Pyrrolizidine alkaloids from Echium glomeratum (Boraginaceae)

The methanolic extract of the whole plant of Echium glomeratum Poir. (Boraginaceae) has afforded five pyrrolizidine alkaloids, three that were (7S, 8R)-petranine (1), (7S, 8S)-petranine (2), and (7R, 8R)-petranine (3a) or (7R, 8S)-petranine (3b), comprising a tricyclic pyrrolizidine alkaloids subclass; and two that were known but to the species: 7-angeloylretronecine (4) and 9-angeloylretronecine (5). All compounds were tested against a human tumor panel for cytotoxicity; no activity was observed (EC(50) values>20mug/ml).     

Pyrrolizidine alkaloids from Anchusa strigosa and their antifeedant activity

The pyrrolizidine alkaloid (PA) content of flowers, leaves, and roots of Anchusa strigosa (Boraginaceae) was analysed by ESI-LC-MS. Six PAs, including two new natural compounds, were detected, characterized by NMR spectroscopy, and quantified in each plant organ. The results indicated that the highest total concentration of PAs was in the leaves (23.63 mg/g of dried part), followed by the flowers (19.77 mg/g), and finally by the roots (1.80 mg/g). All PAs isolated were subjected to Spodoptera exigua and Pieris brassicae larvae. Feeding activity by both herbivore species using a bioassay was inhibited up to circa 75% depending on PA and applied concentration.     

Pyrrolizidine alkaloids from Alkanna tinctoria

Three pyrrolizidine alkaloids were isolated from Alkanna tinctoria and their structures analysed by spectroscopic methods. One of them is new and the name dihydroxytriangularine is proposed for it.     

Pyrrolizidine alkaloids in the antipodean genus Brachyglottis (Asteraceae)

The phylogeny of the genus Brachyglottis suggests that its constituent species should contain pyrrolizidine alkaloids. Consistent with this hypothesis, and the established occurrence of such alkaloids in Brachyglottis repanda, Brachyglottis kirkii, and Brachyglottis hectori, an investigation of Brachyglottis adamsii revealed the presence of senecionine and retrorsine; Brachyglottis huntii was found to contain senkirkine and retrorsine; 7-O-angelylheliotridine was the predominant alkaloid in Brachyglottis perdicioides, and the same alkaloid together with senecionine, senkirkine and intergerrimine was present in the Brachyglottis hectori × B. perdicioides “Alfred Atkinson” horticultural hybrid; Brachyglottis sciadophila contained clivorine and neopetasitenine (acetylfukinotoxin); the latter alkaloid was also present in B. kirkii together with the previously reported senkirkine and senkirkine 12-acetate.     

Pyrrolizidine alkaloids in and on the leaf surface of Senecio jacobaea L

This is the first study showing that alkaloids are present on the leaf surface of plants. A concentration of 30-230 pmol/cm2 pyrrolizidine alkaloids (PA's) was detected in 8 different samples taken from Senecio jacobaea. PA concentration on the leaves was marginally correlated with PA concentration of the total leaf tissues. The PA spectrum on the leaf differed from the PA spectrum of the total leaf.     

Pyrrolizidine alkaloids from Senecio cacaliaster

Four pyrrolizidine alkaloids have been isolated from Senecio cacaliaster and their structures analysed by spectroscopic methods (IR, mass, ¹H, ¹³CNMR). One of them is new and the name sencalenine (3) is proposed. Alkaloids O⁷-senecioylretronecine (1) and 7-senecioyl-9-sarracinylretronecine (2) have recently been identified elsewhere. The fourth is bulgarsenine (4) which was isolated from a Senecio species before.     

Pyrrolizidine alkaloids from Canarian endemic plants and their biological effects

Pyrrolizidine alkaloid (PA) producing plants belonging to the Boraginaceae (Echium wildpretti) and Asteraceae (Canariothamnus palmensis, Kleinia neriifolia, Pericallis appendiculata, Pericallis echinata, Pericallis hansenii, Pericallis multiflora, Pericallis steetzii and Senecio bollei) were selected to study their alkaloidal composition and the defensive properties (antifeedant and phytotoxic effects) of their ethanolic and alkaloidal extracts plus their isolated PAs against insects (Spodoptera littoralis, Leptinotarsa decemlineata, the aphids Myzus persicae and Rhopalosiphum padi) and Lactuca sativa seeds. We also tested the selective cytotoxic effects of these PAs on insect-derived Sf9 and mammalian CHO cells. Most of the insect antifeedant effects were found in the ethanolic extracts. The isolated PAs had species- and structure-dependent antifeedant effects and all of them decreased L. sativa radicle growth, suggesting a specific mode of action against insects and a generalized one against plants. Given the relatively low alkaloid content of these species, we assume that their herbivore defenses are not only alkaloid-based.     

Pyrrolizidine alkaloids from seeds of Crotalaria scassellatii

Three pyrrolizidine alkaloids were isolated from the seeds of Crotalaria scassellatii. Axillaridine and axillarine were the two major alkaloids whereas the third minor alkaloid was a new compound. Its structure was determined as desoxyaxillarine.     

Pyrrolizidine alkaloids of the endemic Mexican genus Pittocaulon and assignment of stereoisomeric 1,2-saturated necine bases

The endemic Mexican genus Pittocaulon (subtribe Tussilagininae, tribe Senecioneae, Asteraceae) belongs to a monophyletic group of genera distributed in Mexico and North America. The five Pittocaulon species represent shrubs with broom-like succulent branches. All species were found to contain pyrrolizidine alkaloids (PAs). With one exception (i.e., stems of Pittocaulon velatum are devoid of PAs) PAs were found in all plant organs with the highest levels (up to 0.3% of dry weight) in the flower heads. Three structural types of PAs were found: (1) macrocyclic otonecine esters, e.g. senkirkine and acetylpetasitenine; (2) macrocyclic retronecine esters, e.g. senecionine, only found in roots, and (3) monoesters of 1,2-saturated necines with angelic acid. For an unambiguous assignment of the different stereoisomeric 1,2-saturated necine bases a GC-MS method was established that allows the separation and identification of the four stereoisomers as their diacetyl or trimethylsilyl derivatives. All otonecine esters that generally do not form N-oxides and the 1,2-saturated PAs were exclusively found as free bases, while the 1,2-unsaturated 7-angeloylheliotridine occurring in P. velatum was found only as its N-oxide. In a comparative study the 1H and 13C NMR spectra of the four stereoisomeric necine bases were completely assigned by the use of DEPT-135, H,H-COSY, H,C-HSQC and H,H-NOESY experiments and by iterative analysis of the 1H NMR spectra. Based on these methods the PA monoesters occurring in Pittocaulon praecox and P. velatum were assigned as 7-O-angeloyl ester respectively 9-O-angeloyl ester of dihydroxyheliotridane which could be identified for the first time as naturally occurring necine base. Unexpectedly, in the monoesters isolated from the three other Pittocaulon species dihydroxyheliotridane is replaced by the necine base turneforcidine with opposite configuration at C-1 and C-7. The species-specific and organ-typical PA profiles of the five Pittocaulon species are discussed in a biogenetic context.     

Chemical constituents from Stenosolenium saxatile (Pall.) Turcz. (Boraginaceae)

Chemical investigation on the whole plants of Stenosolenium saxatile led to the isolation of three naphthoquinones (1–3), five pyrrolizidine alkaloids (PAs) (4–8), and six phenolic acids (9–14). The structure of the isolated compounds was elucidated by different spectrometric methods (¹H NMR, ¹³C NMR and ESI-MS). These results are the first chemical data on constituents of this genus. The chemotaxonomic relationships between the genera Stenosolenium, Onosma, Arnebia, Echium and Lithospermum are also discussed.     

Emiline,a new alkaloid from the aerial parts of Emilia sonchifolia

A new pyrrolidine alkaloid, Emiline (1), was isolated from the 90% EtOH extract of the aerial parts of Emilia sonchifolia. Its structure was established by various spectroscopic methods, including NMR, IR, HR-ESI-MS and X-ray crystallography. It was characterized by its skeleton derived from a bicyclo-[2.2.2]-oct-5-one ring and a pyrrolidine unit. The racemic mixture, (±)-Emiline, displayed good neuroprotective effect against the corticosterone-induced apoptosis in PC12 cells.     

Bishordeninyl terpene alkaloids and other constituents of Zanthoxylum culantrillo and Z. coriaceum

A new alkaloid, culantraramine, has been found in Zanthoxylum culantrillo, and the known alkaloid, alfileramine, has been identified from Z. coriaceum. Both alkaloids are members of a new structural type, bishordeninyl terpenes. Z. culantrillo was also found to contain eudesmin, epieudesmin, hordenine, N-methylisocorydine, magnoflorine, candicine, skimmianine, synephrine, tembetarine and a dihydroxy-dimethoxytetrahydroprotoberberine. Isolated from Z. coriaceum were N-methylisocorydine, dihydrochelerythrine, chelerythrine, N-methylcanadine and aegiline, in addition to alfileramine.     

Physicochemical and metabolic basis for the differing neurotoxicity of the pyrrolizidine alkaloids,trichodesmine and monocrotaline

Monocrotaline and trichodesmine are structurally closely related pyrrolizidine alkaloids (PAs) exhibiting different extrahepatic toxicities, trichodesmine being neurotoxic (LD₅₀ 57 μmol/kg) and monocrotaline pneumotoxic (LD₅₀ 335 μmol/kg). We have compared certain physicochemical properties and metabolic activities of these two PAs in order to understand the quantitative and qualitative differences in toxicity. Both PAs were metabolized in the isolated, perfused rat liver to highly reactive pyrrolic dehydroalkaloids that appear to be responsible for the toxicity of PAs. More dehydrotrichodesmine (468 nmol/g liver) than dehydromonocrotaline (116 nmol/g liver) was released from liver into perfusate on perfusion for 1 hr with 0.5 mM of the parent PA. Dehydrotrichodesmine had a significantly longer aqueous half-life (5.4 sec) than that of dehydromonocrotaline (3.4 sec). In vivo, significantly higher levels of bound pyrroles were found in the brain 18 hr after injection of trichodesmine (25 mg/kg; i.p) than were seen following either an equal dose (25 mg/kg; i.p.) or an equitoxic dose (90 mg/kg; i.p.) of monocrotaline. Trichodesmine had a higher partition coefficient than monocrotaline for both chloroform and heptane, indicating its greater lipophilicity. The pK_a of trichodesmine (7.07) was only slightly higher than that of monocrotaline (pK_a 6.83), suggesting that a difference in degree of ionization was not a major factor affecting the relative ability of the dehydroalkaloids to cross the blood-brain barrier. We conclude that the greater lethality and neurotoxicity of trichodesmine compared to monocrotaline is due to two structural characteristics: (i) steric hindrance at position 14 of dehydrotrichodesmine results in greater resistance to hydrolysis, allowing more to be released from the liver and to be delivered to the brain; (ii) the larger isopropyl substituent at position 14 of dehydrotrichodesmine renders the molecule more lipophilic, leading to greater penetration of the brain. Special issue dedicated to Dr. Kinya Kuriyama     

Pyrrolizidine alkaloids of Heliotropium from Mexico and adjacent U.S.A.

The levels of alkaloids were determined in leaves and stems of 24 species of Heliotropium collected in Mexico and adjacent U.S.A. All species contained unsaturated pyrrolizidines, their content in leaves ranging from 0.003 to 0.18%. Saturated pyrrolizidine alkaloids were detected in nine species. Greenhouse-grown plants of five species had a significantly higher alkaloid content in their leaves than the corresponding field samples. In all these species, except for H. indicum, the differences were due to higher levels of saturated pyrrolizidines.     

Dehydroisostrychnobiline,matopensine and other alkaloids from Strychnos kasengaensis

Eighteen alkaloids have been identified in the root bark, stem bark and leaves of Strychnos kasengaensis from Zaire, They are isoretulinal, retuline, desacetyl isoretuline, desacetyl retuline, dehydroisostrychnobiline, matopensine and its mono-N-oxide, nordihydrotoxiferine, isoretuline, N(1)-desacetyl 18-acetoxyisoretuline, Wieland-Gumlich aldehyde and diol, desacetyl isoretulinal, O-acetyl retuline, 16R-isositsirikine, O-acetyl isoretuline, 11-methoxy retuline and 11-methoxy isoretuline.     

Aporphinoid alkaloids and other constituents from Lettowianthus stellatus

Two new aporphinoid alkaloids, f1ttowianthine and 11-methoxylettowianthine were isolated from the root bark of Lettowianthus stellatus, together with the new sesquiterpene 11-hydroxyguaia-4,6-diene and the known compounds liriodenine, (Z)-7-octadecen-9-ynoic acid, methyl (2E,6E,10R)-10,11-epoxy-3,7,11-trimethyl-2,6-dodecadienoate, methyl (2E,6E,10R)-10,11-dihydroxy-3,7,11-trimethyl-2,6-dodecadienoate , and 3,4,5-trimethoxyphenol. The structure elucidation was achieved by spectroscopic methods.