalysis
• inhibitors
• intestinal glucosidases
• maltose-extended-de-O-sulfonated ponkoranol
• sulfonium ions

The synthesis and glucosidase inhibitory activities of two C-3'- and C-5'-beta-maltose-extended analogues of the naturally occurring sulfonium-ion inhibitor, de-O-sulfonated ponkoranol, are described. The compounds are designed to test the specificity towards four intestinal glycoside hydrolase family 31 (GH31) enzyme activities, responsible for the hydrolysis of terminal starch products and sugars into glucose, in humans. The target sulfonium-ion compounds were synthesized by means of nucleophilic attack of benzyl protected 1,4-anhydro-4-thio-D-arabinitol at the C-6 position of 6-O-trifluoromethanesulfonyl trisaccharides as alkylating agents. The alkylating agents were synthesized from D-glucose by glycosylation at C-4 or C-2 with maltosyl trichloroacetimidate. Deprotection of the coupled products by using a two-step sequence, followed by reduction afforded the final compounds. Evaluation of the target compounds for inhibition of the four glucosidase activities indicated that selective inhibition of one enzyme over the others is possible.

• 出版日期2011-12