Glycosidase-inhibiting pyrrolidines and pyrrolizidines with a long side chain in Scilla peruviana

2,5-Dideoxy-2,5-imino-d-glycero-d-manno-heptitol (homoDMDP) is widely distributed in Hyacinthaceae plants and can also be regarded as the alpha-1-C-(1,2-dihydroxyethyl) derivative of 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1). In a search for glycosidase inhibitors in this family of plants, we isolated three new d-AB1 derivatives bearing the 2-hydroxypropyl (1), 1,2-dihydroxypropyl (2), and 1,5,7,12,13-pentahydroxytridecyl (3) side chains at the C-1alpha position, respectively, from the bulbs of Scilla peruviana. Alkaloid 3 was a powerful inhibitor of bacterial beta-glucosidase (IC(50) = 80 nM) and bovine liver beta-galactosidase (IC(50) = 90 nM). This plant coproduced four new pyrrolizidine alkaloids, alpha-5-C-(3-hydroxybutyl)-7-epi-australine (4), alpha-5-C-(3-hydroxybutyl)hyacinthacine A(1) (5), alpha-5-C-(1,3-dihydroxybutyl)hyacinthacine A(1) (6), and alpha-5-C-(1,3,4-trihydroxybutyl)hyacinthacine A(1) (7). Alkaloids 4 and 6 were potent inhibitors of yeast alpha-glucosidase, with IC(50) values of 6.6 and 6.3 microM, respectively, and alkaloid 6 was also a potent inhibitor of bacterial beta-glucosidase with an IC(50) value of 5.1 microM.