New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii.
Chromatographic separation of the pod extract of Angylocalyx pynaertii resulted in the isolation of 13 sugar-mimic alkaloids (1-13). The structures of the new alkaloids were elucidated by spectroscopic methods as the 6-O-beta-D-glucoside (10) and N-hydroxyethyl derivative (11) of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) (1), 1,6-dideoxynojirimycin (12), and 1,3,4-trideoxynojirimycin (13). 2,5-Imino-1,2,5-trideoxy-L-glucitol (7), 2,5-dideoxy-2,5-imino-D-fucitol (8), and beta-homofuconojirimycin (9), isolated from the pods as well as the bark, were very specific inhibitors of alpha-L-fucosidase with no significant inhibitory activity toward other glycosidases. In this work, 1,4-dideoxy-1,4-imino-D-ribitol (6) was found to be a better inhibitor of lysosomal beta-mannosidase than 2,5-imino-1,2,5-trideoxy-D-mannitol (2). N-Hydroxyethyl-1-deoxynojirimycin (miglitol), which is commercially available for the treatment of diabetes, retained its inhibitory potential toward rat intestinal maltase and sucrase, whereas 11 and the synthetic N-hydroxyethyl derivative of 2,5-dideoxy-2,5-imino-D-mannitol markedly lowered or abolished their inhibition toward all enzymes tested.
Yasuda
Kayo
K
Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan.
Kizu
Haruhisa
H
Yamashita
Toru
T
Kameda
Yukihiko
Y
Kato
Atsushi
A
Nash
Robert J
RJ
Fleet
George W J
GW
Molyneux
Russell J
RJ
Asano
Naoki
N
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000818:Animals; D002163:Cameroon; D002241:Carbohydrates / Q000737:chemistry*; D002417:Cattle; D003069:Coffee / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D007887:Fabaceae / Q000737:chemistry*; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007422:Intestines / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D012275:Oryza / Q000201:enzymology; D024301:Plant Bark; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015003:Yeasts / Q000201:enzymology
D000470:Alkaloids; D002241:Carbohydrates; D003069:Coffee; D004791:Enzyme Inhibitors; D006026:Glycoside Hydrolases; D005087:Glucan 1,4-alpha-Glucosidase