Species difference in the urinary excretion of isatinecic acid from the pyrrolizidine alkaloid retrorsine.

1. The urinary excretion of the metabolites, isatinecic acid and pyrrolic metabolites from the pyrrolizidine alkaloid retrosine were lower in the resistant species, guinea-pigs, than the susceptible species, mice, hamsters and rats. 2. The urinary N-oxides levels, however, were higher in guinea-pigs relative to mice, hamsters and rats. 3. These results conform to the postulate that a common metabolic pathway exists between the formation of isatinecic acid and pyrrolic metabolites. 4. The resistance of guinea-pigs to PA poisoning is attributed to the high metabolism of PAs to N-oxides combined with a corresponding low conversion to pyrrolic metabolites.     

Species differences in the hepatic microsomal metabolism of the pyrrolizidine alkaloid senecionine

1. The comparative metabolism of the pyrrolizidine alkaloid (PA) senecionine was studied in vitro in incubations of rat, guinea pig, cow, horse, and sheep hepatic microsomes. 2. Levels of the toxic pyrrolic metabolite 6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) were higher from guinea pig incubations (39.9 nmol/mg protein) than from other species (range 0.07 to 7.5 nmol/mg); results disagree with prior studies which used nonspecific techniques and suggest that the guinea pig's resistance to certain PAs may be due to resistance to pyrrole toxicity rather than low pyrrole formation. 3. Minor differences in senecionine N-oxidation and hydrolysis existed between the various species.     

Novel pyrrolizidine alkaloid from Crotalaria nana

Crotananine, isolated from the seeds of Crotalaria nana has been shown by spectroscopy and chemical evidence to be the macrocyclic diester of retronecine and a new C₉ necic acid, crotananic acid.     

Isolation of the pyrrolizidine alkaloid 1-epialexine from Castanospermum australe

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.     

Helifoline,a pyrrolizidine alkaloid from Heliotropium ovalifolium

The alkaloidal fraction of Heliotropium ovalifolium yielded retronecine and the new pyrrolizidine alkaloid helifoline. Helifoline was formulated as 1α-angelyloxymethyl-8α-pyrrolizidine-2β,7β-diol on the basis of spectroscopic measurements and hydrolysis to the necine base which appears to be identical with croalbinecine.     

Uspallatine,a pyrrolizidine alkaloid from senecio uspallatensis

A new pyrrolizidine alkaloid uspallatine was isolated from roots of Senecio uspailatensis together with the previously known retrorsine. The structure of the new alkaloid was established by spectroscopical data and chemical transformation.     

Biliary excretion in foreign compounds. Species difference in biliary excretion

1. The biliary excretion of injected [¹⁴C]aniline, [¹⁴C]benzoic acid, 4-amino-hippuric acid and 4-acetamidohippuric acid in six or eight species of animal (rat, dog, hen, cat, rabbit, guinea pig, rhesus monkey and sheep) was studied. 2. These compounds, with molecular weights in the range 93–236, are poorly excreted in the bile in all the species examined and, in effect, there is little significant species difference in the extent of their biliary excretion. 3. Compounds of higher molecular weight (355–495) were also studied, namely succinylsulphathiazole, [¹⁴C]stilboestrol glucuronide, sulphadimethoxine N¹-glucuronide and phenolphthalein glucuronide. 4. With these compounds a clear species difference in the extent of biliary excretion was found, the rat, dog and hen being good excretors, the rabbit, guinea pig and monkey poor excretors, and the cat and sheep taking an intermediary position. 5. There was a general trend for biliary excretion to be higher in all species when the compounds were of higher molecular weight. 6. These results are discussed in their relation to species differences in drug metabolism.     

Selective uptake of pyrrolizidine N-oxides by cell suspension cultures from pyrrolizidine alkaloid producing plants

The N-oxides of pyrrolizidine alkaloids such as senecionine or monocrotaline are rapidly taken up and accumulated by cell suspension cultures obtained from plants known to produce pyrrolizidines, i.e. Senecio vernalis, vulgaris, viscosus (Asteraceae) and Symphytum officinale (Boraginaceae). The transport of the N-oxides into the cells is a specific and selective process. Other alkaloid N-oxides such as sparteine N-oxide are not taken up. Cell cultures from plant species which do not synthesize pyrrolizidine alkaloids are unable to accumulate pyrrolizidine N-oxides. The suitability of the pyrrolizidine N-oxides in alkaloid storage and accumulation is emphasized.     

Absolute configuration of the pyrrolizidine alkaloid acetylgynuramine

The absolute configuration of the pyrrolizidine alkaloid acetylgynuramine was determined by X-ray diffraction to be (?)-(1aR,6bR,10R,11S)-9,14-dioxo-10-hydroxy-13-cis-ethylidene-11-methoxyacetyl-10-methyl-1a,2,3,6b-tetrahydro-5H-pyrrolizino-(1a,6b,6a,b,c)-1,8-dioxa-cyclododecane.     

Ehretinine,a novel pyrrolizidine alkaloid from Ehretia aspera

The structure for ehretinine, 7-O-(p-methoxybenzoyl)-retronecanol, a new pyrrolizidine alkaloid isolated from leaves of Ehretia aspera has been established by a combination of spectroscopic and chemical methods. To our knowledge this constitutes the first report of the natural occurrence of a retronecanol ester.     

Globiferine a pyrrolizidine alkaloid from crotalaria globifera

Seeds of Crotalaria globifera from two separate locations in South Africa yielded different pyrrolizidine alkaloids. One batch gave trichodesmine and grantaline, while the other afforded grantianine and a new pyrrolizidine alkaloid, globiferine.     

Structure revision of emiline a pyrrolizidine alkaloid from Emilia flammea

The structure of emiline, a pyrrolizidine alkaloid isolated fromEmilia flammea has been revised from an 11-membered alkaloid to a 12-membered macrocyclic diester containing otonecine.     

Variation in pyrrolizidine alkaloid patterns of Senecio jacobaea

We studied the variation in pyrrolizidine alkaloid (PA) patterns of lab-grown vegetative plants of 11 European Senecio jacobaea populations. Plants were classified as jacobine, erucifoline, mixed or senecionine chemotypes based on presence and absence of the PAs jacobine or erucifoline. Due to the presence of jacobine, total PA concentration in jacobine chemotypes was higher than in erucifoline chemotypes. Both relative and absolute concentrations of individual PAs differed between half-sib and clonal families, which showed that variation in PA patterns had a genetic basis. Within most populations relative abundance of PAs varied considerably between individual plants. Most populations consisted either of the jacobine chemotype or of the erucifoline chemotype, sometimes in combination with mixed or senecionine chemotypes.     

Thesinine-4'-O-beta-D-glucoside the first glycosylated plant pyrrolizidine alkaloid from Borago officinalis

The glycosylated pyrrolizidine alkaloid, thesinine-4'-O-beta-D-glucoside, has been isolated from the aqueous methanol extract of dried, defatted seeds of Borago officinalis (Boraginaceae). The structure was established by means of spectroscopic and chemical analysis.