A divergent entry to 1,2,3,9-tetrahydroxyquinolizidines

Polyhydroxylated quinolizidines should be expected to show high inhibitory activity for glycosidases, similar to other polyhydroxylated nitrogen-containing heterocycles, however, very few investigations into the synthesis and biological evaluations of polyhydroxylated quinolizidines have been reported. We achieved the enantiodivergent synthesis of polyhydroxylated quinolizidines (1S, 2S, 3S, 9S, 9aR)-1,2,3,9-tetrahydroxyquinolizidine 8 and its enantiomer starting from the key intermediate (5S, 6S)-1-allyl-6-((R)-1-hydroxyallyl)-5-(methoxymethoxy)piperidin-2-one 7 via (1S, 9R, 9aS)-9-hydroxy-1-(methoxymethoxy)-2, 3, 9, 9a-tetrahydro-1H-quinolizin-4(6H)-one 13 having the pseudo-symmetry. In addition, two diastereomeric quinolizidines (1R, 2S, 3S, 9S, 9aR)-1,2,3,9-tetrahydroxyquinolizidine 9 and (1R, 2R, 3R, 9S, 9aR)-1,2,3,9-tetrahydroxyquinolizidine 10 were also synthesized from common intermediate 7.