C. C. J. Culvenor's research while affiliated with La Trobe University and other places

Publications (73)

Article
The absolute structure of latifoline, a pyrrolizidine diester alkaloid of retronecine and latifolic and angelic acids, has been defined by single-crystal X-ray crystallographic analysis of the hydrobromide salt hydrate. Orthorhombic crystals of C20H27NO7.HBr.H2O belong to the space group P 2′2′2′ with a 7.279(1), b 17.898(3), c 17.922(2) Å and V 23...
Article
The supposed non-pyrrolizidine compound prepared from senkirkine and chloroplatinic acid, and thought to be a reaction product or an impurity in the senkirkine, is shown to be senkirkine chloroplatinate by a reprocessing of the crystallographic data.
Article
Phomopsin A, C36H45CIN6O12, the main mycotoxin isolated from cultures of Phomopsis leptostromiformis and the cause of lupinosis disease, is a linear hexapeptide containing 3-hydroxy-L-isoleucine, 3,4-didehydrovaline, N-methyl-3-(3-chloro-4,5-dihydroxyphenyl)serine, E-2,3-didehydroaspartic acid, E-2,3-didehydroisoleucine, and 3,4-didehydro-L-proline...
Article
An alkaloid which was previously isolated from Crotalaria crispata and reported as crispatine despite data differing from that for the original crispatine (I) is reexamined.
Article
Quantitative toxicity studies were carried out in sheep using corynetoxin, tunicamycin and toxic annual ryegrass (Lolium rigidurri). Sheep were very sensitive to these toxins. The lethal dose was about 35 μ.g/kg bodyweight for pure tunicamycin given by subcutaneous injection and 3 to 5 mg/kg for corynetoxin administered orally as slurries of bacter...
Article
Phomopsins comprise a family of peptide mycotoxins containing a 13-membered ring formed by an ether bridge, produced by the fungus Phomopsis leptostromiformis, the causal agent in lupin poisoning (lupinosis). The biochemical actions of two naturally occurring phomopsins, phomopsin A and B, and the chemical derivatives, phomopsinamine A and octahydr...
Article
A crystallographic study of phompsin A, the hexapeptide mycotoxin of Phomopsis leptostromiformis responsible for lupinosis disease in animals, has shown that it is a linear peptide, modified by an ether bridge in place of the hydroxy groups of the N-methyl-3-(3-chloro-4,5-dihydroxyphenyl)-3-hydroxyalanine and 3-hydroxyisoleucine units, and thus con...
Article
The presence of toxic pyrrolizidine alkaloids in several prolific Australian weeds presents a health hazard to both livestock and humans. Their toxicity is dependent on metabolic activation giving reason to think that they have evolved as relatively inert compounds which can be mobilized at short notice as cytotoxic agents to repel microbes. In thi...
Article
Characterization data are presented for grantianine and grantaline, alkaloids of Crotalaria virgulata subsp. grantiana. The plant growing in Australia also contains 1-hydroxymethyl-1β,2β-epoxy-8αH-pyrrolizidine.
Article
Full-text available
La crispatine a ete isolee avec la fulvine et la monocrotaline de Crotalaria crispata (famille Leguminosae). Cristallisation dans P1 avec Z=1; affinement jusqu'a R=0,037. La conformation du macrocyle a 11 membres est semblable a celle qui a ete observee dans la monocrotaline et la fulvine. Le substituant OH forme une liaison hydrogene intramolecula...
Article
Pyrrolizidine alkaloid poisoning in humans is associated with the consumption of plants containing the alkaloids, either as contaminants of grains or as infusions for medicinal purposes. The alkaloids are carcinogenic in rats but have not been associated, so far, with tumors in humans. For the known instances of human intake of pyrrolizidine alkalo...
Article
Phomopsin A, the main mycotoxin isolated from cultures of Phomopsis leptostromiformis and the cause of lupinosis disease in animals grazing infected lupins, is a cyclic hexapeptide containing 3-hydroxyisoleucine, 3,4-didehydrovaline, N-methyl-3-(3-chloro-4,5-dihydroxyphenyl)-3-hydroxyalanine, E-2,3-didehydroaspartic acid, E-2,3-didehydroisoleucine,...
Article
The corynetoxins, formed in galled seeds of Lolium rigidum(annul ryegrass) occupied by Corynebacterium rathayi and responsible for annual ryegrass toxicity, are identified as new members of the tunicamycin group of antibiotics.
Article
Full-text available
A group of highly toxic compounds was isolated from galled seedheads of annual ryegrass (Lolium rigidum Gaud.) containing Corynebacterium rathayi. Purified extracts were resolved by reverse-phase high-performance liquid chromatography into eight main fractions which have been partially characterised and shown to be toxic to nursling rats. A mixture...
Article
Summary The isolation of crystalline intermedine fromConoclinium, coelestinum (L.) DC., notmixed with the diastereoisomeric congener base lycopsamine, is reported.E. compositifolium Walt. yielded the usual mixture of intermedine and lycopsamine; fromE. altissimum L. rinderine and 7-angelylheliotridine have been isolated.
Article
Callimorphine, a putative pyrrolizidine alkaloid metabolite found in some Arctiid moths which feed as larvae on plants containing pyrrolizidine alkaloids, has been identified and synthesised.
Article
Intermedine and lycopsamine are diastereoisomers containing vicinal glycol groups of different configuration. The difference in the degree to which they complex with borate is the basis of two procedures for their separation from mixtures on a preparative scale. In the first, the mixture dissolved in chloroform is passed through a column of glass p...
Article
Eight pyrrolizidine alkaloids of hepatotoxic type have been indentified in leaves of Symphytum X uplandicum. The combined alkaloids exhibit chronic hepatotoxicity in rats.
Article
Phomopsin A, the main toxic metabolite of Phomopsis leptostromiformis responsible for lupinosis, has an empirical formula approximately C33H44N5O13Cl. There are 3 acidic centers per molecule which are probably phenolic, β-diketone or ββ-triketone in nature. Ultraviolet, infrared, and nuclear magnetic resonance spectra are described. These and the m...
Chapter
Aqueous acetone extraction of toxic seedheads of Lolium rigidum infested with the nematode Anguina lolii and Corynebacterium sp., probably C. rathayi, leads to a toxic precipitate, insoluble in water at pH 3.5. Partial purification of the toxin, which is retained on an XM-300 membrane with nominal cut-off at 300,000 mol. wt., is described. Despite...
Chapter
Investigations into the protection of sheep from poisoning by Heliotropium europaeum are summarized. Inhibition of methanogenesis in the sheep rumen by means of iodoform, designed to increase conversion of alkaloids into 1-methylenepyrrolizidine derivatives, gives a small degree of protection. Manipulation of liver enzyme levels by induction and in...
Article
Curassavine, the major alkaloid of Heliotropium curassavicum Linn. is shown to be an ester of trachelanthamidine with 3-carboxy-4-methylhexane-2,3-diol (homoviridifloric acid), the first example of a monocarboxylic necic acid with a C8 skeleton; the minor alkaloids, coromandalin and heliovicine are esters of trachelanthamidine with (+)-viridifloric...
Article
Two metabolites of P. leptostromiformis (phomopsins A and B) have been isolated as a crystalline mixture from a culture of the fungus on lupin seed. The mixture has been shown to be capable of inducing lupinosis in sheep and in young rats. Key steps in the isolation were the transfer of the phomopsins from crude aqueous solution to tetrahydrofuran...
Article
Adult male Ithomiinae feed at plants containing pyrrolizidine alkaloids. Certain species secrete on hairs of the costal fringe, a specialized organ on their hindwings, a novel -lactone structurally related to the unusual branched-chain acids that are unique to these alkaloids.
Article
The plantHeliotropium indicum L. (Boraginaceae) contains pyrrolizidine alkaloids. When dried, it is a powerful attractant for male ithomiine and danaine butterflies, which congregate and feed at its dead shoots. The butterflies use alkaloids derived from the plants for the formation of chemicals with pheromone/allomone activity. Baiting with alkalo...
Article
62 pyrrolizidine alkaloids and derivatives have been screened for acute and chronic hepato- and pneumotoxicity by the single dose method previously described. This procedure is satisfactory for the compounds of medium to high hepatotoxicity but failed to detect toxicity in certain other compounds of known, low hepatotoxicity. New findings significa...
Article
Il a t montr que deux espces deParsonsia (famille Apocynaceae), qui attirent les papillons mles de la sous-famille Danainae, contiennent des alcalodes du type 1,2-dehydropyrrolizidine, trouvs jusqu' prsent seulement chez les Boraginaceae.
Article
MALE butterflies of the nymphalid subfamily Danainae possess pheromone disseminating organs (hairpencils) the secretions of which function as female flight arrestants or aphrodisiacs1,2 and in some case as female attractants1. The hairpencil secretions of a number of Danaid species contain dihydropyrrolizine derivatives3-8 which are obtained from p...
Article
Die Duftorgane der mnnlichen BrenspinnerUtetheisa pulchelloides undU. lotrix (Fam. Arctiidae) scheiden Dihydropyrrolizine aus, die im Typ den Pheromonen von Schmetterlingen der Subfamilie Danainae (Fam. Papilionidae) gleichen. Wahrscheinlich handelt es sich um Derivate von Pyrrolizidin-Alkaloiden, die in den Wirtsplanzen der Raupen in hoher Konzent...
Article
Von 6 australischen Schmetterlingsarten der Untergruppe Danainae enthielten 4 Dihydropyrrolizine, dazu das bekannte Keton (I) und 2 verwandte Substanzen (II and III).
Article
In otonecine esters, the pyrrolizidine nucleus is so modified (strictly, they are pyrrolizidine derivatives only when proton-ated) that they are not obviously capable of yielding pyrrolic metabolites. We have shown, however, that otosenine (I), another ester of otonecine and also hepatotoxic (in spite of Vanek's report4), gives pyrrolic metabolites...
Article
Die 1,2-Doppelbindung des Monocrotalins (I) wird durch gebräuchliche Oxidantien, wie z.B. Trifluoressigsäureanhydrid (TFEA) in Chloroform nicht angegriffen; dabei entsteht bei -5°C (70 Std.) das Acylderivat (II).
Article
Es werden ausführliche NMR-spektroskopische Untersuchungen an Pyrrolizidindiolen beschrieben, die die Zuordnung der Struktur einzelner derartiger Verbindungen gestatten.
Article
Zur Synthese von Macronecin (V) wurde das in Form von (I)⇌(II) vorliegende (±)-1-Carbäthoxy-2,3-dioxo-pyrrolizidin eingesetzt.
Article
N.m.r. measurements show that madurensine has the secondary ester grouping (and bridgehead of the macrocyclic ring) at C-6 rather than at C-7 as previously supposed.
Article
Eighteen pyrrolizidine alkaloids and several derivatives have been examined for tumor-inhibitory properties. Of these, 10 compounds show significant activity against one or more test tumors. Heliotrine, lasiocarpine, monocrotaline, spectabiline, and senecionine are highly active against the Walker 256 (intramuscular) system. The activity pattern is...
Article
Gas—liquid chromatography of pyrrolizidine alkaloids is described. Retention times are tabulated for 58 alkaloids and derivatives and discussed in relation to the molecular structures of the compounds. Minor structural changes are shown to produce additive effects on the logarithm of the relative retention time as has been found with other classes...

Citations

... D. toxica produces several related toxins (Edgar, 1991), the most prominent being phomopsin A ( Culvenor et al., 1977Culvenor et al., , 1989. It has been shown that the level of disease resistance is reflected in the level of phomopsins produced during early stages of latent infection in lupin stems (Williamson et al., 1995). ...
... In fact, the immunized rats showed increased susceptibility to gossypol toxicity. Increased susceptibility to toxicity has also been observed with pyrrolizidine alkaloid senecionine conjugat es in rats (Culvenor, 1978 ), the mycotoxin sporidesmin in sheep (Fairclough et al., 1984 ) and the mycotoxin zearalenone in pigs (MacDougald et al., 1990 ). ...
... The chemical structure of this mycotoxin was determined by physicochemical methods and confirmed by X-ray crystallography (Culvenor et al., 1989;Edgar, 1991). Phomopsin A (Figure 1) is the most commonly reported mycotoxin detected in extracts of field lupins naturally infected with D. toxica and in extracts of in vitro cultures of this fungus (Culvenor et al., 1977(Culvenor et al., , 1978Lanigan et al., 1979;Culvenor et al., 1983;Edgar and Culvenor, 1985;Culvenor et al., 1989;Edgar, 1991). Phomopsin A is normally accompanied by smaller quantities of its de-chloro analogue phomopsin B (Figure 1), which also exhibits toxicity in experimental animals characteristic of lupinosis. ...
... The sequence of the amino acids was established by fast atom bombardment (FAB) mass spectrometry of phomopsin A and its derivatives Edgar 1991) and by heteronuclear 13 C{ 1 H} selective population inversion experiments (Culvenor et al., 1983;Edgar et al., 1986;Culvenor et al., 1989;Edgar, 1991). An X-ray crystallographic study of phomopsin A confirmed the amino acid sequence and showed that the linear hexapeptide is modified by an ether bridge in place of the 5hydroxy group of the N-methyl 3(3-chloro-4,5-dihydroxyphenyl)serine and the hydroxy group of the 3-hydroxyisoleucine units (Mackay et al., 1986;Culvenor et al., 1989). ...
... The synthesis of natural pirrolizidines has been achieved by at least four different routes by Buchanan [53], Bennett [54] and Hudlicky [55] Compound 179 after a few steps as referred in literature afforded crotonecine (178) [56,78,79] (Scheme 31). Alcohol 179b was subjected to deoxygenation by formation of a thiocarbonylimidazolide followed by reduction with tri-n-butylstannane [80] to yield the lactone 185 in 85% overall yield from 184. ...
... stenosiphon [92] Echium tuberculatum [60] Echium vulgare [11,96] Echium wildpretti [99] Onosma stellulatum [60,167] Symphytum aintabicum [170] Symphytum asperum [171] Symphytum bohemium [173] Symphytum caucasium [174] Symphytum consolidum [175] Symphytum sylvaticum [170] Symphytum tuberosum [162] Echimidine isomer (tigloyl) Echium amoenum [87] Echium horridum [90] Cynoglossum furcatum (C. zeylanicum) [74,75] Cynoglossum germanicum [77] Cynoglossum macrostylum [80] Cynoglossum montanum [81] Cynoglossum nervosum [82] Cynoglossum officinale [67,84] Cynoglossum pictum [85] Heliotropium circinatum [114] Heliotropium indicum [130] Heliotropium suaveolens [29] Heliotropium supinum [27,143] Lappula glochidiata [146] Lindelofia longiflora [149] Lindelofia spectabilis [124] Lindelofia stylosa [135] Moltikiopsis ciliata [108] Paracaryum regulosum [40] Paracynoglossum imeretium [29] Rindera austroechinata [57,152] Rindera baldschuanica [152] Rindera cyclodonata [120] Rindera echinata [120] Rindera oblogifolia [152] Rindera umbellata [169] Solenanthus circinnatus [151] Solenanthus coronatus [135] Solenanthus karateginus [151] Symphytum asperum [172] Symphytum caucasium [174] Symphytum officinale [179] Tournefortia sogdiana [57] Echiumine Amsinckia carinata [42] Amsinckia eastwoodiae [42] Amsinckia hispida [44] Amsinckia intermedia [44] [145] Europine Heliotropium arbainense [71] Heliotropium bacciferum [108,109] Heliotropium bovi [110] Heliotropium circinatum [114] Heliotropium crassifolium [115] Heliotropium digynum (H.luteum) [121] Heliotropium dissitiflorum [123] Heliotropium esfandiarii [125] Heliotropium europaeum [126,127,186] Heliotropium hirsutissinum [129] Heliotropium marifolium [29] Heliotropium maris mortui [71] Heliotropium rotundifolium [ [85] Cynoglossium viridiforum [86] Heliotropium supinum [27,143] Myosotis sylvatica [25] Paracaryum regulosum [90] Paracynoglossum imeretium [29] Rindera umbellata [169] Symphytum asperum [171] Symphytum officinale [179] Heliotridine Anchusa milleri [90] Onosma heterophyllum [165] Heliotridine 2S-hydroxy-2S(1S-hydroxyethyl0-4- methyl-pentanoyl ester Anchusa strigosa [50] Heliotrine Arenbia decumbens [52] Cynoglossum nervosum [82] Heliotropium acutifolium [105] H. arbainense [71] H. bacciferum [108,109] Heliotropium circinatum [114] Heliotropium dasycarpum [120] Heliotropium digynum [121] Heliotropium disciforme [122] Heliotropium dissitiflorum [123] Heliotropium eichwaldii [124] Heliotropium europaeum [127,185,186] Heliotropium hirsutissimum [129] Heliotropium indicum [130,131] Heliotropium lasiocarpum [29] [107] Heliotropium indicum [130,131] Heliotropium marifolium [29] Heliotropium transalpinum [144] Messerschmidia argentea [158] Indicinine Heliotropium indicum [130,131] Isoechinatine Cynoglossum furcatum (C. zeylanicum) [75] Isolycopsamine Heliotropium keralense [190] Isoretronocanol (or its isomer) Omphalodes verna [27] 9-(3'-Isovaleryl)viridiflory retronecine Heliotropium curassavicum var. ...
... These pyrrole compounds generate stabilised carbonium ions by the loss of hydroxyl groups that react rapidly with nucleophilic mercapto, hydroxyl and amino groups on proteins and the amino groups of purine and pyrimidine bases in nucleosides like DNA and RNA. In addition, the hydrolysis of didehydropyrrolizidine alkaloids results in pyrrole compounds with alkylating activity towards DNA, proteins and cysteine residues (Culvenor et al., 1969Culvenor et al., , 1971). Based on these reports, it is not surprising that pyrrole compounds can damage proteins, RNA and DNA, resulting in protein synthesis impairment, cellular function loss, tumour development and an anti-mitotic effect. ...
... These PAs are hydrolyzed in the larvae and the resulting necine bases are re-esterified with necic acids of insect origin. Arctiid-specific retronecine esters were frequently observed, i.e. callimorphine (Edgar et al. 1980;Ehmke et al. 1990) and creatonotine Schulz et al. 1993). These compounds represent two classes of arctiid-specific PAs, the callimorphines and the creatonotines (Fig 10.6 I; Hartmann et al. 2005a, b;Beuerle et al. 2007). ...
... All parts of the plant contain, mucronatinine (51), nilgirine (52), usaramine (55), crotastriatine (56), monocrotaline (74), and cromadurine (75). (Chu et al. 1964; Sawhney et al. 1967; Bhacca et al. 1968; Atal et al. 1968; Han et al. 1981; Williams et al. 1987). The plant should not be used medicinically. ...
... More than 400 pyrrolizidine alkaloids (PAs) from over 6000 floriferous plants are widely distributed throughout the world, mainly occurring in the families Compositae , Leguminosae, Orchidaceae and Boraginaceae (Logie et al., 1994; Stegelmeier et al., 1999; Tan et al., 2003 Tan et al., , 2004). PAs with a saturated necine moiety are not normally hepatotoxic (Culvenor et al., 1985), unlike the esters of unsaturated necine (7-hydroxy-1- hydroxymethyl-6,7-dihydro-5H-pyrrolizidine). Hepatotoxic pyrrolizidine alkaloids (HPAs) have been shown to be hepatotoxic (Huxtable, 1989; Prakash et al., 1999; Ji et al., 2002 Ji et al., , 2005 Wang et al., 2006 ), pheumotoxic (Huxtable, 1990; Taylor et al., 1997), genotoxic (Roeder et al., 1984) and neurotoxic (Röeder, 2000). ...