Linda E. Fellows

Potent competitive inhibition of α-galactosidase and α-glucosidase activity by 1,4-dideoxy-1,4-iminopentitols: syntheses of 1,4-dideoxy-1,4-imino-d-lyxitol and of both enantiomers of 1,4-dideoxy-1,4-iminoarabinitol

Abstract The syntheses of 1,4-dideoxy-1,4-imino-D-lyxitol (3), 1,4-dideoxy-1,4-imino- d -arabinitol (4) and 1,4-dideoxy-1,4-imino- l -arabinitol (5) are reported; (3) is a potent competitive inhibitor of α-galactosidase (green coffee beans) and (4) a competitive inhibitor of α-glucosidase (Brewers yeast) suggesting that iminopentitols have considerable potential as glycosidase inhibitors. (4) was found to be identical to an alkaloid recently isolated from Angylocalyx boutiqueanus .

Glycosidase inhibition by plant alkaloids which are structural analogues of monosaccharides

Abstract ]The inhibitory activities of three plant alkaloids, deoxynojirimycin, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine and 1,5 dideoxy-1,5-imino- D -mannitol towards glycosidases from several sources have been compared. These are structural analogues of D -glucose, D -fructose and D -mannose respectively. The occurrence of 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine in Lonchocarpus sericeus seed is confirmed and has been shown to be responsible for the glucosidase inhibition wrongly attributed to 1,5-dideoxy-1,5-imino- D -mannitol in a previous report.

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.

Castanospermine in Alexa species

Abstract Castanospermine, a physiologically active polyhydroxylated indolizidine alkaloid first isolated from seeds of Castanospermum australe, has been isolated from the dried pod of Alexa leiopetala and tentatively identified in seven other species of the same genus.

Behavioral and electrophysiological study of antifeedant mechanisms associated with polyhydroxy alkaloids

Eleven polyhydroxy alkaloids of plant origin were tested for anti-feedant effects against larvae of the lepidopteransSpodoptera littoralis, Spodoptera frugiperda, Heliothis virescens, andHelicoverpa armigera. Data from behavioral and electrophysiological investigations were correlated to reveal information on the mode of action of the antifeedants. The pyrrolidine DMDP was an effective antifeedant for all four species, whereas the piperidines fagomine and XZ-1 and the pyrrolizidine alexine were all ineffective as antifeedants. The activity of the pyrrolidines CYB-3 and DAB-1, the piperidines DNJ, DMJ, and BR1, and the bicyclic octahydroindolizine castanospermine varied among species. The investigation focuses on the structural similarities between some of the alkaloids and some common phagostimulatory sugars and illustrates a neural interaction involving the neurons that are differentially responsive to alkaloids and sugars. InS. littoralis, the neurons responding specifically to the alkaloids DMDP, DAB-1, and castanospermine and to the sugars fructose, sucrose, and glucose are more active when the compounds are applied singly than when an alkaloid and a sugar are applied together. The implications for the occurrence and functioning of different sugar receptor sites are discussed.

Synthesis of deoxymannojirimycin fagomine deoxynojirimycin 2-acetamido-1,5-imino-1,2,5-trideoxy-D-mannitol 2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol 2S,3R,4R,5R-trihydroxypipecolic acid and 2S,3R,4R,5S-trihydroxypipecolic acid from methyl 3-O-benzyl-2,6-dideoxy-2,6-imino-α-D-mannofuranoside

Abstract The value of methyl 3-O-benzyl-2,6-dideoxy-2,6-imino-α-D-mannofuranoside as a divergent intermediate for the preparation of polyhydroxylated piperidines is illustrated by the synthesis of deoxymannojirimycin (1,5-dideoxy-1,5-imino-D-mannitol), fagomine (1,5-imino-1,2,5-trideoxy-D-( arabino -hexitol), deoxynojirimycin (1,5-dideoxy-1,5-imino-D-glucitol), 2-acetamido-1,5-imino-1,2,5-trideoxy-D-mannitol, 2-acetamido-1,5-imino-1,2,5-trideoxy-D-glucitol, 2S,3R,4R, 5R-trihydroxypipecolic acid and 2S,3R,4R,5S-trihydroxypipecolic acid.

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.

Neo-clerodane insect antifeedants from Scutellaria galericulata

Abstract Four neo-clerodane diterpenoids have been isolated from aerial material of Scutellaria galericulata . Three compounds, jodrellin T, 14,15-dihydrojodrellin T and galericulin, are novel structures. The fourth, jodrellin B has been previously isolated from Scutellaria woronowii . Jodrellin B is amongst the most potent neo-clerodane antifeedants so far described, 14,15-dihydrojodrellin T is also active. Chemical structures were rigorously determined by spectroscopic methods.