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

α,α-Disubstituted piperidines and conformationally constrained polyhydroxylated indolizidines bearing a hydroxymethyl substituent in position 8a were synthesized from a readily available l-sorbose-derived ketonitrone. Diastereoselective vinylation under two sets of complementary conditions allowed access to both configurations of the newly formed quaternary stereocenter. Subsequent <i>N</i>-allylation and ring-closing metathesis afforded 8a-branched indolizidines in high yield. The newly prepared iminosugars demonstrated highly potent inhibition of α-glucosidases. Most interestingly, compound <b>9b</b> exhibits very high selectivity toward this class of enzymes, with an unusual mode of binding