Synthesis of D-lyxitol and D-ribitol analogues of the naturally occurring glycosidase inhibitor salacinol.
The synthesis of analogues of the naturally occurring glycosidase inhibitor, salacinol, in which the D-arabinitol ring has been replaced by D-lyxitol or D-ribitol, is described. Salacinol is one of the active principles in the aqueous extracts of Salacia reticulata, which are traditionally used in India and Sri Lanka for the treatment of Type II diabetes. The synthetic strategy relies on the nucleophilic attack of 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-lyxitol or 1,4-anhydro-2,3,5-tri-O-p-methoxybenzyl-4-thio-D-ribitol at the least hindered carbon of the benzylidene-protected L-cyclic sulfate derived from L-erythritol. Screening of these compounds against recombinant human maltase glucoamylase (MGA), a critical intestinal glucosidase involved in the processing of oligosaccharides of glucose into glucose itself, shows that they are not effective inhibitors of MGA and demonstrates the importance of the d-arabinitol configuration in the heterocyclic ring for effective inhibition.
Kumar
Nag S
NS
Department of Chemistry, Simon Fraser University, Burnaby, British Columbia, Canada V5A 1S6.
Pinto
B Mario
BM
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007202:Indicators and Reagents; D008958:Models, Molecular; D009844:Oligosaccharides / Q000494:pharmacology*; D012255:Ribitol / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013402:Sugar Alcohols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013431:Sulfates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D009844:Oligosaccharides; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol; D012255:Ribitol; D006026:Glycoside Hydrolases