Anthony M. Scofield

Inhibition of mammalian digestive disaccharidases by polyhydroxy alkaloids.

Several polyhydroxy alkaloids, including the eight presently known to occur in plants, have been compared as inhibitors of mouse gut digestive disaccharidases. The indolizidine castanospermine inhibited all activities tested, but others showed a selectivity which could be of value in studies of carbohydrate digestion and errors of metabolism.

Isolation from and x-ray crystal structure of alexine, (1r,2r,3r,7s,8s)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine [(2r,3r,4r,5s,6s)-2-hydroxymethyl-1-azabicyclo[3.3.0]octan-3,4,6-triol], a unique pyrrolizidine alkaloid

Abstract The isolation from Alexa leiopetala and identification by X-ray crystal structure analysis of (1R,2R,3R,7S,8S)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine [(2R,3R,4R,5S,6S)-2-hydroxymethyl-1-azabicyclo[3.3.0]octan-3,4,6-triol], a unique pyrrolizidine alkaloid, is described. A preliminary study of the inhibition of glycosidases by alexine is reported.

α-Homonojirimycin [2,6-dideoxy-2,6-imino-d-glycero-l-gulo-heptitol] from omphalea diandra L.: isolation and glucosidase inhibtion

Abstract The isolation of α-homonojirimycin [2,6-dideoxy-2,6-imino-D-glycero-L-gulo-heptitol] from Omphalea diandra is described; α-homonojirimycin is an inhibitor of several α-glucosidases.

Two alexines [3-hydroxymethyl-1,2,7-trihydroxypyrrolizidines] from Castanospermum australe

Abstract Two new alexines have been isolated from Castanospermum australe . The structure of 1,7a-diepialexine was firmly established by X-ray crystallographic analysis of the corresponding 1,7-isopropylidene derivative. The structure of the second new alexine was tentatively assigned as 7,7a-diepialexine or its enantiomer. The abilities of naturally occurring alexines to inhibit mouse gut disaccharidase and fungal glucan 1,4-α-glucosidase are compared.

Isolation from castanospermum australe and x ray crystal structure of 3 8 diepialexine 1r 2r 3s 7s 8r 3 hydroxymethyl 1 2 7 trihydroxypyrrolizidine 2s 3r 4r 5s 6r 2 hydroxymethyl 1 azabicyclo 3.3.0 octan 3 4 6 triol

Abstract The isolation from Castanospermum australe and identification by X-ray crystal structure analysis of (1R,2R,3S,7S,8R)-3-hydroxymethyl-1,2,7-trihydroxypyrrolizidine [(2S,3R,4R,5S,6R)-2-hydroxymethyl-1-azabicyclo[3.3.0]octan-3,4,6-triol], the second example of a pyrrolizidine alkaloid with a carbon substituent at C-1, is described. A study of the inhibition of glycosidases by 3,8-diepialexine is reported.

α-Homonojirimycin and 2,5-dihydroxymethyl-3,4-dihydroxy-pyrrolidine: Alkaloidal glycosidase inhibitors in the moth Urania fulgens

Abstract Adults, pupae and eggs of the neotropical moth, Urania fulgens, contain a-homonojirimycin and 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, two of the alkaloidal glycosidase inhibitors that occur in the larval foodplant, Omphalea diandra . This is the first report of the occurrence of such compounds in animals.

Inhibition of thioglucosidase-catalysed glucosinolate hydrolysis by castanospermine and related alkaloids

Abstract The ability of some naturally occurring polyhydroxyalkaloids to inhibit the hydrolysis of the glucosinolates, sinigrin (allylglucosinolate) and progoitrin [(2R)-2-hydroxybut-3-enylglucosinolate], by thioglucosidases from mustard and the cabbage aphid, Brevicoryne brassicae, was assessed. Several compounds, in particular castanospermine, DMDP and alexine were effective. The inhibitory activity varied according to substrate, buffer composition and pH, and enzyme source.

CASTANOSPERMINE AND OTHER POLYHYDROXY ALKALOIDS AS INHIBITORS OF INSECT GLYCOSIDASES

Abstract The inhibition of glycosidase activity by a range of polyhydroxy alkaloids was studied in a number of insect species from the orders Orthoptera, Phasmida, Dictyoptera, Diptera and Coleoptera. Glycosidase activity was inhibited by a number of the alkaloids and the pattern of inhibition of hydrolysis of β-glucosides and most α-glucosides (except trehalose) was different from that in mammals. 2R,5R-dihydroxymethyl-3R,4R-dihydroxypyrrolidine inhibited both α-glucosidase, including trehalase, and β-glucosidase activity strongly in insects while castanospermine was a significant inhibitor only of β-glucosidase activity, trehalase and in the Tenebrionidae, isomaltase and additionally, maltase in Zophobas morio. The identification of an isomaltase in the Tenebrionidae illustrates the value of the alkaloids as taxonomic tools.

Isolation of 7a-epialexaflorine from leaves of alexa grandiflora a unique pyrrolizidine amino acid with a carboxylic acid substituent at C-3

Abstract The isolation and identification by X-ray crystal structure analysis of 7a-epialexaflorine (1R,2R,3S,7S,7aR)-3-carboxy-1,2,7-trihydroxypyrrolizidine, the first example of a naturally occurring pyrrolizidine-3-carboxylic acid, from Alexa grandiflora is described.

Castanospermine, Swainsonine and Related Polyhydroxy Alkaloids: Structure, Distribution and Biological Activity

Alkaloids which are inhibitors of glycosidases are now believed to be widespread in plants and microorganisms. Those isolated to date carry several hydroxyl substituents on a ring in a configuration that suggests a structural resemblance to monosaccharides. Despite their relatively recent detection (most have been discovered during the last ten years), they are now providing molecular biologists with tools with which to probe many hitherto intractable problems of molecular biology, including cancer metastasis, viral infectivity and the immune response. One, castanospermine, is under evaluation as a drug for the clinical management of HIV infection (AIDS). This paper outlines their structural range, natural distribution and biological activity.