New polyhydroxylated pyrrolidine, piperidine, and pyrrolizidine alkaloids from Scilla sibirica.
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.
Yamashita
Toru
T
Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
Yasuda
Kayo
K
Kizu
Haruhisa
H
Kameda
Yukihiko
Y
Watson
Alison A
AA
Nash
Robert J
RJ
Fleet
George W J
GW
Asano
Naoki
N
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
D004791:Enzyme Inhibitors; D008362:Mannosides; D010880:Piperidines; D011759:Pyrrolidines; D011763:Pyrrolizidine Alkaloids; D005696:Galactosidases; D005959:Glucosidases; D005644:alpha-L-Fucosidase