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1

Zhu-Jin, Liu, C. T. Liu, Lu Ren-Rong, and Xu Feng. "A novel approach to the synthesis of 2-benzyl substituted pyrrolizidine and pyrrolizidinone ring systems." Acta Chimica Sinica 6, no. 2 (May 1988): 123–31. http://dx.doi.org/10.1002/cjoc.19880060206.

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2

Dietrich, Evelyne, and William D. Lubell. "Efficient Synthesis of Enantiopure Pyrrolizidinone Amino Acid." Journal of Organic Chemistry 68, no. 18 (September 2003): 6988–96. http://dx.doi.org/10.1021/jo034739d.

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3

Cordero, Franca M., Federica Pisaneschi, Karina Meschini Batista, Silvia Valenza, Fabrizio Machetti, and Alberto Brandi. "A New Bicyclic Dipeptide Isostere with Pyrrolizidinone Skeleton." Journal of Organic Chemistry 70, no. 3 (February 2005): 856–67. http://dx.doi.org/10.1021/jo0487653.

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4

SUGIE, YUTAKA, HIDEO HIRAI, HIROKO KACHI-TONAI, YOON-JEONG KIM, YASUHIRO KOJIMA, YUKIO SHIOMI, AKEMI SUGIURA, et al. "New Pyrrolizidinone Antibiotics CJ-16,264 and CJ-16,367." Journal of Antibiotics 54, no. 11 (2001): 917–25. http://dx.doi.org/10.7164/antibiotics.54.917.

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5

Escolano, Marcos, Javier Torres Fernández, Fernando Rabasa-Alcañiz, María Sánchez-Roselló, and Carlos del Pozo. "Enantioselective Synthesis of Pyrrolizidinone Scaffolds through Multiple-Relay Catalysis." Organic Letters 22, no. 24 (November 30, 2020): 9433–38. http://dx.doi.org/10.1021/acs.orglett.0c03344.

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6

Nogawa, Toshihiko, Makoto Kawatani, Masakazu Uramoto, Akiko Okano, Harumi Aono, Yushi Futamura, Hiroyuki Koshino, Shunji Takahashi, and Hiroyuki Osada. "Pyrrolizilactone, a new pyrrolizidinone metabolite produced by a fungus." Journal of Antibiotics 66, no. 10 (May 29, 2013): 621–23. http://dx.doi.org/10.1038/ja.2013.55.

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7

Salvati, Maria, Franca M. Cordero, Federica Pisaneschi, Francesca Bucelli, and Alberto Brandi. "New developments in the synthesis of pyrrolizidinone-based dipeptide isosteres." Tetrahedron 61, no. 37 (September 2005): 8836–47. http://dx.doi.org/10.1016/j.tet.2005.07.020.

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8

Sugie, Yutaka, and et al et al. "ChemInform Abstract: New Pyrrolizidinone Antibiotics CJ-16,264 and CJ-16,367." ChemInform 33, no. 21 (May 21, 2010): no. http://dx.doi.org/10.1002/chin.200221182.

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9

Rao, Mallem H. V. Ramana, Eulàlia Pinyol, and William D. Lubell. "Rigid Dipeptide Mimics: Synthesis of Enantiopure C6-Functionalized Pyrrolizidinone Amino Acids." Journal of Organic Chemistry 72, no. 3 (February 2007): 736–43. http://dx.doi.org/10.1021/jo0616761.

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10

Chiacchio, Ugo, Antonino Corsaro, Venerando Pistarà, Antonio Rescifina, Giovanni Romeo, and Roberto Romeo. "An asymmetric approach to pyrrolidinone and pyrrolizidinone systems by intramolecular oxime-olefin cycloaddition." Tetrahedron 52, no. 23 (June 1996): 7875–84. http://dx.doi.org/10.1016/0040-4020(96)00358-4.

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11

Baker, S. Richard, Keith I. Burton, Andrew F. Parsons, Jean-François Pons, and Michelle Wilson. "Tandem radical cyclisation of enamides mediated by tin hydride; pyrrolizidinone or indolizidinone ring formation." Journal of the Chemical Society, Perkin Transactions 1, no. 4 (1999): 427–36. http://dx.doi.org/10.1039/a809282f.

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12

Li, Li, Man-Cheng Tang, Shoubin Tang, Shushan Gao, Sameh Soliman, Leibniz Hang, Wei Xu, Tao Ye, Kenji Watanabe, and Yi Tang. "Genome Mining and Assembly-Line Biosynthesis of the UCS1025A Pyrrolizidinone Family of Fungal Alkaloids." Journal of the American Chemical Society 140, no. 6 (February 2, 2018): 2067–71. http://dx.doi.org/10.1021/jacs.8b00056.

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13

CHIACCHIO, U., A. CORSARO, V. PISTARA, A. RESCIFINA, G. ROMEO, and R. ROMEO. "ChemInform Abstract: An Asymmetric Approach to Pyrrolidinone and Pyrrolizidinone Systems by Intramolecular Oxime-Olefin Cycloaddition." ChemInform 27, no. 39 (August 4, 2010): no. http://dx.doi.org/10.1002/chin.199639142.

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14

Hanessian, Stephen, Ronald Buckle, and Malken Bayrakdarian. "Design and Synthesis of a Novel Class of Constrained Tricyclic Pyrrolizidinone Carboxylic Acids as Carbapenem Mimics." Journal of Organic Chemistry 67, no. 10 (May 2002): 3387–97. http://dx.doi.org/10.1021/jo0111715.

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15

Baker, S. Richard, Keith I. Burton, Andrew F. Parsons, Jean-Francois Pons, and Michelle Wilson. "ChemInform Abstract: Tandem Radical Cyclization of Enamides Mediated by Tin Hydride; Pyrrolizidinone or Indolizidinone Ring Formation." ChemInform 30, no. 28 (June 14, 2010): no. http://dx.doi.org/10.1002/chin.199928051.

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16

Hanessian, Stephen, Ronald Buckle, and Malken Bayrakdarian. "ChemInform Abstract: Design and Synthesis of a Novel Class of Constrained Tricyclic Pyrrolizidinone Carboxylic Acids as Carbapenem Mimics." ChemInform 33, no. 39 (May 19, 2010): no. http://dx.doi.org/10.1002/chin.200239112.

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17

Beabout, Kathryn, Megan D. McCurry, Heer Mehta, Akshay A. Shah, Kiran Kumar Pulukuri, Stephan Rigol, Yanping Wang, K. C. Nicolaou, and Yousif Shamoo. "Experimental Evolution of Diverse Strains as a Method for the Determination of Biochemical Mechanisms of Action for Novel Pyrrolizidinone Antibiotics." ACS Infectious Diseases 3, no. 11 (September 27, 2017): 854–65. http://dx.doi.org/10.1021/acsinfecdis.7b00135.

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18

Griesbeck, Axel G., Harald Mauder, and Ingrid Müller. "Photochemistry ofN-Phthaloyl α-Amino Acid Esters: A New Approach to β,γ-Unsaturated α-Amino Acid, Dihydrobenzazepinedione, and Pyrrolizidinone Derivatives." Chemische Berichte 125, no. 11 (November 1992): 2467–75. http://dx.doi.org/10.1002/cber.19921251119.

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19

GRIESBECK, A. G., H. MAUDER, and I. MUELLER. "ChemInform Abstract: Photochemistry of N-Phthaloyl α-Amino Acid Esters: A New Approach to β,γ-Unsaturated α-Amino Acids, Dihydrobenzazepinediones, and Pyrrolizidinone Derivatives." ChemInform 24, no. 10 (August 20, 2010): no. http://dx.doi.org/10.1002/chin.199310106.

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20

Kopp, Thomas, Liesa Salzer, Mona Abdel-Tawab, and Boris Mizaikoff. "Efficient Extraction of Pyrrolizidine Alkaloids from Plants by Pressurised Liquid Extraction – A Preliminary Study." Planta Medica 86, no. 01 (October 21, 2019): 85–90. http://dx.doi.org/10.1055/a-1023-7419.

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AbstractPyrrolizidine alkaloids and their corresponding pyrrolizidine alkaloid-N-oxides are secondary plant constituents that became the subject of public concern due to their hepatotoxic, pneumotoxic, genotoxic, and cytotoxic effects. In contrast to the well-established analytical separation and detection methods, only a few studies have investigated the extraction of pyrrolizidine alkaloids/pyrrolizidine alkaloid-N-oxides from plant material. In this study, we have applied pressurized liquid extraction with the aim of evaluating the effect of various parameters on the recovery of pyrrolizidine alkaloids. The nature of the modifier (various acids, NH3) added to the aqueous extraction solvent, its concentration (1 or 5%), and the temperature (50 – 125 °C) were systematically varied. To analyse a wide range of structurally different pyrrolizidine alkaloids, Jacobaea vulgaris (syn. Senecio jacobaea), Tussilago farfara, and Symphytum officinale were included. Pyrrolizidine alkaloids were quantified by HPLC-MS/MS and the results obtained by pressurised liquid extraction were compared with the amount of pyrrolizidine alkaloids determined by an official reference method. Using this approach, increased rates of recovery were obtained for J. vulgaris (up to 174.4%), T. farfara (up to 156.5%), and S. officinale (up to 288.7%). Hence, pressurised liquid extraction was found to be a promising strategy for the complete and automated extraction of pyrrolizidine alkaloids, which could advantageously replace other time- and solvent-consuming extraction methods.
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21

Kopp, Thomas, Mona Abdel-Tawab, and Boris Mizaikoff. "Core Imprinting: An Alternative and Economic Approach for Depleting Pyrrolizidine Alkaloids in Herbal Extracts." Planta Medica International Open 7, no. 01 (March 18, 2020): e26-e33. http://dx.doi.org/10.1055/a-1121-4868.

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AbstractDue to the high toxicity of pyrrolizidine alkaloids, in 2011, the German Federal Institute of Risk Assessment recommended that their daily intake limit should be no more than 0.007 µg/kg body weight. The risk of ingesting these substances in herbal preparations, either from their inherent presence in plants or through contamination with pyrrolizidine alkaloid-containing weeds, should not be underestimated. A promising molecular imprinted polymer was developed previously to minimise exposure to these compounds. Due to the high costs of the template and the risk of template bleeding, an alternative and more economic pyrrolizidine alkaloid depleting strategy is still required. Core imprinting, which focuses on the most important structural element in the target molecule, was investigated using triethylamine and tetraethylammonium as easily available and cheap alternative templates. The suitability of core imprinting was demonstrated using a pyrrolizidine alkaloid standard solution if an excess of an alternative template compared to monocrotaline was used for imprinting. Matrix trials in pyrrolizidine alkaloid-spiked Mentha piperita, Chelidonium majus, Glycyrrhiza glabra, and Matricaria chamomilla extracts containing Echium vulgare revealed better pyrrolizidine alkaloid binding than demonstrated for the original molecular imprinted polymer. Echimidine and echimidine-N-oxide were depleted in the range of 31.8–70.0 and 26.1–45.1%, respectively. However, solvent-dependent differences in pyrrolizidine alkaloid binding and inherent plant analytical marker compounds were observed. Hence, binding of analytical marker compounds was better minimised in methanolic than in ethanolic extracts. The present study reveals core imprinting to be an economic alternative approach for depleting pyrrolizidine alkaloids in plant extracts.
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22

Kopp, Thomas, Mona Abdel-Tawab, Martin Khoeiklang, and Boris Mizaikoff. "Development of a Selective Adsorbing Material for Binding of Pyrrolizidine Alkaloids in Herbal Extracts, Based on Molecular Group Imprinting." Planta Medica 85, no. 13 (August 5, 2019): 1107–13. http://dx.doi.org/10.1055/a-0961-2658.

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AbstractPyrrolizidine alkaloids are secondary plant constituents that became a subject of public concern because of their hepatotoxic, pneumotoxic, genotoxic, and cytotoxic effects. Due to disregardful harvesting and/or contamination with pyrrolizidine alkaloid-containing plants, there is a high risk of ingesting these substances with plant extracts or natural products. The limit for the daily intake was set to 0.007 µg/kg body weight. If contained in an extract, cleanup methods may help to minimize the pyrrolizidine alkaloid concentration. For this purpose, a material for depleting pyrrolizidine alkaloids in herbal preparations was developed based on the approach of molecular imprinting using monocrotaline. Molecular imprinted polymers are substances with specific binding characteristics, depending on the template used for imprinting. By means of group imprinting, only one molecule is used for creating selective cavities for many molecular pyrrolizidine alkaloid variations. Design of Experiment was used for the development using a 25 screening plan resulting in 64 polymers (32 MIPs/32 NIPs). Rebinding trials revealed that the developed material can compete with common cation exchangers and is more suitable for depleting pyrrolizidine alkaloids than C18- material. Matrix trials using an extract from Chelidonium majus show that there is sufficient binding capacity for pyrrolizidine alkaloids (80%), but the material is lacking in selectivity towards pyrrolizidine alkaloids in the presence of other alkaloids with similar functional groups such as berberine, chelidonine, and coptisine. Beyond this interaction, the selectivity could be proven for other structurally different compounds on the example of chelidonic acid.
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23

Nickisch-Rosenegk, Eva von, Dietrich Schneider, and Michael Wink. "Time-Course of Pyrrolizidine Alkaloid Processing in the Alkaloid Exploiting Arctiid Moth, Creatonotos transiens." Zeitschrift für Naturforschung C 45, no. 7-8 (August 1, 1990): 881–94. http://dx.doi.org/10.1515/znc-1990-7-822.

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Abstract The processing of dietary pyrrolizidine alkaloids by larvae and adults of the arctiid moth Creatonotos transiens was studied in time-course experiments: In larvae, pyrrolizidine alkaloid uptake is quickly followed by the transformation of the alkaloids into their N-oxides. Further- more, if 7 S-heliotrine is applied, a stereochemical inversion of the hydroxyl group at C 7 to 7 R-heliotrine can be observed within 48 h of feeding. The rate of this biotransformation is substantially higher in males which use the 7 R-form later as a precursor for the biosynthesis of 7 R-hydroxydanaidal, a pheromone. The resorbed pyrrolizidine alkaloids are deposited in the integument within 48 h, where they remain stored during the larval, pupal and partly also the imaginal stages. Virtually no alkaloids are lost during ecdysis. Some pyrrolizidine alkaloids can be recovered from the meconium which is released at eclosion by the imagines especially when disturbed. In the adults pyrrolizidine alkaloids are processed in different ways by the two sexes: In females, about 50-80% of total alkaloids are transferred from the integument to the ovaries and the eggs within 2 - 3 days after eclosion. If females mate with alkaloid-rich males they additionally receive with the spermatophore up to 290 jig pyrrolizidine alkaloid, which are further translocated to the eggs. A biparental endowment of eggs with acquired defence alkaloids is thus achieved. In males, 30-50% of pyrrolizidine alkaloids remain in the integu- ment; about 10 - 30% are transferred to the scent organ, the corema, where they are converted into 7 R-hydroxydanaidal. Another part (about 40%) is passed to the spermatophore. In the laboratory experiments, the sizes of the coremata and their respective 7 R-hydroxydanaidal contents are strongly dependent on the availability of dietary pyrrolizidine alkaloids during L6 and especially L7 stages. In the L7 stage even short-term feeding (4-6 h) on Senecio jaco- haea is sufficient to induce large coremata.
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24

Singh, Bharat, and Ram A. Sharma. "Pyrrolizidine Alkaloids and their Biological Properties from Indian Heliotropium Species." Current Bioactive Compounds 15, no. 1 (February 6, 2019): 3–18. http://dx.doi.org/10.2174/1573407213666171120163307.

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Background: Pyrrolizidine alkaloids (PAs) are a group of plant secondary metabolites which protect the plants from biotic stresses by stimulating defense mechanisms as well as adaptability. The pyrrolizidine alkaloids widely occur in members of Boraginaceae family. This review paper describes about the structural properties of various PAs isolated from various Indian Heliotropium species and their biological and pharmacological activities. Methods: Authors surveyed the per-reviewed research, review papers and bibliographic databases and incorporated in this review paper. We have focused our attention on the answers of reviewed questions. The main themes and characteristics of reviewed papers have been described in this review paper. Results: Twenty three species of Heliotropium genus were reviewed critically and have included in this review paper. The review paper contains the critical information of ethnomedicinal properties of each species of Heliotropium genus, the occurrence of pyrrolizidine alkaloids, the biological and pharmacological properties of pyrrplizidine alkaloids. So many pyrrolizidine alkaloids and their N-oxides possess anticancer activity. Some PAs have demonstrated cytotoxic effects also. Conclusion: The findings of this review paper validate the significance of pyrrolizidine alkaloids, their occurrence and biosynthesis in Heliotropium species, as well as their biological and pharmacological properties.
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25

Wu, Mingshu, Jie Jiang, Zhongxiang Zhu, and Dulin Kong. "Catalyst-Free Intramolecular 1,3-Dipolar Cycloaddition of Ethyl (2-Formylphenyl) Vinylphosphonates: A Highly Stereoselective Access to Phosphadihydrocoumarin-Fused Pyrrolizidines/Pyrrolidines." Synthesis 49, no. 16 (May 8, 2017): 3731–39. http://dx.doi.org/10.1055/s-0036-1588818.

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Pyrrolizidine and coumarins both have biological activities, and their molecular skeletons are commonly found in several biomolecules and drug molecules. We have developed a catalyst-free, intramolecular 1,3-dipolar cycloaddition to synthesize phosphadihydrocoumarin-fused pyrrolizidine/pyrrolidine scaffolds with high stereoselectivity.
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26

Mandic, Boris, Dejan Godjevac, Vladimir Beskoski, Milena Simic, Snezana Trifunovic, Vele Tesevic, Vlatka Vajs, and Slobodan Milosavljevic. "Pyrrolizidine alkaloids from seven wild-growing Senecio species in Serbia and Montenegro." Journal of the Serbian Chemical Society 74, no. 1 (2009): 27–34. http://dx.doi.org/10.2298/jsc0901027m.

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The genus Senecio (family Asteraceae) is one of the largest in the world. It comprises about 1100 species which are the rich source of pyrrolizidine alkaloids. Plants containing pyrrolizidine alkaloids are among the most important sources of human and animal exposure to plant toxins and carcinogens. The pyrrolizidine alkaloids of seven Senecio species (S. erucifolius, S. othonnae, S. wagneri, S. subalpinus, S. carpathicus, S. paludosus and S. rupestris) were studied. Fourteen alkaloids were isolated and their structures determined from spectroscopic data (1H- and 13C-NMR, IR and MS). Five of them were identified in S. erucifolius, four in S. othonnae, two in S. wagneri, four in S. subalpinus, two in S. carpathicus, three in S. paludosus and three in S. rupestris. Seven pyrrolizidine alkaloids were found for the first time in particular species. The results have chemotaxonomic importance. The cytotoxic activity and antimicrobial activity of some alkaloids were also studied.
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27

Anderton, N., JJ Gosper, and C. May. "The Inclusion of Pyrrolizidine Alkaloids by α- and β-Cyclodextrins." Australian Journal of Chemistry 47, no. 5 (1994): 853. http://dx.doi.org/10.1071/ch9940853.

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The association constants of α- and β- cyclodextrins with several pyrrolizidine alkaloids have been determined at pH 1.5 and 9.2 by using competitive spectrophotometry and solubility studies, respectively. Evidence of the nature of the pyrrolizidine alkaloids inclusion within the cyclodextrin cavity is presented.
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28

Boppre, Michael, and Brian R. Pitkin. "Attraction of Chloropid Flies to Pyrrolizidine Alkaloids (Diptera: Chloropidae)." Entomologia Generalis 13, no. 1-2 (May 1, 1988): 81–85. http://dx.doi.org/10.1127/entom.gen/13/1988/81.

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29

Zhao, Xiang-Lan, Mo-Yin Chan, and C. W. Ogle. "The Identification of Pyrrolizidine Alkaloid-Containing Plants - A Study on 20 Herbs of the Compositae Family." American Journal of Chinese Medicine 17, no. 01n02 (January 1989): 71–78. http://dx.doi.org/10.1142/s0192415x89000127.

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Twenty Chinese medicinal herbs of the Compositae family were investigated for the presence of pyrrolizidine alkaloid. Of these, only the Eupatorium species were shown to contain pyrrolizidine alkaloid. The amount present was found to vary with species, parts of the plant used, purchase sources and extraction methods. Possible toxicity from the use of these herbs is discussed.
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30

&NA;. "Pyrrolizidine alkaloids." Reactions Weekly &NA;, no. 1254 (May 2009): 36. http://dx.doi.org/10.2165/00128415-200912540-00109.

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31

&NA;. "Pyrrolizidine alkaloids." Reactions Weekly &NA;, no. 1255 (June 2009): 28. http://dx.doi.org/10.2165/00128415-200912550-00081.

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32

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 7, no. 5 (1990): 377. http://dx.doi.org/10.1039/np9900700377.

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33

Richard Liddell, James. "Pyrrolizidine alkaloids." Natural Product Reports 15, no. 4 (1998): 363. http://dx.doi.org/10.1039/a815363y.

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34

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 10, no. 5 (1993): 487. http://dx.doi.org/10.1039/np9931000487.

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35

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 8, no. 3 (1991): 213. http://dx.doi.org/10.1039/np9910800213.

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36

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 9, no. 4 (1992): 313. http://dx.doi.org/10.1039/np9920900313.

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37

Liddell, J. Richard. "Pyrrolizidine alkaloids." Natural Product Reports 14, no. 6 (1997): 653. http://dx.doi.org/10.1039/np9971400653.

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38

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 11, no. 6 (1994): 613. http://dx.doi.org/10.1039/np9941100613.

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39

Liddell, J. Richard. "Pyrrolizidine alkaloids." Natural Product Reports 13, no. 3 (1996): 187. http://dx.doi.org/10.1039/np9961300187.

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40

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 12, no. 4 (1995): 413. http://dx.doi.org/10.1039/np9951200413.

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41

Robertson, Jeremy, and Kiri Stevens. "Pyrrolizidine alkaloids." Nat. Prod. Rep. 31, no. 12 (2014): 1721–88. http://dx.doi.org/10.1039/c4np00055b.

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42

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 2, no. 3 (1985): 213. http://dx.doi.org/10.1039/np9850200213.

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43

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 3 (1986): 297. http://dx.doi.org/10.1039/np9860300297.

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44

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 4 (1987): 577. http://dx.doi.org/10.1039/np9870400577.

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45

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 6, no. 3 (1989): 221. http://dx.doi.org/10.1039/np9890600221.

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46

Robins, D. J. "Pyrrolizidine alkaloids." Natural Product Reports 6, no. 6 (1989): 577. http://dx.doi.org/10.1039/np9890600577.

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47

Liddell, James R., James R. Liddell, and James R. Liddell. "Pyrrolizidine alkaloids." Natural Product Reports 16, no. 4 (1999): 499–507. http://dx.doi.org/10.1039/a802501k.

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48

Liddell, James R. "Pyrrolizidine alkaloids." Natural Product Reports 19, no. 6 (September 17, 2002): 773–81. http://dx.doi.org/10.1039/b108975g.

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49

Huxtable, Ryan J., and Dennis V. C. Awang. "Pyrrolizidine poisoning." American Journal of Medicine 89, no. 4 (October 1990): 547–48. http://dx.doi.org/10.1016/0002-9343(90)90403-z.

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50

Edgar, J. A., H. J. Lin, C. R. Kumana, and M. M. T. Ng. "Pyrrolizidine Alkaloid Composition of Three Chinese Medicinal Herbs, Eupatorium cannabinum, E. japonicum and Crotalaria assamica." American Journal of Chinese Medicine 20, no. 03n04 (January 1992): 281–88. http://dx.doi.org/10.1142/s0192415x92000291.

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The pyrrolizidine alkaloid composition of three Chinese herbs, "pei lan", "cheng gan cao" and "zi xiao rong" identified respectively as Eupatorium cannabinum, Eupatorium japonicum (Compositae) and Crotalaria assamica (Leguminosae), were studied by fast atom bombardment mass spectrometry and gas chromatography-electron impact mass spectrometry. Viridiflorine, cynaustraline, amabiline, supinine, echinatine, rinderine and isomers of these alkaloids were found in the Eupatorium species. Monocrotaline was the only pyrrolizidine alkaloid detected in the Crotalaria species.
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