6,7-Diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase.
A tetrahydroxyindolizidine alkaloid, 6,7-diepicastanospermine, was isolated from the seeds of Castanospermum australe by extraction with methanol and purified to homogeneity using ion-exchange, preparative thin-layer, and radial chromatography. A very low yield of a pyrrolidine alkaloid, N-(hydroxyethyl)-2-(hydroxymethyl)-3-hydroxypyrrolidine, was also obtained by analogous methods. The purity of both alkaloids was established by gas chromatography of their trimethylsilyl (TMS) derivatives as better than 99%. The molecular weight of each alkaloid was established as 189 and 161, respectively, by mass spectrometry, and the structure of each was deduced from their 1H and 13C NMR spectra. The structure of the pyrrolidine alkaloid is suggestive of a possible biosynthetic route to the polyhydroxyindolizidine and polyhydroxypyrrolizidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal alpha-glucosidase, amyloglucosidase (Ki = 8.4 x 10(-5) M) and a relatively weak inhibitor of beta-glucosidase. It failed to inhibit alpha- or beta-galactosidase, alpha- or beta-mannosidase, or alpha-L-fucosidase. Comparison of its inhibitory activity toward amyloglucosidase with those of its isomers, castanospermine and 6-epicastanospermine, demonstrated that epimerization of a single hydroxyl group can produce significant alteration of such inhibitory properties.
Molyneux
R J
RJ
Western Regional Research Center, United States Department of Agriculture, Albany, California 94710.
Pan
Y T
YT
Tropea
J E
JE
Benson
M
M
Kaushal
G P
GP
Elbein
A D
AD
D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005087:Glucan 1,4-alpha-Glucosidase / Q000037:antagonists & inhibitors*; D006026:Glycoside Hydrolases / Q000378:metabolism; D007212:Indolizines / Q000302:isolation & purification* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D012639:Seeds / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014197:Trees; D054836:Indolizidines
D005087:Glucan 1,4-alpha-Glucosidase; D006026:Glycoside Hydrolases; D007212:Indolizines; C037806:castanospermine; D054836:Indolizidines