Synthesis of polyhydroxylated cyclohexenyl sulfides and sulfoxides. Evaluation of their inhibitory activity on α- and β- d-glucosidases

Abstract

Racemic polyhydroxylated sulfides and sulfoxides have been prepared as potential transition-state analogs of the glucoside hydrolysis reaction, through a reaction sequence involving transformations of a ketone group into thioacetal, followed by partial oxidation to sulfoxide then regioselective thermal elimination of the sulfoxide to vinyl sulfide. These sulfides with two, three or four hydroxyl groups have been oxidized to the corresponding diastereoisomeric sulfoxides. All compounds, summarily tested as inhibitors of α- and β-glucosidases, were found to be very weak inhibitors and thus their biological properties were not studied in depth. Curiously, however, their inhibitory properties, which are in the 10 mM range, do not really depend upon the number of hydroxyl groups or upon the presence of polar sulfoxide. In order to get more insights, 2-phenyl sulfoxide-3,4,5-trihydroxycyclohex-1-ene ( 9a) was studied in more detail using Brewers yeast α-glucosidase and was shown to give a mixed-type inhibition with a high K i of 45 mM.