Polyhydroxylated pyrrolidine and pyrrolizidine alkaloids from Hyacinthoides non-scripta and Scilla campanulata

Aqueous ethanol extracts from the immature fruits and stalks of bluebell (Hyacinthoides non-scripta) were subjected to various ion-exchange column chromatographic steps to give 1,4-dideoxy-1,4-imino-d-arabinitol (1), 2(R),5(R)-bis(hydroxymethyl)-3(R),4(R)-dihydroxypyrrolidine (DMDP) (2), 6-deoxy-6-C-(2,5-dihydroxyhexyl)-DMDP (3), 2,5-dideoxy-2,5-imino-dl-glycero-d-manno-heptitol (homoDMDP) (4), homoDMDP-7-O-apioside (5), homoDMDP-7-O-β-d-xylopyranoside (6), (1S*,2R*,3R*,5R*,7aR*)-1,2-dihydroxy-3,5-dihydroxymethylpyrrolizidine (7), and (1S*,2R*,3R*,5R*,6R*,7R*,7aR*)-3-hydroxymethyl-5-methyl-1,2,6,7-tetrahydroxypyrrolizidine (8). Bulbs of Scilla campanulata (Hyacinthaceae) yielded (1S*,2R*,3R*,5S*,7aR*)-1,2-dihydroxy-3,5-dihydroxymethylpyrrolizidine (9) in addition to compounds 1–7. Compounds 3, 6, 7, 8, and 9 are new natural products. Compound 4 is a potent competitive inhibitor with Ki values of 1.5 μM for Caldocellum saccharolyticum β-glucosidase and 2.2 μM for bovine liver β-galactosidase. The 7-O-β-d-xyloside 6 was a stronger competitive inhibitor than 4 of C. saccharolyticum β-glucosidase and rat intestinal lactase, with Ki values of 0.06 and 0.07 μM, respectively, but a weaker inhibitor of bovine liver β-galactosidase. Furthermore, compound 4 is also a competitive inhibitor (Ki=1.8 μM) of porcine kidney trehalase, but 6 was inactive against this enzyme.