Hydroxymethyl-Branched Polyhydroxylated Indolizidines:Novel Selective α-Glucosidase Inhibitors.

α,α-Disubstituted piperidinesand conformationallyconstrained polyhydroxylated indolizidines bearing a hydroxymethylsubstituent in position 8a were synthesized from a readily available l-sorbose-derived ketonitrone. Diastereoselective vinylationunder two sets of complementary conditions allowed access to bothconfigurations of the newly formed quaternary stereocenter. Subsequent N-allylation and ring-closing metathesis afforded 8a-branchedindolizidines in high yield. The newly prepared iminosugars demonstratedhighly potent inhibition of α-glucosidases. Most interestingly,compound 9bexhibits very high selectivity toward thisclass of enzymes, with an unusual mode of binding. [ABSTRACT FROM AUTHOR]