Département de chimie moléculaire

$\alpha$,$\alpha$-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 N-allylation and ring-closing metathesis afforded 8a-branched indolizidines, e.g., I, in high yield. The newly prepd. iminosugars demonstrated highly potent inhibition of $\alpha$-glucosidases. Most interestingly, compd. II exhibits very high selectivity toward this class of enzymes, with an unusual mode of binding. [on SciFinder(R)]