title: New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica.
abstract: Chromatographic separation of an extract of the bulbs of Scilla sibirica resulted in the isolation of five pyrrolidines, two pyrrolidine glycosides, six piperidines, one piperidine glycoside, and eight pyrrolizidines. 2,5-Dideoxy-2,5-imino-glycero-d-manno-heptitol (homoDMDP, 1) is a common alkaloid in all plants of the Hyacinthaceae examined to date and was also found in S. sibirica. The structures of the new alkaloids were elucidated by spectroscopic methods as 7-deoxy-homoDMDP (4), 2,5-dideoxy-2,5-imino-glycero-d-galacto-heptitol (5), the 4-O-beta-d-mannoside (6) and the 4-O-beta-d-mannobioside (7) of 6-deoxy-homoDMDP (2), 7-deoxyhomonojirimycin (12), 7-deoxyhomomannojirimycin (13), and polyhydroxypyrrolizidines, hyacinthacines A(4) (15), A(5) (16), A(6) (17), A(7) (18), B(4) (20), B(5) (21), and B(6) (22). HomoDMDP (1) is a potent inhibitor of beta-glucosidase and beta-galactosidase, while 6-deoxy-homoDMDP (2) showed significantly less inhibition. However, 7-deoxygenation of 1, leading to 4, showed no effect on the inhibitory activity toward both enzymes. Although 2 is not an inhibitor of alpha-l-fucosidase, the monomannoside of 2 shows inhibitory activity toward alpha-l-fucosidase. Elongation of the beta-mannopyranosyl chain of 6 to give 7 enhanced the inhibitory activity.
authors.affiliation: Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Kayo
authors.initials: K
authors.lastname: Yasuda
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Kizu
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kameda
authors.forename: Alison A
authors.initials: AA
authors.lastname: Watson
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nash
authors.forename: George W J
authors.initials: GW
authors.lastname: Fleet
authors.forename: Naoki
authors.initials: N
authors.lastname: Asano
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005696:Galactosidases / Q000037:antagonists & inhibitors; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D008362:Mannosides / Q000037:antagonists & inhibitors; D008968:Molecular Conformation; D018716:Molecular Mimicry; D015394:Molecular Structure; D009426:Netherlands; D019906:Nuclear Magnetic Resonance, Biomolecular; D010407:Penicillium / Q000201:enzymology; D010880:Piperidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011763:Pyrrolizidine Alkaloids / Q000737:chemistry / Q000302:isolation & purification*; D051381:Rats; D031445:Scilla / Q000737:chemistry*; D013237:Stereoisomerism; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D008362:Mannosides; D010880:Piperidines; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D005696:Galactosidases; D005959:Glucosidases; D005644:alpha-L-Fucosidase