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Josephine M. Peach - One of the best experts on this subject based on the ideXlab platform.
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X-ray crystal structure of the hydrochloride of 6-epicastanospermine [(1S,6R,7R,8R,8aR)-1,6,7,8-tetrahydroxy-octahydroindolizine]
Phytochemistry, 1990Co-Authors: Robert J Nash, George W J Fleet, Linda E. Fellows, Aarti Girdhar, Josephine M. Peach, David J. Watkin, Mervyn P. HegartyAbstract:Abstract The X-ray crystal structure of the hydrochloride of 6-epicastanospermine [1 S ,6 R ,7 R ,8 R ,8 aR )-1,6,7,8-tetrahydroxyoctahydroindolizine], isolated from Castanospermum australe , is reported.
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two alexines 3 hydroxymethyl 1 2 7 trihydroxypyrrolizidines from Castanospermum australe
Phytochemistry, 1990Co-Authors: Robert J Nash, George W J Fleet, Linda E. Fellows, Aarti Girdhar, Josephine M. Peach, Janet V. Dring, Nigel RamsdenAbstract: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.
Robert J Nash - One of the best experts on this subject based on the ideXlab platform.
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isolation and sar studies of bicyclic iminosugars from Castanospermum australe as glycosidase inhibitors
Phytochemistry, 2015Co-Authors: Atsushi Kato, Robert J Nash, Yuki Hirokami, Kyoko Kinami, Yutaro Tsuji, Shota Miyawaki, Isao Adachi, Jackie Hollinshead, J L Kiappes, Nicole ZitzmannAbstract:We report the isolation and structural determination of fourteen iminosugars, containing five pyrrolizidines and five indolizidines, from Castanospermum australe. The structure of a new alkaloid was elucidated by spectroscopic methods as 6,8-diepi-castanospermine (13). Our side-by-side comparison between bicyclic and corresponding monocyclic iminosugars revealed that inhibition potency and spectrum against each enzyme are clearly changed by their core structures. Castanospermine (10) and 1-deoxynojirimycin (DNJ) have a common d-gluco configuration, and they showed the expected similar inhibition potency and spectrum. In sharp contrast, 6-epi-castanospermine (12) and 1-deoxymannojirimycin (manno-DNJ) both have the d-manno configuration but the α-mannosidase inhibition of 6-epi-castanospermine (12) was much better than that of manno-DNJ. 6,8-Diepi-castanospermine (13) could be regarded as a bicyclic derivative of talo-DNJ, but it showed a complete loss of α-galactosidase A inhibition. This behavior against α-galactosidase A is similar to that observed for 1-epi-australine (6) and altro-DMDP.
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isolation of the pyrrolizidine alkaloid 1 epialexine from Castanospermum australe
Phytochemistry Letters, 2010Co-Authors: Laurence Edmund Jones, George W J Fleet, David J. Watkin, Jacqueline Hollinshead, Amber L Thompson, Sarah F Jenkinson, Atsushi Kato, Robert J NashAbstract:Abstract The Australian leguminous tree Castanospermum australe contains the anti-viral glucose analogue indolizidine alkaloid castanospermine. As the result of a search for new bioactive carbohydrate-like compounds we now report the isolation of the novel polyhydroxylated pyrrolizidine alkaloid, 1-epialexine, from the leaves and stems of C. australe. 1-Epialexine is a weak inhibitor of β-mannosidase from Cellullomonas fimi.
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Australine and related alkaloids: easy structural confirmation by 13C NMR spectral data and biological activities
Tetrahedron-asymmetry, 2003Co-Authors: Atsushi Kato, Russell J. Molyneux, Robert J Nash, George W J Fleet, Mark R. Wormald, Isao Adachi, Erika Kano, Alison A. Watson, Haruhisa Kizu, Kyoko IkedaAbstract:Abstract The first polyhydroxylated pyrrolizidine alkaloid with a hydroxymethyl group at C-3 was isolated from pods of Alexa leiopetala (Leguminosae) and designated alexine 1. The Australian legume Castanospermum australe is also known to produce the same structural type of pyrrolizidines. There are reports of the isolation of australine (7a-epi-alexine) 2, 1-epi-australine 3, 3-epi-australine 4, and 7-epi-australine 5 from this plant to date. Their unambiguous syntheses established that the natural product reported as 5 is 2 and the published NMR data for 2 are those of 3. These confusions prompted us to unambiguously confirm the structures and biological activities of australine isomers and related alkaloids. A careful search for polyhydroxylated pyrrolizidines in seeds of C. australe led to the discovery of three new alkaloids, 2,3-diepi-australine 6, 2,3,7-triepi-australine 7, and the 2-O-β- d -glucopyranoside of 3 (8). Herein, we report the full 13C NMR assignment of alkaloids 1–8 and the glycosidase inhibitory activities of alkaloids 1–8 together with the highly oxygenated pyrrolizidine, casuarine 9, and its 6-O-α- d -glucopyranoside 10.
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Configurational and conformational analysis of highly oxygenated pyrrolizidines: definitive identification of some naturally occurring 7a-epi-alexines
Tetrahedron-asymmetry, 1998Co-Authors: Mark R. Wormald, Russell J. Molyneux, Robert J Nash, Peter Hrnciar, James D. White, George W J FleetAbstract:Abstract The NMR spectra of a number of naturally occurring alexines (tetrahydroxylated pyrrolizidine alkaloids) are analyzed and the consequences of changes in the configuration on the conformation of these bicyclic systems discussed. Unambiguous syntheses of australine (7-epi-alexine) and of 7,7a-epi-alexine have now unequivocally established the structures of two natural products isolated from Castanospermum australe which were insecure due to erroneous NMR data. Chemical shift parameters are unreliable as a method of comparing different samples of identical compounds; however, 1H–1H three bond coupling constants (3JHH) provide easy direct comparison between samples and allow assignments of both the relative configurations for the ring protons and the conformation of the pyrrolizidine framework.
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X-ray crystal structure of the hydrochloride of 6-epicastanospermine [(1S,6R,7R,8R,8aR)-1,6,7,8-tetrahydroxy-octahydroindolizine]
Phytochemistry, 1990Co-Authors: Robert J Nash, George W J Fleet, Linda E. Fellows, Aarti Girdhar, Josephine M. Peach, David J. Watkin, Mervyn P. HegartyAbstract:Abstract The X-ray crystal structure of the hydrochloride of 6-epicastanospermine [1 S ,6 R ,7 R ,8 R ,8 aR )-1,6,7,8-tetrahydroxyoctahydroindolizine], isolated from Castanospermum australe , is reported.
Russell J. Molyneux - One of the best experts on this subject based on the ideXlab platform.
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Phytochemicals: the good, the bad and the ugly?
Phytochemistry, 2007Co-Authors: Russell J. Molyneux, Kip E. Panter, Dale R Gardner, Lynn F. JamesAbstract:Phytochemicals are constitutive metabolites that enable plants to overcome temporary or continuous threats integral to their environment, while also controlling essential functions of growth and reproduction. All of these roles are generally advantageous to the producing organisms but the inherent biological activity of such constituents often causes dramatic adverse consequences in other organisms that may be exposed to them. Nevertheless, such effects may be the essential indicator of desirable properties, such as therapeutic potential, especially when the mechanism of bioactivity can be delineated. Careful observation of cause and effect, followed by a coordinated approach to identify the responsible entities, has proved extremely fruitful in discovering roles for phytochemical constituents. The process is illustrated by selected examples of plants poisonous to animals and include the steroidal alkaloid toxin of Veratrum californicum (Western false hellebore), piperidine alkaloids of Lupinus species (lupines), and polyhydroxy indolizidine, pyrrolizidine and nortropane alkaloids of Astragalus and Oxytropis species (locoweeds), Castanospermum australe (Moreton Bay chestnut) and Ipomoea species (morning glories).
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Australine and related alkaloids: easy structural confirmation by 13C NMR spectral data and biological activities
Tetrahedron-asymmetry, 2003Co-Authors: Atsushi Kato, Russell J. Molyneux, Robert J Nash, George W J Fleet, Mark R. Wormald, Isao Adachi, Erika Kano, Alison A. Watson, Haruhisa Kizu, Kyoko IkedaAbstract:Abstract The first polyhydroxylated pyrrolizidine alkaloid with a hydroxymethyl group at C-3 was isolated from pods of Alexa leiopetala (Leguminosae) and designated alexine 1. The Australian legume Castanospermum australe is also known to produce the same structural type of pyrrolizidines. There are reports of the isolation of australine (7a-epi-alexine) 2, 1-epi-australine 3, 3-epi-australine 4, and 7-epi-australine 5 from this plant to date. Their unambiguous syntheses established that the natural product reported as 5 is 2 and the published NMR data for 2 are those of 3. These confusions prompted us to unambiguously confirm the structures and biological activities of australine isomers and related alkaloids. A careful search for polyhydroxylated pyrrolizidines in seeds of C. australe led to the discovery of three new alkaloids, 2,3-diepi-australine 6, 2,3,7-triepi-australine 7, and the 2-O-β- d -glucopyranoside of 3 (8). Herein, we report the full 13C NMR assignment of alkaloids 1–8 and the glycosidase inhibitory activities of alkaloids 1–8 together with the highly oxygenated pyrrolizidine, casuarine 9, and its 6-O-α- d -glucopyranoside 10.
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Configurational and conformational analysis of highly oxygenated pyrrolizidines: definitive identification of some naturally occurring 7a-epi-alexines
Tetrahedron-asymmetry, 1998Co-Authors: Mark R. Wormald, Russell J. Molyneux, Robert J Nash, Peter Hrnciar, James D. White, George W J FleetAbstract:Abstract The NMR spectra of a number of naturally occurring alexines (tetrahydroxylated pyrrolizidine alkaloids) are analyzed and the consequences of changes in the configuration on the conformation of these bicyclic systems discussed. Unambiguous syntheses of australine (7-epi-alexine) and of 7,7a-epi-alexine have now unequivocally established the structures of two natural products isolated from Castanospermum australe which were insecure due to erroneous NMR data. Chemical shift parameters are unreliable as a method of comparing different samples of identical compounds; however, 1H–1H three bond coupling constants (3JHH) provide easy direct comparison between samples and allow assignments of both the relative configurations for the ring protons and the conformation of the pyrrolizidine framework.
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6,7-Diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase.
Biochemistry, 1991Co-Authors: Russell J. Molyneux, Joseph E Tropea, Gur P. Kaushal, Mabry Benson, Alan D ElbeinAbstract: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 {sup 1}H and {sup 13}C NMR spectra. The structure of the pyrrolidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal {alpha}-glucosidase, amyloglucosidase and a relatively weak inhibitor of {beta}-glucosidase. It failed to inhibit {alpha}-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.
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Analysis and distribution of swainsonine and related polyhydroxyindolizidine alkaloids by thin layer chromatography
Phytochemical Analysis, 1991Co-Authors: Russell J. Molyneux, Lynn F. James, Kip E. Panter, Michael H. RalphsAbstract:A spray reagent which is sensitive and specific for polyhydroxyindolizidine glycosidase inhibitors such as swainsonine and castanospermine has been developed for their visualization on thin layer chromatographic plates. The method involves treatment of the plates with a sequential system consisting of 10% acetic anhydride in benzene, followed by Ehrlich's reagent. This technique has been used to follow the isolation and purification of minor alkaloidal constituents from Astragalus lentiginosus and Castanospermum australe. The occurrence of swainsonine and its N-oxide in a number of Astragalus and Oxytropis species has been investigated. Species previously incriminated as locoweeds on the basis of field observations were all shown to contain the alkaloid and it was also found to occur in additional species. The highest levels of swainsonine were found in the seeds and pods, with lesser amounts in the leaves and stems, and none detectable in the roots.
George W J Fleet - One of the best experts on this subject based on the ideXlab platform.
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isolation of the pyrrolizidine alkaloid 1 epialexine from Castanospermum australe
Phytochemistry Letters, 2010Co-Authors: Laurence Edmund Jones, George W J Fleet, David J. Watkin, Jacqueline Hollinshead, Amber L Thompson, Sarah F Jenkinson, Atsushi Kato, Robert J NashAbstract:Abstract The Australian leguminous tree Castanospermum australe contains the anti-viral glucose analogue indolizidine alkaloid castanospermine. As the result of a search for new bioactive carbohydrate-like compounds we now report the isolation of the novel polyhydroxylated pyrrolizidine alkaloid, 1-epialexine, from the leaves and stems of C. australe. 1-Epialexine is a weak inhibitor of β-mannosidase from Cellullomonas fimi.
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Australine and related alkaloids: easy structural confirmation by 13C NMR spectral data and biological activities
Tetrahedron-asymmetry, 2003Co-Authors: Atsushi Kato, Russell J. Molyneux, Robert J Nash, George W J Fleet, Mark R. Wormald, Isao Adachi, Erika Kano, Alison A. Watson, Haruhisa Kizu, Kyoko IkedaAbstract:Abstract The first polyhydroxylated pyrrolizidine alkaloid with a hydroxymethyl group at C-3 was isolated from pods of Alexa leiopetala (Leguminosae) and designated alexine 1. The Australian legume Castanospermum australe is also known to produce the same structural type of pyrrolizidines. There are reports of the isolation of australine (7a-epi-alexine) 2, 1-epi-australine 3, 3-epi-australine 4, and 7-epi-australine 5 from this plant to date. Their unambiguous syntheses established that the natural product reported as 5 is 2 and the published NMR data for 2 are those of 3. These confusions prompted us to unambiguously confirm the structures and biological activities of australine isomers and related alkaloids. A careful search for polyhydroxylated pyrrolizidines in seeds of C. australe led to the discovery of three new alkaloids, 2,3-diepi-australine 6, 2,3,7-triepi-australine 7, and the 2-O-β- d -glucopyranoside of 3 (8). Herein, we report the full 13C NMR assignment of alkaloids 1–8 and the glycosidase inhibitory activities of alkaloids 1–8 together with the highly oxygenated pyrrolizidine, casuarine 9, and its 6-O-α- d -glucopyranoside 10.
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Configurational and conformational analysis of highly oxygenated pyrrolizidines: definitive identification of some naturally occurring 7a-epi-alexines
Tetrahedron-asymmetry, 1998Co-Authors: Mark R. Wormald, Russell J. Molyneux, Robert J Nash, Peter Hrnciar, James D. White, George W J FleetAbstract:Abstract The NMR spectra of a number of naturally occurring alexines (tetrahydroxylated pyrrolizidine alkaloids) are analyzed and the consequences of changes in the configuration on the conformation of these bicyclic systems discussed. Unambiguous syntheses of australine (7-epi-alexine) and of 7,7a-epi-alexine have now unequivocally established the structures of two natural products isolated from Castanospermum australe which were insecure due to erroneous NMR data. Chemical shift parameters are unreliable as a method of comparing different samples of identical compounds; however, 1H–1H three bond coupling constants (3JHH) provide easy direct comparison between samples and allow assignments of both the relative configurations for the ring protons and the conformation of the pyrrolizidine framework.
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X-ray crystal structure of the hydrochloride of 6-epicastanospermine [(1S,6R,7R,8R,8aR)-1,6,7,8-tetrahydroxy-octahydroindolizine]
Phytochemistry, 1990Co-Authors: Robert J Nash, George W J Fleet, Linda E. Fellows, Aarti Girdhar, Josephine M. Peach, David J. Watkin, Mervyn P. HegartyAbstract:Abstract The X-ray crystal structure of the hydrochloride of 6-epicastanospermine [1 S ,6 R ,7 R ,8 R ,8 aR )-1,6,7,8-tetrahydroxyoctahydroindolizine], isolated from Castanospermum australe , is reported.
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two alexines 3 hydroxymethyl 1 2 7 trihydroxypyrrolizidines from Castanospermum australe
Phytochemistry, 1990Co-Authors: Robert J Nash, George W J Fleet, Linda E. Fellows, Aarti Girdhar, Josephine M. Peach, Janet V. Dring, Nigel RamsdenAbstract: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.
Alan D Elbein - One of the best experts on this subject based on the ideXlab platform.
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The Effects of Castanospermine and Swainsonine on the Activity and Synthesis of Intestinal Sucrase
Archives of Biochemistry and Biophysics, 1993Co-Authors: J. Ghidoni, Alan D ElbeinAbstract:Abstract Castanospermine is an indolizidine alkaloid that is found in the seeds of the Australian tree Castanospermum australe . These seeds have been reported to be toxic to animals and to cause severe gastrointestinal upset. In order to determine whether castanospermine is responsible for this toxicity, the alkaloid was injected into young mice or rats, and its effects on various intestinal disaccharidases were determined. Another indolizidine alkaloid, the α-mannosidase inhibitor swainsonine, was also tested to compare its effects to those of castanospermine. Castanospermine strongly and rapidly inhibited the activity of the disaccharidases, sucrase, maltase, and trehalase, with sucrase being the most sensitive to inhibition. The loss of activity of these enzymes, especially sucrase, in injected animals appeared to be due to a direct inhibition of enzyme activity, rather than to a change in the structure of the glycan chains of the enzyme, since only minor alterations in carbohydrates were observed. On the other hand, swainsonine, when injected into animals, also profoundly decreased the activity of the sucrase, but this alkaloid had no direct effect on sucrase activity although it did markedly alter the carbohydrate nature of this glycoprotein. This change in oligosaccharide structure may affect protein conformation, stability, or targeting, any or all of which may in turn affect activity. In in vitro studies with the purified enzyme, castanospermine was found to be a competitive inhibitor of intestinal sucrase, but it was a noncompetitive inhibitor of intestinal maltase. A number of other glucosidase inhibitors that inhibit sucrase activity in vitro are also described.
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6,7-Diepicastanospermine, a tetrahydroxyindolizidine alkaloid inhibitor of amyloglucosidase.
Biochemistry, 1991Co-Authors: Russell J. Molyneux, Joseph E Tropea, Gur P. Kaushal, Mabry Benson, Alan D ElbeinAbstract: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 {sup 1}H and {sup 13}C NMR spectra. The structure of the pyrrolidine alkaloids which co-occur in C. australe. 6,7-Diepicastanospermine was found to be a moderately good inhibitor of the fungal {alpha}-glucosidase, amyloglucosidase and a relatively weak inhibitor of {beta}-glucosidase. It failed to inhibit {alpha}-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.
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7 deoxy 6 epi castanospermine a trihydroxyindolizidine alkaloid glycosidase inhibitor from Castanospermum australe
Journal of Natural Products, 1990Co-Authors: Russell J. Molyneux, Joseph E Tropea, Alan D ElbeinAbstract:: A new indolizidine alkaloid has been isolated from the seeds of Castanospermum [1] australe and identified as 7-deoxy-6-epi-castanospermine by ms and 1H- and 13C-nmr spectroscopy. The alkaloid is the first trihydroxylated indolizidine to be isolated from this plant and may represent an intermediate in the biosynthetic pathway to the tetrahydroxy-indolizidines and -pyrrolizidines. It inhibits amyloglucosidase and yeast alpha-glucosidase but is significantly less active as a glycosidase inhibitor than its isomer swainsonine [2] and the tetrahydroxylated alkaloids castanospermine [3], 6-epi-castanospermine [4], and australine [5].