Homonojirimycin analogues and their glucosides from Lobelia sessilifolia and Adenophora spp. (Campanulaceae)

Abstract

2,6-Dideoxy-7- O-(β- d-glucopyranosyl) 2,6-imino- d- glycero- l- gulo-heptitol (7- O-β- d-glucopyranosyl-α-homonojirimycin, 1) was isolated from the 50% methanol extract of the whole plant of Lobelia sessilifolia (Campanulaceae), which was found to potently inhibit rice α-glucosidase. Adenophorae radix, roots of Adenophora spp. (Campanulaceae), yielded new homonojirimycin derivatives, adenophorine ( 2), 1-deoxyadenophorine ( 3), 5-deoxyadenophorine ( 4), 1- C-(5-amino-5-deoxy-β- d-galactopyranosyl)butane (β-1- C-butyl-deoxygalactonojirimycin, 5), and the 1- O-β- d-glucosides of 2 ( 6) and 4 ( 7), in addition to the recently discovered α-1- C-ethylfagomine ( 8) and the known 1-deoxymannojirimycin ( 9) and 2 R,5 R-bis(hydroxymethyl)-3 R,4 R-dihydroxypyrrolidine (DMDP, 10). Compound 4 is a potent inhibitor of coffee bean α-galactosidase (IC 50=6.4 μM) and a reasonably good inhibitor of bovine liver β-galactosidase (IC 50=34 μM). Compound 5 is a very specific and potent inhibitor of coffee bean α-galactosidase (IC 50=0.71 μM). The glucosides 1 and 7 were potent inhibitors of various α-glucosidases, with IC 50 values ranging from 1 to 0.1 μM. Furthermore, 1 potently inhibited porcine kidney trehalase (IC 50=0.013 μM) but failed to inhibit α-galactosidase, whereas 7 was a potent inhibitor of α-galactosidase (IC 50=1.7 μM) without trehalase inhibitory activity.