ABSTRACT
Bicyclic iminosugar derivatives with an ether bridge bearing different substituents on C-2 and the nitrogen atom have been synthesized from a C-glycoside bearing an isopropylidene acetal. The activities of these compounds were investigated against several glycosidase enzymes and showed moderate inhibition and activation.
Subject(s)
Bridged Bicyclo Compounds, Heterocyclic/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Ethers/chemistry , Imino Sugars/chemical synthesis , Imino Sugars/pharmacology , Animals , Cattle , Enzyme Activation/drug effects , Enzyme Inhibitors/chemistry , Glycoside Hydrolases/antagonists & inhibitors , Imino Sugars/chemistryABSTRACT
Iminoalditol analogs of ribopyranosides were prepared by reduction of a vinylogous urethane intermediate formed from methyl 2-C-(5-O-methanesulfonyl-beta-d-ribofuranosyl)acetate (1) by treatment with sodium azide in DMF at reflux. The N-alkylated analogs were synthesized either by N-alkylation of the corresponding parent iminoaldithol or, more efficiently, from the product of the reaction of 1 with various alkylamines. The latter process involves an S(N)2 substitution at C-5 by the amine followed by an intramolecular hetero-Michael reaction under basic conditions. The 'aglycon' of the iminoalditol was also modified through amidation and esterification.