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Open AccessReview

Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties

1
Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University, Zagazig 44519, Egypt
2
Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany
*
Author to whom correspondence should be addressed.
Diversity 2014, 6(2), 188-282; https://doi.org/10.3390/d6020188
Received: 6 February 2014 / Revised: 24 February 2014 / Accepted: 13 March 2014 / Published: 1 April 2014

Abstract

Among the diversity of secondary metabolites which are produced by plants as means of defence against herbivores and microbes, pyrrolizidine alkaloids (PAs) are common in Boraginaceae, Asteraceae and some other plant families. Pyrrolizidine alkaloids are infamous as toxic compounds which can alkylate DNA und thus cause mutations and even cancer in herbivores and humans. Almost all genera of the family Boraginaceae synthesize and store this type of alkaloids. This review reports the available information on the present status (literature up to early 2014) of the pyrrolizidine alkaloids in the Boraginaceae and summarizes the topics structure, distribution, chemistry, chemotaxonomic significance, and biological properties.
Keywords: pyrrolizidine alkaloids; Boraginaceae; distribution; structures; NMR spectroscopy; mass spectrometry; biological properties pyrrolizidine alkaloids; Boraginaceae; distribution; structures; NMR spectroscopy; mass spectrometry; biological properties

1. Introduction

Pyrrolizidine alkaloids (PAs) are common secondary metabolites in Boraginaceae, Fabaceae (tribe Crotalarieae) and Asteraceae (tribe Senecioneae) and serve as chemical defence compounds mainly against herbivores [1,2]. Several PA producing plants grow as weeds and therefore occur widely in agricultural production system throughout the world. They can enter the human food chain as a result of co-harvesting PA containing plants with edible grains. When bees visit areas, in which PA plants are abundant, PAs can be transferred into honey because nectar and pollen of PA plants contain alkaloids [3]. PA-contaminated human food can include cereals, milk, honey, eggs, and meat. In addition a PA-intake can occur when herbal teas and traditional medicines of the PA-containing plants are consumed [4,5,6,7,8,9,10,11,12,13,14,15,16,17].
Chronic health problems have been attributed to the presence of PAs in these products. The long-term toxicity is due to the conversion of pyrrolizidine alkaloids to the corresponding pyrrole derivatives which are highly reactive; they can alkylate DNA and have the ability to form DNA cross-linkage. As a consequence DNA replication is interrupted and mutations can occur, which can lead to liver and kidney cancer [6,18,19]. The ring nucleus (necine base) with a double bond in the 1:2 position is essential for genotoxic effects of theses alkaloids. PAs are bitter and modulate several neuroreceptors, including 5-HT receptors [20,21,22] which can induce immediate food avoidance in herbivores.
Many of the PAs have been shown to exhibit hepatotoxic, pulmotoxic, haemolytic, antimitotic, teratogenic, mutagenic and carcinogenic effects [22,23,24,25,26,27,28,29,30,31,32,33,34,35,36].
Plants of the family Boraginaceae are famous for the production of PAs. These alkaloids occur as free necines (either the necine base heliotridine or retronecine) or as a mixture of free bases and their N-oxides. They can form single esters (monoester) at C-9 or C-7, open chain diesters at both C-7 and C-9 of the necine base, or in rare cases macrocyclic diesters linking C-7 with C-9 (Figure 1 and Figure 2).
Several reviews on the occurrence of PAs have been published already [23,24,25,26,27,28,29,30,31,32,35,37,38,39] In the present review, we have made a complete review of PAs in Boraginaceae and have added also older records which were not covered so far. Table 1 and Table 2 list the distribution of PAs in the Boraginaceae (a last comprehensive review was published by Hartmann and Witte [29]). GLC and GLC-MS data are tabulated in Table 3. For NMR data, we have only included NMR data of new PAs from the Boraginaceae in the time frame 1991–2013 for 13C (Table 4) and 1994–2013 for 1H (Table 5).
Figure 1. Basic structures of pyrrolizidine alkaloids in Boraginaceae.
Figure 1. Basic structures of pyrrolizidine alkaloids in Boraginaceae.
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Figure 2. Necic acids occurring in pyrrolizidine alkaloids of Boraginaceae.
Figure 2. Necic acids occurring in pyrrolizidine alkaloids of Boraginaceae.
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Table 1. List of plant species of the Boraginaceae containing PAs.
Table 1. List of plant species of the Boraginaceae containing PAs.
SpeciesPyrrolizidine alkaloidsReferences
Alkanna orientalis7-Angeloylretronecine, 9-angeloylretronecine, 7-tigloylretronecine, 9-tigloylretronecine, 7-seneioylretronecine, 9-senecioylretronecine, triangularine, dihydroxytriangularine, triangularicine, dihydroxytriangularicine, 7-angeloyl-9-(hydroxypropenoyl) retronecine, 7-tigloyl-9-(hydroxypropenoyl) retronecine, 7-angeloyl-9-(2,3-dihydroxypropanoyl) retronecine, 7-tigloyl-9-(2,3-dihydroxypropanoyl) retronecine.[40,41]
A. tinctoria (A. tuberculata)7-Angeloylretronecine, 7-tigloylretronecine, 9-tigloylretronecine, triangularine, dihydroxytriangularine, triangularicine, dihydroxytriangularicine, 7-acetyl-9-sarracinoylretronecine, 7-angeloyl-9-(hydroxypropenoyl) retronecine, 7-tigloyl-9-(hydroxypropenoyl) retronecine, 7-angeloyl-9-(2,3-dihydroxypropanoyl) retronecine, 7-tigloyl-9-(2,3-dihydroxypropanoyl) retronecine.[40,41]
Amsinckia carinataEchiumine, furcatine, 3'-acetylfurcatine, intermedine, 7-acetylintermedine, lycopsamine, myoscorpine, supinine.[42]
A. douglasianaAmabiline, cynaustrline, intermedine, lycopsamine, tessellatine, 9-(3'-acetylviridifloryl)turniforcidine.[42,43]
A. eastwoodiaeAmabiline, intermedine, 3'-acetylintermedine, echiumine, lindelofine, lycopsamine, supinine, tessellatine.[42]
A. furacataFurcatine, intermedine, 3'-acetylfurcatine, lycopsamine, supinine, tessellatine.[42]
A. grandifloraAmabiline, intermedine, lycopsamine, 3'-aetyllycopsamine, 7-acetyllycopsamine, tessellatine, 9-acetyltessellatine.[42]
A. hispidaEchiumine, intermedine, lycopsamine.[44]
A. intermediaEchiumine, intermedine, lycopsamine, sincamidine.[44]
A. lunarisLycopsamine, 3'-acetyllycopamine, intermedine, supinine, tesslatine, 9'-acetyltessellatine.[42]
A. lycopsoidesAmabiline, echiumine, intermedine, 3'-acetylintermedine, lycopsamine, supinine, tessellatine.[42,44]
A. lycopsoides × menziesii var. intermediaAmabiline, intermedine, 3'-acetylintermedine, lycopsamine, supinine, tessellatine.[42]
A. menziesiiIntermedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine, 3',7-diacetyllycopsamine.[45]
A. menziesii var. intermediaAmabiline, cynaustraine (or steroisomer), echiumine, 3'-acetylechiumine, intermedine, 3'-acetylintermedine, 7-acetylintermedine, 3',7-diacetylintermedine, lindelfoline, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine, myscorpine, 3'-acetylmyscorpine, supinine, symlandine, tessellatine.[42,43]
A. retrosaAmabiline, intermedine, 3'-acetylintermedine, lycopsamine, myscorpine, 3'-acetylmyscorpine, supinine, tessellatine.[42]
A. spectabilis var. microcarpaIntermedine, 3'-acetylintermedine, lindelofine, lycopsamine, myscorpine, supinine, tessellatine.[42]
A. specabtilis var. spectabilisIntermedine, 3'-actylintermedine, lindelofine, lycopsamine, supinine.[42]
A. spectabilis var. nicolaiIntermedine, lindelofine, lycopsamine, tessellatine, trachelanthamine, supinine.[42]
A. tessellataIntermedine, lycopsamine, 3'-acetylintermedine, 3'-acetyllycopsamine, 7-acetylintermedine, 7-acetyllycopsamine, 3',7-diacetylintermedine, 3'-7-diacetyllycopsamine.[46]
A. tessellata var. gloriosaAmabiline, intermedine, lycopsamine, supinine, tessellatine, tracelanthamine, viridiflorine, 3'-acetylviridiflorine.[42,43]
A. tessellata var. tessellataAmabiline, intermedine, lycopsamine, 3'-acetyllycopsamine, tessellatine, 3'-acetyltessellatine, 9-acetyltessellatine, 9,3'-acetyltessellatine, 9-(3'-acetylviridifloryl)-turniforcidine.[42]
A. vernicosaFurcatine, intermedine, lycopsamine, supinine, 7-trachelanthyl retronecine.[42]
Anchusa arvensis (=Lycopsis arvensis)Echinatine, intermedine, 7-acetylintermedine, lycopsamine, 7-acetyllycopsamine, 3',7-diacetylintermedine (or its isomer 3',7-diaetyllycopsamine), supinine, 9-acetyltrachelanthamidine, 9-angeloyltrachelanthamidine.[40,47]
A. hispida (=Gastrocotyle hispida)7-Angeloylheliotridine, intermedine, lyopsamine, 7-acetyllycopsamine, retronecine, trachelanthamine and its isomer.[40]
A. milleriHeliotridine, 7-angeloylheliotridine, rinderine, retronecine, supinine, viridiflorine, 9-curassavoyleliotridine, 7-acetyl-9-curassavoylheliotridine.[40]
A. officinalisIntermedine, curassavine, lycopsamine, 7-aceyllycopsamine.[47,48,49]
A. strigosaHeliotridine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester, platyneine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester, retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester and its N-oxide, retronecine 2S-hydroxy-2S(1R-hydroxyethyl)-4-methyl-pentanoyl ester and its N-oxide, retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-[1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester, supinidine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester, trachelanthamidine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester.[50,51]
Arnebia decumbens7-angeloylrtronecine, 9-angeloylretronecine, 7-tigloylrtronecine, 9-tigloylretronecine, europine, heliotrine, lycopsamine, rinderine, supinine.[52]
Arnebia euchroma7-angeloylrtronecine, 9-angeloylretronecine[53]
A. hispidissimaEchimidine, monocrotaline.[54]
Asperugo procumbensAmabiline (or supinine), echinatine.[47]
Borago officinalisAmabiline, intermedine, 7-acetylintermedine, lycopsamine, 7-acetyllycopsamine, supinine, thesinine, thesinine-4'- O-β-D-glucoside.[55,56]
Caccinia crassifoliaSupinine, Heliotridine or retronecine trachelanthate.[57]
C. glaucaRetronecine 7:9 -dibenzoate.[58]
Cerinthe glabraLycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine, 3',7-diacetyllycopsamine, supinine, 7-hydroxymethyl butyryl-9-viridifloryl-retronecine (or isomer).[59]
Cerinthe minorIntermedine, 7-angeloylretronecine, 9-angeloyl-7-viridiflorylretronecine, lycopsamine.[60,61]
Cordia myxamacrophylline[62]
C. sinensisfloridanine[62]
Cryptantha canaIntermdine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine.[63]
C. clevelandiiIntermdine, 3'-acetylintermedine, echiumine, 2'',3''-epoxyechiumine, thero-2',3' dihydroxyechiumine, erytho-3''-chloro-2''-hydroxyechiumine.[63]
C. confertifloraAmabiline, intermedine, lycopsamine, tessellatine, 9-acetyltessellatine.[63]
C. crassipesLycopsamine, intermedine and their 3'-acetyllycopsamine, 3'-acetylintermedine, 7-acetyllycopsamine, 7-acetylintermedine, amabiline, echiumine, dihydroechumine, echimiplatine, lepanthine.[64]
C. fendleri7-Angeloylretronecine, 9-angeloylretronecine, latifoline, neolatifoline.[63]
C. flavaIntermedine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine.[63]
C. inequataEchimidine, acetylechimidine, echiuplatine, methylechiuplatine, lycopsamine, intermedine, dihydroxyechiumine.[65]
C. jamesiiIntermedine, lycopsamine, 3'- acetyllycopsamine, 7-aetyllyopsamine.[66]
C. leiocarpa7-Angeloylretronecine, 9-angeloylretronecine, echiumine, intermedine, 3'-acetylintermedine, 2'',3''-epoxyechiumine, thero-2',3'-dihydroxyechiumine, erytho-3''-chloro-2''-hydroxyechiumine[63]
C. thyrsifloraIntermedine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine[63]
C. utahensisCryptanthine[65]
C. virgataIntermedine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine[63]
C. virginiensisAmabiline, intermedine, lycopsamine, tessellatine.[63]
Cynoglossum amabileAmabiline, echinatine, 7-acetylechinatine, lycopsamine, rinderine, supinine. 9-angeloylretronecine, 9-angeloyl-7-viridiflorylretronecine,[60,67,68]
C. australeCynausine, cynaustraline.[68]
C. clandestinum9-Angeloyl-7-viridiflorylretronecine, trachelanhamine[60]
C. columnaeN-oxides of echintine, rinderine, 3’-acetylrinderine, 7-tigloyl-9-(2-deoxy-2-methyl)echimidinyl heliotridine.[69]
C. creticumCynoglossamine, echinatine, 3'-acetylechinatine, heliosupine, 3'-acetylheliosupine, 7-angeloylheliotridine, 7-angeloyl-9-(methylbutyryl) heliotridine, 7α-angeloyl-1-chloromethyl-1,2-dehydropyrrolizidine, 7-senecioylheliotridine, rinderine, 3'-acetylrenderine, supinine, trachelanthamine (or isomer).[70,71,72]
C. furcatum (C. zeylanicum)Echinatine, isoechinatine, neocoromandaline, cynaustraline, lactodine, viridinatine[73,74,75,76]
C. germanicumEchinatine, viridiflorine.[77]
C. glochidiatumAmabiline[78]
C. lanceolatumCynaustine, cynaustraline.[78]
C. latifolium7-Angeloylheliotridine, latifoline.[79]
C. macrostylumEchinatine, heliosupine.[80]
C. montanumCynaustine, cynaustraline, echinatine, heliosupine.[81]
C. nervosumHeliotrine, echinatine, rinderine and their N-oxides.[82]
C. officinaleEchinatine, 3'-acetylechinatine, 7-angeloylechinatine, heliosupine, 3'-acetylheliosupine, 7-angeloylheliotridine, 7-angeloyl-1-formyl-6,7-dihydro-5H-pyrrolizidine, 7-angeloyl-9-(2-methylbutyryl)heliotridine, 7-angeloyl-9-(2,3-dihydroxybutyryl) heliotridine, 7-tigloylheliotridine, rinderine, 7-angeloylrinderine, trachelanthamine, viridiflorine.[67,83,84]
C. pictumEchinatine, heliosupine, pictumine.[85]
C. viridiforumHeliosupine, viridiflorine.[86]
Echium amoenumEchimidine, echimidine isomer (tigloyl), 7-angeloylretronecine, 7-tigloylretronecine.[87]
E. angustifoliumEchimidine[88]
E. diffusumHeliotridine or retronecine esters.[28]
E. glomeratum7-Angeloylretronecine, 9-angeloylretronecine, (7S,8R)petranine, (7S,8S)petranine.[89]
E. horridumEchimidine, echimidine isomer (tigloyl), lycopsamine, 7-acetyllycopsamine, 7-angeloyllycopsamine, 7-tigloyllycopsamine, 7-angeloylretronecine, 7-tigloylretronecine, 7-angeloyl-9-(2-methylbutyryl)retronecine, 7-tigloyl-9-(2-methylbutyryl) retronecine, 7-angeloyl-9-(2, 3-dihydroxybutyryl)retronecine, 7-tigloyl-9-(2, 3-dihydroxybutyryl)retronecine, uplandicine.[90]
E. humileEchimidine, echihumiline, lycopsamine, 7-acetyllycopsamine, 7-senecioyllycopsamine, pycnanthine, 7-seneioylretronecine, 9-seneioylretronecine, 7-(2-methylutyryl)retronecine, 7-(methybutyryl)-9-(2,3-dihydroxybutyryl)retronecine, 7-(2-methybutyryl)-9-echimidinylretronecine.[91]
E. hypertropicumEchimidine, echihumiline, 7-(2-methylbutyryl)-9-echimidinylretronecine, 7-senecioylretronecine, 9-angeloylretronecine, lycopsamine, 7-acetyl-lycopsamine[92]
E. italicumEchimidine[28]
E. lycopsis (=E. plantagineum)Echimidine, echiumine, uplandicine, lycopsamine, intermedine, echimplatine, echiuplatine, 3'-acetylintermedine, 3'-acetyllycopsamine, 3'-acetylechiumine, 9-angeloylretronecine, leptanthine.[4,93,94]
E. pininanaEchimidine, ehiupinine, 3'-aetylintermedine, hydroxymyoscorpine, myoscorpine.[95]
E. rauwolfiiEchimidine, echimidine isomer (tigloyl), 7-acetyllycopsamine, 7-angeloyllycopsamine, 7-tigloyllycopsamine, 7-angeloylretronecine, 7-tigloylretronecine, 7-angeloyl-9-(2-methylbutyryl)retronecine, 7-tigloyl-9-(2-methylbutyryl)retronecine, 7-angeloyl-9-(2, 3-dihydroxybutyryl)retronecine, 7-tigloyl-9-(2, 3-dihydroxybutyryl)retronecine, uplandicine.[90]
E. sericeumEchimidine, symlandine (or symphytine).[54]
E. setosumEchimidine, echimidine isomer (tigloyl), 7-angeloylretronecine, 7-tigloylretronecine, 9-angeloylretronecine, 9-tigloylretronecine, 7-angeloyl-9-(2-methylbutryl) retronecine, 7-tigloyl-9-(2-methylbutryl) retronecine, 7-angeloyl-9-(2,3-dimethylbutryl) retronecine, 7-angeloyl-9-(2,3-dihydroxybutryl) retronecine, uplandicine.[96]
E. simplex7-Angeloylretronecine, 9-angeloylretronecine.[61]
E. stenosiphon Webb subsp. stenosiphonEchimidine, 7-(2-methylbutyryl)-9-echimidinylretronecine[92]
E. tuberculatumEchimidine,7-angeloyl-9-viridiflorylretronecine, 7-viridiflorylretronecine.[60]
E. vulgareAsperumine, heliosupine, 3'-acetylheliosupine, Echinatine, echiuplantine, leptanthine, echimiplantine, echivulgarine, vulgarine, 7-O-acetylvulgarine, echimidine, echimidine isomer (tigloyl ?), 3'-acetylechimidine, 5'-acetylechimidine, echihumiline, retronecine, 7-angeloylretronecine, 9-angeloylretronecine, 7-tigloylretronecine, 9-tigloylretronecine, 7-(2-methylbutyryl) retronecine, 9-(2-methylbutyryl) retronecine, 7-angeloyl-9-(2-methylbutryl) retronecine, 7-tigloyl-9-(2-methylbutryl) retronecine, 7-angeloyl-9-(2, 3-di methylbutryl) retronecine, 7-tigloyl-9-(2, 3-dihydroxybutryl)retronecine, uplandicine[11,96,97,98]
E. wildprettiEchimidine and its N-oxide.[99]
Ehretia asperaEhretinine[100]
Eritrichium rupestre7-Angeloylretronecine, 7-angeloyl-9-viridiflorylretronecine, 7-viridiflorylretronecine[60]
Hackelia californicaHackelidine, longitubine, 7-acetylhackelidine, 9-latifolylretronecine, 7-acetyl-9-latifolylretronecine[101,102]
H. floribundaLatifoline and its N-oxide.[103]
H. longitubaLatifoline, neolatifoline, longitubine, 7-angeloylretronecie, 9-angeloylretronecine.[104]
Heliotropium acutifoliumHeliotrine[105]
H. amplexicauleIndicine[29]
H. angiospermumSubulacine, lindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. arbainenseEuropine, heliotrine, lasiocarpine.[71]
H. arborescens (=H. peruvianum)Indicine, 3'-acetylindicine, lasiocarpine.[107]
H. arguzioidesHeliotrine, trichodesmine.[28]
H. bacciferumEuropine, heliotrine, heleurine and their N-oxides, supinine.[108,109]
H. boveiEuropine, 7-acetyleuropine, lasiocarpine, 5'-acetyllasiocarpine, lasiocarpine N-oxide, 5'-acetyllasiocarpine N-oxide.[110]
H. bracteatumHelibractinecine, retronecine, helibracteatinine, helibracteatine[111,112]
H. bursiferum7-Angeloylretronecine.[113]
H. circinatum7-angeloylheliotrine, echinatine, europine, heleurine, heliotrine, lasiocarpine.[114]
H. confertifoliumlindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. crassifoliumIlamine, europine and their N-oxides.[115]
H. curassavicumCoromandaline, coromandalinine, curassavine, curassavinine, curassanecine, heliocurassavine, heliocurassavinine, heliocurassavicine, heliocoromandaline, heliovicine, 7-angeloylheliotridine, trachelanhamidine, retronecine, supinidine.[106,116,117,118]
H. curassavicum var. argentium9-(3'-isovaleryl) viridifloryl retronecine, 9-(3'-acetyl) viridifloryl retronecine.[119]
H. curassavicum var. curassavicum9-(3'-isovaleryl) viridifloryl retronecine, 9-(3'-acetyl) viridifloryl retronecine.[119]
H. dasycarpumheliotrine[120]
H. digynum (H. luteum)Europine, heliotrine, 7-angeloylheliotrine, lasiocarpine.[121]
H. disciformeHeliotrine, 2'-actylheliotrine, heliotrine N-oxide, heleurine, heliorine N-oxide.[122]
H. dissitiflorumHeliotrine, heliotrine N-oxide, europine, 5'-deoxylasiocarpine.[123]
H. eichwaldiiHeliotrine, 7-angeloylheliotrine, lasiocarpine.[124]
H. esfandiariiEuropine, europine N-oxide.[125]
H. europaeumEuropine, acetyleuropine, heleurine, heliotrine, 7-angeloylheliotrine, lasiocarpine, 6-acetyllasiocarpine, heliotrine N-oxide, dehydroheliotrine, 5'-acetyllasiocarpine N-oxide, N-(dihydropyrrolizinomethyl)-heliotrine, supinine.[126,127]
H. floridumFloridine, floridinine, floridimine, heliovicine, 3'-acetyltrachelanthamine.[128]
H. foliosisimumlindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. fruticosumlindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. hirsutissimumEuropine, heliotrine, heleurine, lasiocarpine, 3'-acetyllasiocarpine, 5'-acetyllasiocarpine, supinine, N-oxides of acetylasiocarpine, 3'-acetyleheliosupine.[29,129]
H. indicumEchinatine, helindicine, heliotrine, heleurine, indicine, acetylindicine, indicinine, lasiocarpine, lycopsamine, rinderine, supinine, lindelofidine, retronecine, supinidine, trachelanthamine.[106,116,130,131,132]
H. keralenseIntermedine, isolycopsamine, retronesine.[133]
H. lasiocarpumHeliotrine, lasiocarpine.[29]
H. marifoliumEuropine, heliotrine, indicine, lasiocarpine.[29]
H. maris mortuiEuropine, lasiocarpine.[29,71]
H. megalanthumLycopsamine, megalanthonine.[134]
H. mollesubulacine[29]
H. olgaeHeliotrine, incanine.[135]
H. ovalifoliumHeliofoline, retronecine.[136]
H. peruvianumRinderine[29]
H. popovii subsp. gillianumHeliotrine[28]
H. procumbensLindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. queretaroanumLindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. racemosumLindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. ramosissimumHeliotrine[28]
H. rotundifoliumEuropine, 5'-acetyleuropine, heliotrine, lasiocarpine.[137,138]
H. scabrumHeliscabine, retronecine.[139]
H. sesseiLindelofidine, retronecine, supinidine, trachelanthamidine.[106]
H. spathulatumAmabiline, coromandaline, coromandalinine, heliovicine, curassavinine, curassavine, heliospathine, heliospathuline, lindelofidine, retronecine, supinidine, trachelanthamidine.[116,140]
H. steudneriLycopsamine[27]
H. strigosumStrigosine, trachelanthamidine[25,141]
H. suaveolensEchinatine, europine, heliotrine, lasiocarpine.[29]
H. subulatumSubulacine; retronecine, heliotrine, 7-angeloylheliotridine[142]
H. supinumEchinatine, heliosupine, heliotrine, 7-angeloylheliotridine (and its trachelanthic and viridifloric esters), lasiocarpine, supinine.[27,143]
H. ternatumsubulacine[27]
H. transalpinumIntermedine, indicine, lycopsamine, rinderine, 3'-acetylrinderine, supinine.[144]
H. transalpinum var. transalpinumTransalpinecine, subulacine.[145]
H. transoxanumHeliotrine[105]
H. wigginsiiLindelofidine, retronecine, supinidine, trachelanthamidine.[106]
Lappula glochidiataEchinatine[146]
L. intermedia (Echinospermum intermedium)Lasiocarpine[147]
L. myosotisIntermedine, lycopsamine , 7-acetylintermedine, 7-acetyllycopsamine.[35,148]
L. spinocarposAmabiline, intermedine, 7-angeloylheiotridine, 9- heliotrinoylretronecine, lycopsamine, 7-acetyllycopsamine, retronecine, trachelanthamine, supinine, viridiflorine.[40]
Lindelofia anchusoides (L. macrostyla)Lindelofamine, lindelofine.[28]
L. angustifoliaAmabiline, echinatine[78]
L. longifloraEchinatine and its N-oxide.[149]
L. olgaeViridiflorine[150]
L. pterocarpaViridiflorine[151]
L. spectabilisEchinatine, 3'-acetylechinatine, monocorotaline.[124]
L. stylosaEchinatine, lindelofine, viridiflorine.[135]
L. tschimganicaEchinatine, carategine, viridiflorine.[152]
Lithospermum canesensCanesine, canescenine, 3'-acetycanesine, 3'-acetylcanescenine, lycopsamine, 7-acetyllycopsamine, 7-acetylintermedine.[153,154]
L. erythrorhizonIntermedine, myoscorpine, hydroxymyoscorpine.[155]
L. officinaleLithosenine, acetyllithosenine.[156]
L. purpureocoeruleumLycopsamine[60]
Macrotomia echioidesMacrotomine[28]
Mertensia bakeriLycopsamine[157]
M. ciliataIntermedine, lycopsamine.[157]
Messerschmidia argenteaIndicine, 3'-acetylindicine, and their N-oxide.[158]
M. sibiricaLycopsamine, 9-angeloylretronecine.[28]
Moltikiopsis ciliata (Lithospermum callosum)Echinatine, heliotrine.[108]
Myosotis scorpioides (=M. palustris)Myoscorpine, symphytine, scorpioidine, 7-acetylscorpioidine.[159]
M. sylvaticaHeliosupine, 3'-acetylheliosupine, 9-angeloylretronecine, trachelanthamine.[25]
Neatostema apulumAmabiline, lycopsamine and their N-oxides.[160]
Nonnea lutea7-viridiflorylretronecine[60]
N. setosa7-viridiflorylretronecine[60]
Omphalodes vernaIsoretronocanol or its isomer.[27]
Onosma alboroseaIntermedine, lycopsamine, 7-acetylintermedine, 7-acetylycopsamine. [161]
O. alboroseum × sanguinolentum9-Angeloylretronecine, echimidine, lycopsamine, intermedine, 7-acetylintermedine, 7-acetylycopsamine.[161,162]
O. arenaria7-Acetyllycopsamine, 5,6-diydro-7,9-dimethoxy-7H-pyrrolizine, 7-acetylretronecine, 7-acetyl-9-(2-methylbutryl) retronecine, 7-acetyl-9-(2,3-dimethylbutryl) retronecine, 7-acetyl-9-(2-hydroxy-3-methylbutryl) retronecine, 7-acetyl-9-(2,3-dihydroxybutryl) retronecine, 9-(butyryl-2-ene) supinidine, 3'-acetylsupinine, uplandicine.[163]
O. arenaria subsp. penninaIntermedine, lycopsamine, 7-acetylintermedine, 7-acetylycopsamine.[161]
O. erectaN-oxides of 7-O-acetylechinatine, viridinatine, stereoisomer, 7-epi-echimiplatine, onosmerectine.[164]
O. hetrophyllumHelioridine, 1-methylene-8α-pyrrolizidine.[165]
O. leptanthaEchihumiline, 3’-acetylechihumiline, leptanthine and their N-oxides.[166]
O. stellulatumEchimidine, 7-viridiflorylretronecine, heliospathuline, leptanthine, lyopsamine and heir N-oxides, 7-acetylintermedine, dihydroechinatine, trahelanthamine, uplandicine.[60,167]
Paracaryum himalayenseViridiflorine[151]
P. intermedium7-Angeloylheliotridine, 7-senecioylheliotridine, rinderine, 7-angeloylrindrine, 7-senecioylrinderine, viridiflorine.[40]
P. regulosumEchinatine, heliosupine, 7-angeloylheliotridine, rinderine, viridiflorine.[40]
Paracynoglossum imeretinumEchinatine, heliosupine.[29]
Pulmonaria obscuraIntermedine, lycopsamine, 7-acetylintermedine, 7-acetylycopsamine.[168]
Rindera austroechinataEchinatine, rinderine, 7-angeloylheliotridine[57,152]
R. baldschuanicaEchinatine, rinderine, trachelanthamine, turkestanine[152]
R. cyclodontaEchinatine[120]
R. echinataEchinatine, trachelanthamine[120]
R. oblongifoliaCerategine, echinatine, turkestanine.[152]
R. umbellata7-Angeloyl-9-(+)-trachelanthyl heliotridine, lindelofine, punctanecine, 7-angeloyl heliotridane, 7-angeloyl heliotridine, heliosupine, 9-(+)-trachelanthyl-laburnine, echinatine. [169]
Solenanthus circinnatusEchinatine[151]
S. coronatusEchinatine[135]
S. karateginusCerategine, ehinatine.[151]
S. turkestanicusRinderine, turkestanine.[135,150]
Symphytum aintabicumEchimidine[170]
S. asperumEchimidine, symphytine, asperumine, ehinatine, heliosupine, acetylechimidine (or its isomer), aetyllyopsamine (or its isomer), symviridine[171,172]
S. bohemiumEchimidine, lycopsamine, 7-acetyllycopsamine, symphytine.[173]
S. caucasiumAsperumine, echimidine, echinatine, heliotrine, lasiocarpine.[174]
S. consolidumEchimidine, symphytine.[175]
S. grandiflorumEchimidine, lycopsamine, symphytine.[176]
S. ibericumEchimidine, lycopsamine, symphytine.[176]
S. officinaleLycopsamine, 7-acetyllycopsamine, symphytine, echimidine, echinatine, heliosupine, intermedine, 7-acetylintermedine, viridiflorine, symviridine.[17,162,171,172,177,178,179]
S. orientaleAnadoline, echimidine, symphytine.[28]
S. peregrinumIntermedine, 7-acetylintermedine, lycopsamine, 7-acetyllycopsamine, symphytine.[27]
S. sylvaticum subsp. sepulcrale var. sepulcraleEchimidine N-oxide[170]
S. tanaienseEchimidine, lycopsamine, 7-acetyllycopsamine, symphytine.[173]
S. tuberosum7-Angeloylretronecine; anadoline, echimidine, lycopsamine, 7-acetyllycopsamine, symphytine.[28,162,176]
S × uplandicumEchimidine, intermedine, 7-acetylintermedine lycopsamine, 7-acetyllycopsamine, symphytine, symlandine, symviridine, uplandicine.[172,180]
Tournefortia sarmentosaSupinine[28]
T. sibiricaTurneforcine[29]
T. sogdianaEchinatine[57]
Trahlenthus hissaricusTrachelanthine, trachelanthamine, viridiforine.[29]
T. korolkoviiTrachelanthine, trachelanthamidine, trachelanthamine.[57,150]
Trichodesma africanumEuropine, intermedine, lycopsamine, trichodesmine, retronecine, viridiflorine[40,71,181]
T. ehrenbergiiSenkirkine, supinine.[54]
T. incanumInanine, trihodesmine.[46]
T. zeylanicumSupinine[182]
Ulugbekia tschimganicaUluganine[183]
Table 2. Alkaloid composition of investigated species of Boraginaceae.
Table 2. Alkaloid composition of investigated species of Boraginaceae.
CompoundsSourcesReferences
3'-AcetylcanesineLithospermum canesens[153,154]
3'-AcetylcanescenineLithospermum canesens[153,154]
7-Acetyl-9-curassavoylheliotridineAnchusa milleri[40]
7-Acetyl-9-(2,3-dihydroxybutryl) retronecineOnosma arenaria[163]
7-Acetyl-9-(2-dimethylbutryl) retronecineOnosma arenaria[163]
3'-AcetylechinatineCynoglossum creticum[70]
Cynoglossum officinale[67]
Lindelofia spectabilis[124]
Messerschmidia argentea[158]
7-AcetylechinatineCynoglossum amabile[67]
Cynoglossum officinale[67,84]
Onosma erecta[69]
3'- AcetylechihumilineOnosma leptantha[166]
3'-AcetylechiumineAmsinckia menziessi var. intermedia[42]
Cryptantha clevelandii[63]
3'-AcetylechimidineEchium vulgare[96]
5'-AcetylechimidineEchium vulgare[11]
5'-AcetyleuropineHeliotropium disciforme[122]
Heliotropium rotundifloium[138]
7-AcetyleuropineHeliotropium bovi[110]
3'-AcetylfurcatineAmsinckia carinata[42]
Amsinckia furacata[42]
3'-AcetylheliosupineCynoglossum creticum[70]
Cynoglossum officinale[67,83]
Heliotropium hirsutissimum[129]
7-Acetyl-9-(2-hydroxy-3-methylbutryl) retronecineOnosma arenaria[163]
3'-AcetylindicineHeliotropium arborescens (H. peruvianum)[28]
Messerschmidia argentea[158]
3'-AcetylintermedineAmsinckia eastwoodiae[42]
Amsinckia lycopsoides[42]
Amsinckia lycopsoides × menziesii var. intermedia[42]
Amsinckia menziesii var. intermedia[43]
Amsinckia retrosa[42]
Amsinckia spectabilis var. microcarpa[42]
Amsinckia spectabilis var. spectabilis[42]
Amsinckia tessellata[46]
Cryptantha cana[63]
Cryptantha crassipes[64]
Cryptantha clevelandii[63]
Cryptantha flava[63]
Cryptantha leiocarpa[63]
Cryptantha thyrsiflora[63]
Cryptantha virgata[63]
Echium pininana[95]
7-AcetylintermedineAmsinckia carinata[42]
Amsinckia menziesii var. intermedia[42]
Amsinckia tessellata[46]
Anchusa arvensis[40]
Borago officinalis[55]
Cryptantha cana[63]
Cryptantha crassipes[64]
Cryptantha flava[63]
Cryptantha thyrsiflora[63]
Cryptantha virgata[63]
Lappula myostis[35]
Lithospermum canescens[153,154]
Onosma alborosea[161]
Onosma arenaria pennina[161]
Onosma stellulatum[167]
Pulmonaria obscura[168]
Symphytum officinale[171,172,179]
Symphytum peregrinum[27]
Symphytum × uplandicum[180]
5'-AcetyllasiocarpineHeliotropium hirsutissimum[129]
7-Acetyl-9-latifolylretronecineHackelia californica[101]
3'-AcetyllithosenineLithospermum officinale[156]
3'-AcetyllycopsamineAmsinckia grandiflora[42]
Amsinckia lunaris[42]
Amsinckia menziesii[45]
Amsinckia menziesii var. intermedia[42]
Amsinckia tessellata[46]
Amsinckia tessellata var. tessellata[42]
Cerinthe glabra[40]
Cryptantha cana[63]
Cryptantha crassipes[64]
Cryptantha flava[63]
Cryptantha jamesii[66]
Cryptantha thyrsiflora[63]
Echium lycopsis (E. plantagineum)[93]
7-AcetyllycopsamineAmsinckia grandiflora[42]
Amsinckia menziesii[45]
Amsinckia menziesii var. intermedia[42]
Amsinckia tessellata[46]
Amsinckia tessellate var. tessellata[42]
Anchusa arvensis[40]
Anchusa hispida[40]
Anchusa officinalis[48]
Borago officinalis[55]
Cerinthe glabra[40]
Cryptantha cana[63]
Cryptantha crassipes[64]
Cryptantha flava[63]
Cryptantha jamesii[66]
Cryptantha thyrsiflora[63]
Cryptantha virgata[63]
Echium horridum[90]
Echium hypertropicum[92]
Echium humile[91]
Echium rauwolfi[90]
Lappula myostis[35]
Lappula spinocarpos[40]
Lithospermum canesens[153,154]
Onosma alborosea[161]
Onosma arenaria[163]
Onosma arenaria pennina[161]
Pulmonaria obscura[168]
Symphytum bohemium[173]
Symphytum officinale[171,172,179]
Symphytum peregrinum[27]
Symphytum tanaiense[173]
Symphytum tubertosum[28]
Symphytum × uplandicum[180]
7-Acetyl-9-(2-methylbutyryl) retronecineOnosma arenaria[163]
3'-AcetylmyscorpineAmsinckia menziesii var. intermedia[42]
Amsinckia retrosa[42]
7-AcetylretronecineOnosma arenaria[163]
3'-AcetylrinderineCynoglossum columnae[69]
Heliotropium transplinum[144]
7-Acetyl-9-sarracinoyl retronecineAlkanna tinctoria[40]
7-AcetylscorpioidineMyosotis scorpioides[159]
3'-AcetylsupinineOnosma arenaria[163]
3'-AcetyltessellatineAmsinckia tessellata var. tessellata[42]
9-AcetytessellatineAmsinckia grandifkora[42]
Amsinckia lunaris[42]
Amsinckia tessellata var. tessellata[42]
3'-AcetyltrachelanthamineHeliotropium floridum[128]
9-AcetyltrachelanthamineAnchusa arvensis[40]
3'-AcetylviridiflorineAmsinckia tessellata var. gloriosa[42]
9-(3'-Acetyl)viridiflory retronecineHeliotropium curassavicum var. argentinum[119]
Heliotropium curassavicum var. curassavicum[119]
9-(3'-Acetylviridifloryl) turniforcidineA. douglasiana[42]
A. tessellata var. tessellata[42]
7-AcetylvulgarineEchium vulgare[11]
AmabilineAmsinckia douglasina[42]
Amsinckia eastwoodiae[42]
Amsinckia grandiflora[42]
Amsinckia lycopsoides[42]
Amsinckia lycopsodes menziesii var. intermedium[42]
Amsinckia menziesii var intermedium[42]
Amsinckia retrosa[42]
Amsinckia tessellata var. gloriosa[42]
Amsinckia tessellata var. tessellata.[42]
Asperugo procumbens[47]
Borago officinalis[55]
Cryptantha confertiflora[63]
Cryptantha crassipes[64]
Cryptantha virginensis[63]
Cynoglossum amabile[67,68]
Cynoglossum glochidiatum[78]
Heliotropium spathulatum[140]
Lappula spinocarpos[40]
Lindelofia angustiflora[78]
Neatostema apulum[160]
AnadolineSymphytum orientale[28]
Symphytum tuberosum[28]
7α-Angeloyl-1-chloromethy-1,2-dihydropyrrolizidineCynoglossum creticum[70]
7-Angeloyl-9-(2,3-dihydroxybutyryl)heliotridineCynoglossum officinale[67]
7-Angeloyl-9-(2,3-dihydroxybutyryl)retronecineEchium horridum[90]
Echium rauwolfii[90]
Echium setosum[96]
Onosma arenaria[163]
7-Angeloyl-9-(2,3-dihydroxypropanoyl)retronecineAlkanna orientalis[40]
Alkanna tinctoria[40]
7-Angeloyl-1-formyl-6,7-dihydro-5H-pyrrolizidineCynoglossum officinale[67]
7-Angeloyl-9-(hydroxypropenoyl)retronecineAlkanna orientalis[40]
Alkanna tinctoria[40]
7-AngeloylechinatineCynoglossum officinale[67]
7-AngeloylheliotridineAnchusa hispida (Gastrocotyle hispida)[40]
Anchusa milleri[40]
Cynoglossum creticum[70,72]
Cynoglossum latifolium[79]
Cynoglossum officinale[67,84]
Heliotropium curassavicum[117]
Heliotropium supinum[27,143]
Lappula spinocarpos[40]
7-AngeloylheliotridineParacaryum intermedium[40]
Paracaryum regulosum[40]
Rindera austroechinata[57]
7-AngeloylheliotrineHeliotropium circinatum[114]
Heliotropium digynum (H. luteum)[121]
Heliotropium eichwaldii[124]
Heliotropium europaeum[127]
Rindera umbellata[169]
7-AngeloyllycopsamineEchium horridum[90]
Echium rauwolfii[90]
7-Angeloyl-9-(2-methylbutyryl)heliotridineCynoglossum creticum[70]
Cynoglossum offocinale[67]
7-Angeloyl-9-(2-methylbutyryl)retronecineEchium horridum[90]
Echium rauwolfii[90]
7-AngeloylretronecineAlkanna orientalis[40,41]
Alkanna tinctoria (A. tuberculata)[40,184]
Arnebia decumbens[52]
Arnebia euchroma[53]
Cerinthe minor[60]
Cryptantha fendleri[63]
Cryptantha leiocarpa[63]
Echium amoenum[87]
Echium glomeratum[89]
Echium horridum[90]
Echium rauwolfii[90]
Echium setosum[96]
Echium simplex[162]
Echium vulgare[96]
Eritrichium rupestre[60]
Hackelia longituba[104]
Heliotropium bursiferum[113]
Symphytum tuberosum[162]
9-AngeloylretronecineAlkanna orientalis[40,41]
Arnebia decumbens[52]
Cryptantha fendleri[63]
Cryptantha leiocarpa[63]
Cynoglossum amabilie[67]
Echium glomaratum[89]
Echium hypertropicum[92]
Echium setosum[96]
Echium simplex[162]
Echium vulgare[96]
Hackelia longituba[104]
Messerchimidia sibrica[28]
Myosotis sylvatica[25]
7-AngeloylrinderineCynoglossun officinale[67]
9-AngeloyltrachelanthamidineAnchusa arvensis[40]
7-Angeloyl-9-(+)-trachelanthylheliotridineRindera umbellata[169]
9-Angeloyl-7-viridiflorylretronecineCerinthe minor[60]
Cynoglossum amabile[60]
Cynoglossum clandestinum[60]
Echium tuberculatum[60]
Eritrichium rupestre[60]
AsperumineEchium vulgare[98]
Symphytum asperum[172]
Symphytum caucasium[174]
9-(Butyryl-2-ene) supinidineOnosma arenaria[163]
CanescineLithospermum canescens[153,154]
CanescenineLithospermum canescens[153,154]
CarategineLindelofia tschimganica[27]
Rindera oblongifolia[152]
Solanthus karateginus[151]
CoromandalineHeliotropium curassavicum[117,118]
Heliotropium spathulatum[140]
CoromandalinineHeliotropium curassavicum[117]
Heliotropium spathulatum[140]
CryptanthineCryptantha utahensis[65]
CurassanecineHeliotropium curassavicum[117]
CurassavineAnchusa officinalis[49]
Heliotropium curassavicum[117]
Heliotropium spathulatum[140]
CurassavinineHeliotropium curassavicum[117]
Heliotropium spathulatum[140]
9-CurassavorylheliotridineAnchusa milleri[40]
CynaustrineCynoglossum australe[68]
Cynoglossum lanceolatum[78]
Cynoglossum montanum[81]
CynaustralineAmsinckia douglasiana[42]
Cynoglossum australe[68]
Cynoglossum furcatum[73]
Cynoglossum lanceolatum[78]
Cynoglossum montanum[81]
CynoglossamineCynoglossum creticum[72]
DehydroheliotrineHeliotropium europaeum[185]
5-DeoxylasiocarpineHeliotropium dissitiflorum[123]
3',7-DiacetylintermedineAmsinckia menziesii var. intermedia[42]
Amsinckia tessellata[46]
Anchusa arvensis[40]
3',7-DiacetyllycopsamineAmsinckia menziesii [45]
Amsinckia tessellata[46]
3',7-DiacetyllycopsamineAnchusa arvensis[40]
Cerinthe glabra[59]
3',9-DiacetyltessellatineAmsinckia tessellata var. tessellata[42]
5,6-Dihydro-7,9-dimethoxy-7H-pyrrolizineOnosma arenaria[163]
DihydroechinatineOnosma stellulatum[167]
thero-2'',3''-DihydroxyechiumineCryptantha clevelandiiCryptantha inequata[63,65]
Cryptantha leiocarpa[63]
DihydroxytriangularineAlkanna orientalis[40,41]
Alkanna tinctoria[40,41]
DihydroxytriangularicineAlkanna orientalis[40]
Alkanna tinctoria[40]
EchihumilineEchium hypertropicum[92]
Echium humile[91]
Echium vulgare[96]
Onosma leptantha[166]
EchimidineArnebia hispidissima[54]
Cryptantha inequata[65]
Echium amoenum[87]
Echium angustifolium[88]
Echium horridum[90]
Echium humile[91]
Echium hypertropicum[92]
Echium italicum[28]
Echium lycopsis (E. plantagineum)[94]
Echium pininana[95]
Echium rauwolfii[90]
Echium sericeum[54]
Echium. setosum[96]
Echium stenosiphon subsp. 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]
Echimidine isomer (tigloyl)Echium rauwolfii[90]
Echium setosum[96]
Echium vulgare[96]
EchimiplatineCryptantha crassipes[64]
Echium plantagineum[93]
Echium vulgare[11]
EchinatineAsperugo procumbens[47]
Cynoglossum amabile[67,68]
Cynoglossum columnae[69]
Cynoglossum creticum[70,71,72]
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]
EchiumineAmsinckia carinata[42]
Amsinckia eastwoodiae[42]
Amsinckia hispida[44]
Amsinckia intermedia[44]
Amsinckia lycopsoides[44]
Amsinckia menziesii var. intermedia[42]
Cryptantha clevelandii[63]
Cryptantha crassipes[64]
Cryptantha leiocarpa[63]
Echium lycopsis[94]
EchiupineEchium pininana[95]
EchiuplatineCryptantha inequata[65]
Echium plantagineum[93]
Echium vulgare[11]
EchivulgarineEchium vulgare[11]
EhretinineEhretia aspera[100]
2'',3''-EpoxyechiumineCryptantha clevelandii[63]
Cryptantha leiocarpa[63]
Erythro-2'',3''-chloro-2''-hydroxyechiumineCryptantha clevelandii[63]
Cryptantha leiocarpa[63]
7-Epi-echimiplatineOnosma erecta[69]
1α-2α-Epoxy-1β-hydroxymethyl-8α-pyrrolizidineHeliotropium transalpinum var. transalpinum[145]
EuropineHeliotropium 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[137,138]
FloridanineCordia sinensis[62]
FloridimineHeliotropium floridum[128]
FloridineHeliotropium floridum[128]
FloridinineHeliotropium floridum[128]
FurcatineAmsinckia carinata[42]
Amsinckia furacata[42]
Amsinckia vernicosa[42]
HackelidineHackelia californica[102]
HeleurineHeliotropium bacciferum[109]
Heliotropium circinatum[114]
Heliotropium disciforme[122]
Heliotropium europaeum[126,127,186]
Heliotropium hirsutissimum[129]
Heliotropium indicum[131]
HelibracteatineHeliotropium bracteatum[112]
HelibractinecineHeliotropium bracteatum[111]
HelibracteatinecineHeliotropium bracteatum[112]
HelibracteatinineHeliotropium bracteatum[112]
HeliofolineHeliotropium ovalifolium[136]
HelindicineHeliotropium indicum[130]
HeliocoromandalineHeliotropium curassavicum[117]
HeliocurassavineHeliotropium curassavicum[117]
HeliocurassavicineHeliotropium curassavicum[117]
HeliocurassavinineHeliotropium curassavicum[117]
HeliospathineHeliotropium spathulatum[140]
HeliospathulineHeliotropium spathulatum[140]
Onosma stellulatum[167]
HeliosupineCynoglossium creticum[70,71,72]
Cynoglossium macrostylum[80]
Cynoglossium montatum[81]
Cynoglossium officinale[67,83,84]
Cynoglossium pictum[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]
HeliotridineAnchusa milleri[90]
Onosma heterophyllum[165]
Heliotridine 2S-hydroxy-2S(1S-hydroxyethyl0-4-methyl-pentanoyl esterAnchusa strigosa[50]
HeliotrineArenbia 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]
HeliotrineHeliotropium marifolium[29]
Heliotropium olgae[135]
Heliotropium popovii subsp. gillianum[28]
Heliotropium rotundifolum[137,138]
Heliotropium suaveolens[29]
Heliotropium supinum[27,143]
Heliotropium transoxanum[27]
Molyikiopsis ciliate  (Lithospermum callosum)[108]
Symphytum caucasium[174]
HeliovicineHeliotropium spathulatum[140]
HeliscabineHeliotropium scabrum[139]
HydroxymyoscorpineEchium pininana[95]
IlamineHeliotropium crassifolium[115]
IncanineHeliotropium olgae[29]
Trichodesma incanum[46]
IndicineHeliotropium amplexicaule[29]
Heliotropium arborescens  (H. pruvianum)[107]
Heliotropium indicum[130,131]
Heliotropium marifolium[29]
Heliotropium transalpinum[144]
Messerschmidia argentea[158]
IndicinineHeliotropium indicum[130,131]
IsoechinatineCynoglossum furcatum (C. zeylanicum)[75]
IsolycopsamineHeliotropium keralense[190]
Isoretronocanol (or its isomer)Omphalodes verna[27]
9-(3'-Isovaleryl)viridiflory retronecineHeliotropium curassavicum var. argentinum [119]
Heliotropium curassavicum var. curassavicum[119]
IntermedineAmsinckia carinata[42]
Amsinckia douglasiana[42]
Amsinckia eastwoodiae[42]
Amsinckia furacata[42]
Amsinckia. grandiflora[42]
Amsinckia hispida[44]
Amsinckia intermedia[44]
Amsinckia lunaris[42]
Amsinckia lycopsoides[42,44]
Amsinckia lycopsoides × menziesii var. intermedia[42]
Amsinckia menziesii[45]
Amsinckia menziesii var. intermedia[42]
Amsinckia retrosa[42]
IntermedineAmsinckia spectabilis var. microcarpa[42]
Amsinckia spectabilis var. spectabilis[42]
Amsinckia spectabilis var. nicolai[42]
Amsinckia tessellata[46]
Amsinckia tessellata var. gloriosa[42]
Amsinckia tessellata var. tessellata[42]
Amsinckia vernicosa[42]
Anchusa arvensis (Lycopsis arvensis)[40]
Anchusa hispidia (Gastrocotyle hispidia)[40]
Anchusa officinalis[48]
Borago officinalis[55]
Cerinthe minor[61]
Cryptantha cana[63]
Cryptantha clevelandii[63]
Cryptantha confertiflora[63]
Cryptantha flava[63]
Cryptantha inequata[65]
Cryptantha jamesii[66]
Cryptantha leiocarpa[63]
Cryptantha thyrsiflora[63]
Cryptantha virgata[63]
Cryptantha virginiensis[63]
Heliotropium keralense[133]
Heliotropium transalpinum[144]
Lappula myostis[35]
Lappula spinocarpas[40]
Lithospermum erythrorhizon[155]
Mertensia ciliate[157]
Onosma alborosea[161]
Onosma arenaria pennina[161]
Pulmonaria obscura[168]
Symphytum peregrinum[27]
Symphytum × uplandicum[180]
Trichodesma africanum[71]
LactodineCynoglossum furcatum[76,187]
LasiocarpineHeliotropium arbainense[71]
Heliotropium bovei[110]
Heliotropium circinatum[114]
Heliotropium digynum[121]
Heliotropium eichwaldii[124]
Heliotropium europaeum[126,127,186]
Heliotropium hirsutissimum[129]
Heliotropium indicum[130,131]
Heliotropium lasiocarpum[29]
Heliotropium marifolium[29]
Heliotropium maris mortui[137]
Heliotropium rotundifolium[137,138]
Heliotropium suaveolens[29]
Lappula intrmedia[27]
Symphytum caucasium[174]
Symphytum officinale[177]
LatifolineCryptantha fendleri[63]
Cynoglossum latifolium[79]
Hackelia californica[101]
Hackelia floribunda[103]
Hackelia longituba[104]
Lindelofia stylosa[27]
9-LatifolylretronecineHackelia californica[101]
LeptanthineCryptantha crassipes[64]
Echium plantagineum[93]
Echium vulgare[11]
Onosma leptantha[166]
Onosma stellulatum[167]
Lindelofine Amsickia menzesii var. intermedia[42]
Amsickia spectabilis var. microcarpa[42]
Amsickia spectabilis var. spectabilis[42]
Amsickia spectabilis var. nicola[42]
Lindelofia anchusoides (L. macrostyle)[28]
Rindera umbellata[169]
LindelofamineLindelofia anchusoides (L. macrostyle)[28]
LindelofidineHeliotropium angiospermum[106]
Heliotropium confertifolum[106]
Heliotropium curassavicum[106]
Heliotropium foliosissimum[106]
Heliotropium fruticosum[106]
Heliotropium gregii[106]
Heliotropium indicum[106,116]
Heliotropium molle[106]
Heliotropium procumbens[106]
Heliotropium queretaroanum[106]
Heliotropium spathulatum[116]
Heliotropium sessei[106]
Heliotropium racemosum[106]
Heliotropium ternatum[106]
Heliotropium wigginsii[106]
LithosenineLithospermum officinale[156]
LongitubineHackelia californica[101]
Hackelia logituba[104]
LycopsamineAmsinckia carinata[42]
Amsinckia douglasiana[42]
Amsinckia eastwoodiae[42]
Amsinckia furacata[42]
Amsinckia grandiflora[42]
Amsinckia hispida[44]
Amsinckia intermedia[44]
Amsinckia lunaris[42]
Amsinckia lycopsoides[42,44]
Amsinckia lycopsoides × menziesii var. intermedia[42]
Amsinckia menziesii[45]
Amsinckia menziesii var. intermedia[42]
Amsinckia retrosa[42]
Amsinckia spectabilis var. microcarpa[42]
Amsinckia spectabilis var. spectabilis[42]
Amsinckia spectabilis var. nicolai[42]
Amsinckia tessellata[46]
Amsinckia tessellata var. gloriosa[42]
Amsinckia tessellata var. tessellata[42]
Amsinckia vernicosa[42]
Anchusa arvensis (Lycopsis arvensis)[40]
Anchusa hispidia (Gastrocotyle hispidia)[40]
Anchusa officinalis[48]
Arnebia decumbens[52]
Borago officinalis[55]
Cerinthe glabra[59]
Cerinthe minor[61]
Cryptantha cana[63]
Cryptantha confertiflora[63]
Cryptantha flava[63]
Cryptantha inequata[65]
Cryptantha jamesii[66]
Cryptantha thyrsiflora[63]
Cryptantha virgata[63]
Cryptantha virginiensis[63]
Cynoglossum amabile[67]
Echium hypertropicum[92]
Heliotropium transalpinum[144]
Heliotropium megalanthum[134]
Heliotropium steudneri[27]
Lappula myostis[35]
Lappula spinocarpas[40]
Lithospermum purpureocoeruleum[60]
Mertensia bakeri[157]
Mertensia ciliate[157]
Mertensia sibirica[28]
Neatostema apulum[60]
Onosma alborosea[161]
Onosma arenaria pennina[161]
Onosma stellulatum[167]
Pulmonaria obscura[168]
Symphytum bohemium[173]
Symphytum grandiflorum[176]
Symphytum ibericum[176]
Symphytum peregrinum[27]
Symphytum officinale[171,177]
Symphytum tanaiense[173]
Symphytum tuberosum[162,176]
Symphytum × uplandicum[180]
Trichodesma africanum[71]
MacrophyllineCordia myxa[62]
MacrotamineMacrotomia echioides[28]
MegalanthonineHeliotropium megalanthum[134]
MethyechiuplatineCryptantha inequata[65]
1-Methylene-8α-pyrrolizidineOnosma heterophyllum[165]
7-(2-Methylbutyryl)retronecineEchium humile[91]
Echium vulgare[96]
9-(2-Methylbutyryl)retronecineEchium vulgare[96]
7-(2-Methylbutyryl)-9-(2,3-dihydroxybutyryl)retronecineEchium humile[91]
Echium vulgare[96]
7-(2-Methylbutyryl)-9-echimidinyl retronecineEchium humile[91]
Echium hypertropicum[92]
Echium stenosiphon subsp. stenosiphon[92]
Echium vulgare[96]
MonocrotalineArnebia hispidissima[54]
Lindelofia spectabilis[124]
MyoscorpineAmsinckia carinata[42]
Amsinckia menziesii var. intermedia[42]
Amsinckia retrosa[42]
Amsinckia spectabilis var. microcarpa[42]
Echium pininana[95]
Linelfolia erythrorhizon[155]
Myosotis scorpioides[159]
NeocoromandalineCynoglossum furcatum[74]
NeolatifolineCryptantha fendleri[63]
Hackelia logituba[104]
OnosmerectineOnosma erecta[69]
 (7S,8R)PetranineEchium glomeratum[89]
(7S,8S)PetranineEchium glomeratum[89]
PictumineCynoglossum pictum[28]
PlatynecineCryptantha leiocarpa[63]
Platynecine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl esterAnchusa strigosa[50,51]
PunctanecineRindera umbellata[169]
PycnanthineEchium humile[91]
RetronecineAnchusa hispida (Gastrocotyle hispida)[40]
Echium vulgare[96]
Heliotropium angiospermum[106]
Heliotropium confertifolum[106]
Heliotropium curassavicum[106,116]
Heliotropium foliosissimum[106]
Heliotropium fruticosum[106]
Heliotropium gregii[106]
Heliotropium indicum[106,116]
Heliotropium keralense[133]
Heliotropium molle[106]
Heliotropium ovalifolium[136]
Heliotropium procumbens[106]
Heliotropium queretaroanum[106]
Heliotropium racemosum[106]
Heliotropium scabrum[139]
Heliotropium spathulatum[106,116]
Heliotropium sessei[106]
Heliotropium ternatum[106]
Heliotropium wigginsii[106]
Lappula spinocarpos[40]
Trichodesma africanum[40]
Retronecine-7:9- dibenzoateCaccinea glauca[58]
Retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl esterAnchusa strigosa[50,51]
Retronecine 2S-hydroxy-2S(1R-hydroxyethyl)-4-methyl-pentanosyl esterAnchusa strigosa[50,51]
RinderineAnchusa milleri[40]
Arnebia decumbens[52]
Cynoglossum columnae[69]
Cynoglossum creticum[70,72]
Cynoglossum officinale[67,84]
Heliotropium indicum[130,131]
Heliotropium peruvianum[29]
Heliotropium transalpinum[144]
Paracaryum intermedium[40]
Paracaryum regulosum[40]
Rindera austroechinata[57]
Rindera baldschuanica[152]
Solanthus turkestanicus[150]
ScorpioidineMyosotis scorpioides[159]
7-SenecioylhelotridineCynoglossum creticum[70]
Paracarum intermedium[40]
7-SenecioylretronecineAlkanna orientalis[40]
Echium hypertropicum[92]
Echium humile[91]
9-SenecioylretronecineAlkanna orientalis[40]
Echium humile[91]
7-SenecioylrinderineParacaryum intermedium[40]
7-SenecioyllycopsamineEchium humile [91]
SincamidineAmsinckia intermedia[44]
SenkirkineTrichodesma ehrenbergii[54]
StrigosineHeliotopium strigosum[25,141]
SubulacineHeliotopium angiospermum[29]
Heliotopium molle[29]
Heliotopium subulacatum[29]
Heliotopium ternatum[27]
Heliotopium transalpinum var. transalpinum[145]
SupinineAmsinckia carinata[42]
Amsinckia eastwoodiae[42]
Amsinckia furacata[42]
Amsinckia lunaris[42]
Amsinckia lycopsoides[42,44]
Amsinckia lycopsoides × menziesii var. intermedia[42]
Amsinckia menziesii var. intermedia[42]
Amsinckia retrosa[42]
Amsinckia spectabilis var. microcarpa[42]
Amsinckia spectabilis var. spectabilis[42]
Amsinckia spectabilis var. nicolai[42]
Amsinckia tessellate var. gloriosa[42]
Amsinckia tessellate var. tessellate[42]
Anchusa arvensis (Lycopsis arvensis)[40]
Anchusa melleri[40]
Arnebia decumbens[52]
Borago officinalis[55]
Caccina crassifolia[57]
Cerinthe glabra[59]
Cynoglossum amabile[67]
Cynoglossum creticum[70]
Heliotropium bacciferum[109]
Heliotropium europaeum[127]
Heliotropium hirsutissimum[129]
Heliotropium indicum[130,131]
Heliotropium supinum[27,143]
Heliotropium transalpinum[144]
Lappula spinocarpos[40]
Tournefortia samentosa[28]
Trichodesma ehrenbergii[54]
Trichodesma zeylanicum[182]
SupinidineHeliotropium angiospermum[106]
Heliotropium confertifolum[106]
Heliotropium curassavicum[106,116]
Heliotropium foliosissimum[106]
Heliotropium fruticosum[106]
Heliotropium gregii[106]
Heliotropium indicum[106,116]
Heliotropium molle[106]
Heliotropium procumbens[106]
Heliotropium queretaroanum[106]
Heliotropium racemosum[106]
Heliotropium spathulatum[106,116]
Heliotropium sessei[106]
Heliotropium wigginsii[106]
Supinidine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl esterAnchusa strigosa[50,51]
SymlandineAmsinckia menziesii var. inermedia[42]
Echium sericeum[54]
Symphytum × uplandicum[180]
SymphytineMyosotis scorpioides[159]
Symphytum asperum[171]
Symphytum bohemium[173]
Symphytum consolidum[175]
Symphytum grandiflorum[176]
Symphytum ibericum[176]
Symphytum officinale[171,177,178,179]
Symphytum orientale[28]
Symphytum peregrinum[27]
Symphytum tanaiense[173]
Symphytum tuberosum[28,176]
Symphytum × uplandicum[180]
SymviridineSymphytum asperum[172]
Symphytum officinale[172,177]
Symphytum × uplandicum[172]
TessellatineAmsinckia douglasiana[42]
Amsinckia eastwoodiae[42]
Amsinckia furacata[42]
Amsinckia grandiflora[42]
Amsinckia lunaris[42]
Amsinckia lycopsoides[42,44]
Amsinckia lycopsoides × menziesii var. intermedia[42]
Amsinckia menziesii var. intermedia[42]
Amsinckia retrosa[42]
Amsinckia spectabilis var. microcarpa[42]
Amsinckia spectabilis var. nicolai[42]
Amsinckia tessellate var. gloriosa[42]
Amsinckia tessellate var. tessellate[42]
Cryptantha confertiflora[63]
Cryptantha virginiensis[63]
ThesinineBorago officinalis[56]
Thesinine-4'-O-β-D-glucosideBorago officinalis[56]
7-Tigloyl-9-(2-deoxy-2-methyl)echimidinylheliotridinEchiumCynoglossum columnae[69]
7-Tigloyl-9-(2,3-dihydroxybutyryl)retronecineEchium horridum[90]
Echium rauwolfii[90]
Echium setosum[96]
Echium vulgare[96]
7-Tigloyl-9-(2,3-dihydroxypropanoyl)retronecineAlkanna orientalis[40]
Alkanna tincotoria[40]
7-TigloylheliotridineCynoglossum officinale[67]
7-TigloyllycopsamineEchium horridum[90]
Echium rauwolfii[90]
7-Tigloyl-9-(2-methybutyryl)retronecineEchium horridum[90]
Echium rauwolfii[90]
Echium setosum[96]
Echium vulgare[96]
7-TigloylretronecineAlkanna tinctoria[40]
Arnebia decumbens[40]
Echium amoenum[87]
Echium setosum[96]
Echium vulgare[96]
9-TigloylretronecineAlkanna orientalis[40]
Alkanna tincotoria[40]
Arnebia decumbens[52]
Echium horridum[90]
Echium rauwolfii[90]
Echium setosum[96]
Echium vulgare[96]
TrachelanthamidineHeliotropium angiospermum[106]
Heliotropium confertifolum[106]
Heliotropium curassavicum[106,116,118]
Heliotropium foliosissimum[106]
Heliotropium fruticosum[106]
Heliotropium gregii[106]
Heliotropium indicum[106,116]
Heliotropium molle[106]
Heliotropium procumbens[106]
Heliotropium queretaroanum[106]
Heliotropium racemosum[106]
Heliotropium sessei[106]
Heliotropium spathulatum[106,116]
Heliotropium strigosa[25]
Heliotropium wigginsii[106]
TrachelanthamineAnchusa hispida[40]
Cynoglossum clandestinum[60]
Cynoglossum creticum[70]
Cynoglossum officinale[67]
Lappula spinocarpos[40]
Myosotis sylvatica[25]
Onosma stellulatum[167]
Rindera balaschuanica[152]
R. echinata[120]
Trachelanthus hissaricus[29]
Trachelanthus korolkovii[57,150]
TrachelanthineTrachelanthus hissaricus[29]
Trachelanthus korolkovii[150]
7-Trachelanthyl-laburnineRindera umbellata[169]
7-TrachelanthylretronecineAmsinckia vernicosa[42]
TransalpinecineHeliotropium transalpinum var. transalpinum[145]
TriangularineAlkanna orientalis[40]
Alkanna tinctoria[40]
TriangularicineAlkanna orientalis[40]
Alkanna tinctoria[40]
TrichodesmineHeliotropium arguzioides [28]
Trichodesma africanum[40,181]
T. incanum[46]
TurkestanineRindera baldschuanica[152]
Rindera oblongifolia[152]
Solenanthus turkestanicus[135,150]
UplandicineEchium rauwolfii[90]
Echium setosum[96]
Echium vulgare[96]
Onosma arenaria[163]
Onosma stellulatum[167]
Symphytum × uplandicum[180]
UluganineUlugbekia tshimganica[183]
ViridantineCynoglossum furcatum[76,187]
Onosma erecta[69]
ViridiflorineAnchusa milleri[40]
Cynoglossum germanicum[77]
Cynoglossum officinale[40,84]
Cynoglossum viridiforum[97]
Lappula spinocarpus[40]
Lindelofia olgae[150]
Lindelofia pterocarpa[151]
Lindelofia stylosa [135]
Lindelofia tschimganic[152]
Paracaryum intermedium[40]
Paracaryum regulosum[40]
Symphytum officinale[179]
Trachelanthus hissricus[29]
Trichodesma africanum[40]
7-ViridiflorylretronecineEchium tuberculatum[60]
Eritrichium rupestre[60]
Nonnea lutea[60]
Nonnea setosa[60]
Onosma stellulatum[60]
VulgarineEchium vulgare[11]

2. Phytochemical Analysis of PAs

Various analytical techniques have been used for extraction, separation, identification and quantification of PAs. Recently, updated reviews were published [188,189] on the analysis of PAs in plants and foods along with different methods of preparation and extraction of PAs from different matrices including plants are their parts, such as seeds, pollen, but also from honey, body fluids, and insects. In addition to column chromatography and HPLC, droplet counter current chromatography (DCCC) has been used in preparative separation of pyrrolizidine alkaloids [190]. Advantages of this method include total sample recovery, good resolution and high reproducibility. A high-speed CCC was applied for preparative separation and purification of PAs from Amsinckia tessellata, Symphytum spp. and Trichodesma incanum [46]. For analytical purposes high-resolution capillary GLC alone or in combination with mass spectrometry is the method of choice for free PA bases [40,59,67,70,90,91,96,163,191,192,193,194,195]. HPLC and HPLC-MS are also helpful but less sensitive than GLC and GLC-MS [60,93,196,197,198,199]. In addition, the resolution is much lower than for GLC but in HPLC also PA-N-Oxides can be directly analysed. The present review describes the most common analytical tools for the analysis of PAs with an emphasis of mass spectrometry (mostly based on GLC-MS analyses).

2.1. Mass Spectrometry

Mass spectrometry is an important and sensitive tool for the identification and structural determination of PAs. The advantages of mass spectrometry are high sensitivity and possibilities of combination with liquid chromatographic methods (e.g., GLC or HPLC) for the analysis of complex mixtures which usually exist in natural sources. Mass spectral data of PAs have been documented in several publications so that a comprehensive database exists. With respect to PAs, the mass spectra provide the molecular mass, type and structure of necine nucleus (saturation at 1, 2-position), sites of hydroxylation and acylation of the hydroxyl groups (as monoester and/or diester). However, MS alone does not provide all necessary structural information (especially, stereochemistry) necessary for an unambiguous assignment of the structure to an unknown compound. There is no difference between the mass spectra of the epimeric pairs e.g., the spectrum of 7-angeloylretronecine is identical to that of 7-angeloylheliotridine, the OH-groups at C-7 are β and α–oriented, respectively. The same situation exists with the stereoisomer pair echimidine and heliosupine. Echinatine, rinderine (heliotridine bases), lycopsamine, intermedine and indicine (retronecine bases) esterified at C-9 with the stereoisomeric acids, (−)-viridifloric, (+)-trachelanthic, (−)-viridifloric, (+)-trachelanthic and (−)-trachelanthic exhibit almost identical mass spectra (Figure 3, Figure 4, Figure 5, Figure 6, Figure 7, Figure 8, Figure 9, Figure 10, Figure 11, Figure 12, Figure 13, Figure 14 and Figure 15).
Mass spectra of PAs provide important informations about the structure of necine substituents. The 1,2-unsaturated necine esterified at C-9 with a free hydroxyl group at C-7 exhibit a base peak at m/z 138, whereas acylation of C-7 (uplandicine, 7-acetyllycopsamine) provide a base peak at m/z 180. PAs with 1,2-unsaturated necines but without a hydroxyl group at C-7 (as in supinidine type) with an esterification at C-9 results in a base peak m/z 122, while the saturated necine of the same type (trachelanthamidine, isoretroncanol, lindelofidine) shows a base peak at m/z 124. 1,2-unsaturated diester PAs esterified with angelic, tiglic or senecioic at C-7 shows a base peak at m/z 220 [40,42,59,67,70,90,91,96,163,193,200,201]. The fragmentation pathway of this type of PAs starts with the cleavage of the weak allylic ester bond at C-9.
Figure 3. Mass spectrum of retronecine/heliotridin.
Figure 3. Mass spectrum of retronecine/heliotridin.
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Figure 4. Mass spectrum of 9-acetyltrachelanthamidine.
Figure 4. Mass spectrum of 9-acetyltrachelanthamidine.
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Figure 5. Mass spectrum of 7-acetylretronecine/7-acetylheliotridine.
Figure 5. Mass spectrum of 7-acetylretronecine/7-acetylheliotridine.
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Figure 6. Mass spectrum of viridiflorine/trachelanthamine.
Figure 6. Mass spectrum of viridiflorine/trachelanthamine.
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Figure 7. Mass spectrum of 9-angeloyl or 9-tigloylretronecine 9-angeloyl or 9-tigloylheliotridine.
Figure 7. Mass spectrum of 9-angeloyl or 9-tigloylretronecine 9-angeloyl or 9-tigloylheliotridine.
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Figure 8. Mass spectrum of amabiline.
Figure 8. Mass spectrum of amabiline.
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Figure 9. Mass spectrum of 9-curassavoylheliotridine.
Figure 9. Mass spectrum of 9-curassavoylheliotridine.
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Figure 10. Mass spectrum of heliotrine.
Figure 10. Mass spectrum of heliotrine.
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Figure 11. Mass spectrum of lycopsamine/intermedine/indicine/echinatine/rinderine.
Figure 11. Mass spectrum of lycopsamine/intermedine/indicine/echinatine/rinderine.
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Figure 12. Mass spectrum of 7-acetyllycopsamine/7-acetyl intermedine/7-acetyl indicine/ 7-acetyl echinatine/7-acetyl rinderine.
Figure 12. Mass spectrum of 7-acetyllycopsamine/7-acetyl intermedine/7-acetyl indicine/ 7-acetyl echinatine/7-acetyl rinderine.
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Figure 13. Mass spectrum of 3',7-diacetyllycopsamine/3',7-diacetyl intermedine/3',7-diacetyl indicine/3',7-diacetyl echinatine/3',7-diacetyl rinderine.
Figure 13. Mass spectrum of 3',7-diacetyllycopsamine/3',7-diacetyl intermedine/3',7-diacetyl indicine/3',7-diacetyl echinatine/3',7-diacetyl rinderine.
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Figure 14. Mass spectrum of echimidine/heliosupine.
Figure 14. Mass spectrum of echimidine/heliosupine.
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Figure 15. Mass spectrum of 3'-acetylechimidine/3'-acetylheliosupine.
Figure 15. Mass spectrum of 3'-acetylechimidine/3'-acetylheliosupine.
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In our review we have tabulated the MS data useful for the identification and structural studies of PAs in Boraginaceae; Table 3 summarizes the mass spectral data (GLC-MS, LC-MS, direct inlet) of corresponding PAs.
Table 3. Mass data of PAs (mostly derived from gas-liquid chromatography-mass spectrometry (GLC-MS) analyses) for all compounds identified in the Boraginaceae. Compounds are numbered as in Figure 16.
Table 3. Mass data of PAs (mostly derived from gas-liquid chromatography-mass spectrometry (GLC-MS) analyses) for all compounds identified in the Boraginaceae. Compounds are numbered as in Figure 16.
No.AlkaloidRI[M]+Characteristic ions m/z (relative abundance)References
13'-Acetylcanescine-441441(0.7), 426(2.6), 355(2.4), 255(6.3), 238(62.4), 220(18.3), 180(39), 136(47), 120(100), 93(74), 80(20).[154]
23'- Acetylcanescenine-441441(1.2), 426(2.4), 398(1.6), 355(1.2), 255(5.7), 238(58.2), 220(20.3), 180(44.3), 136(43.4), 120(100), 93(80.3), 80(22.1).[154]
37-Acetyl-9-curassavoylheliotridine2275355295(0.1), 268(0.2), 198(8), 181(36), 180(100), 136(22), 121(26), 120(84), 119(12), 95(15), 93(35), 80(17), 67(10), 57(12), 45(9), 43(48).[40]
47-Acetyl-9-(2,3-dihydroxybutryl) retronecine2092299239(3), 181(20), 180(100), 136(20), 120(59), 101(20), 94(32), 93(73), 80(12), 67(5), 55(5), 43(15).[163]
57-Acetyl-9-(2,3-dimethylbutryl) retronecine1947**295235(8), 180(100), 136(20), 120(36), 101(30), 94(30), 93(65), 80(8), 43(42). [163]
63'-Acetylechinatine2220341326(0.1), 298(1), 255(2), 254(2), 181(2), 156(4), 139(21), 138(100), 137(10), 136(10), 120(6), 99(6), 94(20), 93(71), 80(8), 67(5), 43(22).[84]
77-Acetylechinatine2235341341(0.1), 281(2), 198(6), 181(39), 180(100), 136(18), 121(35), 120(70), 119(28), 101(9), 94(18), 93(55), 80(7), 43(33). [67]
83'-Acetylechiumine2245*423423(2), 380(3), 338(3), 337(6), 336(3), 323(2), 280(3), 263(3), 256(2), 238(5), 237(6), 221(34), 220(100), 219(15), 159(5), 141(19), 138(12), 136(54), 121(20), 120(76), 119(34), 106(12), 94(42), 93(56), 83(27), 80(15), 59(3), 55(34), 53(17).[42]
93'-Acetylechimidine2640439439(0.1), 424(0.1), 322(1), 238(2), 221(25), 220(100), 219(3), 138(5), 137(6), 136(49), 121(8), 120(61), 119(28), 106(6(, 94(24), 93(46), 83(14), 59(11), 55(13).[91]
105'-Acetyleuropine-371156(18), 138(100), 94(36), 93(75), 59(74).[138]
117-Acetyleuropine-371371(2.7), 356(1), 311(3), 282(5), 180(100), 120(72), 93(65), 80(17), 59(95).[110]
123'-Acetylfurcatine3188*425223(28), 222(100), 143(10), 136(36), 121(15), 120(82), 94(27), 93(61), 85(21), 80(7), 57(63).[42]
133'-Acetylheliosupine2640439424 (0.1), 321(1), 221 (28), 220(100), 141 (10), 138(4), 137(5), 136 (45), 121(14), 120 (89), 119(82), 106(7), 94 (21), 93(40), 83(11), 80(5), 59(8), 55(11), 43(22).[67]
147-Acetyl-9-(2-hydroxy-3-methylbutryl) retronecine2024**297237(5), 180(100), 136(25), 120(52), 119(20), 101(25), 94(45), 93(95), 80(15), 43(35).[163]
153'-Acetylindicine2195341341(2), 255(2), 181(5), 138(100), 93(48), 43(10).[158]
163'-Acetylintermedine2255341341(5), 298 (4), 255 (16), 139(20),138(100), 137 (12),136 (12), 94 (30), 93 (71), 80 (10), 43 (21).[40]
177-Acetylintermedine2220341296(4), 281(3), 181(40), 180(100), 136(25), 121(30), 120(78), 119(15), 101(19), 95(10), 94(30), 93(73), 80(11), 43(40). [40]
185'-Acetyllasiocarpine-453363, 335, 321, 263, 220(100), 141, 136, 121, 120, 119, 106, 94, 93, 83, 80.[186]
193'-Acetyllithosenine-457457(0.78), 442(2), 339(1), 255(2), 238(100), 237(5), 222(10), 220(25), 138(30), 137(8), 136(49), 121(36), 120(75), 119(36), 95(9), 94(34), 93(57), 80(12).[156]
203'-Acetyllycopsamine2255341341(5), 298(4), 255(16), 139(20), 138(100), 137(12), 136(12), 94 (30), 93(71), 80 (10), 43(21).[40]
217-Acetyllycopsamine2230341341(1), 296(4), 281(3), 181(32), 180(100), 136(20), 121(35), 120(70), 119(11), 101 (19), 95(10), 94 (28), 93(61), 80(10), 43(36).[91]
227-Acetyl-9-(2-methylbutyryl) retronecine1914**281221(12), 195(5), 180(100), 136(25), 120(42), 119(15), 101(35), 94(45), 93(80), 80(13), 67(100), 57(18), 53(5), 43(23).[163]
233'-Acetylmyscorpine3290*423221(30), 220(100), 136(47), 120(67), 119(35), 94(39), 93(51), 83(32), 80(19), 55(39).[42]
247-Acetylretronecine1532**197180(3), 137(12), 111(40), 106(30), 94(20), 80(100), 68(3), 43(30).[163]
253'-Acetylrinderine2222341326(0.1), 298(1), 255(1), 254(0.5), 181(5), 156(5), 139(30), 138(100), 137(17), 136(17), 120(10), 99(10), 95(9), 94(35), 93(95), 80(13), 67(9), 43(36).[70]
267-Acetyl-9-(sarracinoyl) retronecine2125295235(1), 197(32), 196(10), 181(8), 180(55), 179(15), 136(34), 121(12), 120(42), 119 (20), 101(19), 94(40), 93100), 80(15), 67(6), 53(9), 43(20). [40]
277-Acetylscorpioidine-423423(0.8), 181(23), 180(92), 179(17), 136(23), 121(10), 120(57), 119(45), 95(6), 94(35), 93(57), 83(100), 80(15), 55(39), 43(30).[159]
283'-Acetylsupinine2080**325284(.02), 299(10), 136(10), 122(100), 120(48), 108(13), 101(13), 93(50), 80(13), 70(9), 53(6), 43(15).[163]
293'-Acetyltessellatine3064*341341(41), 324(10), 323(10), 299(2), 280(8), 255(2), 254(4), 248(2), 238(2), 237(5), 236(17), 198(8), 181(4), 180(2), 156(7), 154(12), 138(22), 137(28), 136(27), 124(23), 120(63), 111(66), 108(30), 106(61), 99(17), 94(35), 93(14), 80(100), 55(10), 53(10).[42]
309-Acetytessellatine2962*341341(7), 299(6), 282(11), 281(15), 248(3), 238(15), 237(16), 236(14), 198(18), 181(12), 180(10), 179(9), 153(13), 138(49), 136(45), 121(26), 120(100), 119(32), 108(11), 106(12), 94(52), 93(89), 80(28), 53(11).[42]
313'-Acetyltrachelanthamine-327327(1), 284(2), 240(6), 184(6), 142(27), 125(38), 124(100), 84(14), 83(59), 82(54).[128]
329-Acetyltrachelanthamidine1395183140(8), 125(8), 124(100), 110(5), 95(10), 83(50), 82 (27), 55(23).[40]
333'-Acetylviridiflorine2767*327327(3), 284(6), 268(2), 267(2), 241(5), 240(9), 225(4), 184(4), 159(2), 142(21), 140(4), 125(17), 124(100), 83(14), 82(12), 55(19).[42]
349-(3'-Acetylviridifloryl) retronecine-341341(4.7), 255(3), 182(5), 157(4), 138(100), 120(10), 93(92), 85(4), 83(20), 80(16), 43(38).[119]
359-(3'-Acetyl)viridifloryl turneforcidine (or isomer)3050*343343(5), 325(4), 300(12), 299(5), 257(14), 256(50), 212(13), 200(15), 197(14), 159(10), 158(36), 141(19), 140(30), 138(16), 122(21), 120(33), 117(10), 106(12), 96(44), 95(90), 83(11), 82(100), 69(17), 55(32).[42]
367- Acetylvulgarine-439440(M++ 1), 422(40), 380(15), 358(5), 340(65), 296(42), 282(85), 180(100).[11]
37Amabiline1985, 2652*283383(1), 140(8), 123 (30), 122(100), 121(46), 120(51), 108(17), 93(25), 80(13), 70 (17), 53(7), 45(6), 43(19). [67]
38Anadoline-381381(6), 204(6), 167(6), 149(23), 139(22), 138(93), 137(45), 136(33), 120(17), 119(17), 118(13), 117(18), 111(12), 109(15), 100915), 97(17), 95(27), 94(55), 93(88), 85(25), 83(100), 82(17), 81(27), 80(27), 73(14), 71(37), 70(17), 67(27), 57(73), 56(17), 55(83), 54(13), 53(20). [202]
397α-Angeloyl-1-chloromethy-1,2-dihydropyrrolizidine1815255220(40), 172(15), 155(45), 136(23), 130(24), 129(32), 128(63), 121(11), 120(94), 119 (24), 106(30), 94 (100), 93(20), 83(20), 80(17), 67(8), 55(35).[70]
407-Angeloyl-9-(2,3-dihydroxybutyryl)heliotridine2333339339(1), 324(1), 294(1), 239(6), 222(25), 221(25), 220(65), 219(8), 138 (20), 137(10), 136(81), 121(24), 120(100), 119(85), 106(15), 94(50), 93(85), 83(24), 80(18), 75(2), 57(10), 55(25), 45(10).[67]
417-Angeloyl-9-(2,3-dihydroxybutyryl)retronecine2315339339(1), 239(5), 238(5), 237(5), 221(25), 220(99), 219(15), 141(20), 138(10), 137(11), 136 (100), 121(15), 120(83), 119(34), 106(10), 94(55), 93(95), 83(41), 80(20), 75(2), 57(10), 55(40), 45(10).[96]
427-Angeloyl-9-(2,3-dihydroxypropanoyl)retronecine2300325294(0.5), 237(5), 255(9), 221(10), 220(67), 219(16), 141(22), 138(5), 137(11), 136(100), 121(11), 120(57), 119(40), 106(10), 94(62), 93(95), 83(37), 80(17), 55(32).[40]
437-Angeloyl-1-formyl-6,7-dihydro-5H-pyrrolizidine1920233 215(3), 150(100), 134(92), 133(35), 122(4), 106(15), 105(38), 104(15), 83(10), 79(16), 55(20). 46[67]
447-Angeloyl-9-(hydroxypropenoyl)retronecine2053307221(13), 220(95), 207(24), 181(8), 141(30), 137(10), 136(100), 120(53), 119 (24), 106(10), 94(63), 93(77), 83(43), 80(21), 67(9), 55(41), 43 (26). [40]
457-Angeloylechinatine2467381336(2), 281(1), 238(11), 221(42), 220(86), 141(11), 138(11), 137(9), 136(55), 121(78), 120(100), 119(60), 117(4), 106(9), 99(3), 94 (30), 93(52), 83(17), 80(10), 55(17), 45(8), 43(21).[67]
467-Angeloylheliotridine1820237219(1), 154(2), 137(42), 136(20), 124(25), 111(35), 106(86), 94(25), 83(10), 80(100), 68(10), 55(20). [70]
477-Angeloylheliotine-395395(5), 295(7), 220(100), 136(57), 120(80), 119(70), 93(43), 83(34), 59(55), 43(18).[127]
487-Angeloyllycopsamine2460*381381(0.1), 336(0.9), 281(0.5), 238(0.5), 220(100), 136(65), 121(40), 120(90), 94(40), 93(85), 83(50), 80(15), 55(48).[90]
497-Angeloyl-9-(2-methylbutyryl)heliotridine2180321321(0.5), 221(43), 220 (70), 195(5), 141(26), 138(4), 137(9), 136(85), 121(13), 120(100), 119(65), 106(13), 94(59), 93(71), 83 (23), 80(15), 67(4), 57(27), 55(30). [67]
507-Angeloyl-9-(2-methylbutyryl)retronecine2155321221(35), 220(100), 195(5), 141 (25), 138(3), 137(9), 136(90), 121(6), 120(53), 119(20), 106(8), 94(50), 93(70), 83(35), 80(15), 57(20), 55(35).[96]
517-Angeloylretronecine1787237237(2), 219 (3), 204(0.5), 191(1), 154(2), 138(5), 137(23), 136(18), 124(23), 111(38), 106(40), 94(20), 93(6), 83(11), 80(100), 55(22). [96]
529-Angeloylretronecine1797237237(1), 219(0.5), 193(3), 154(16), 138(32), 137(25), 136(10), 126(7), 120(2), 108(2), 94(25), 93(100), 83(8), 80(10), 55(13).[96]
537-Angeloylrinderine2465381381(0.1), 336(2), 281(1), 238(10), 221(34), 220(80), 141(11), 138(10), 137(9), 136(53), 121(70), 120(100), 119(59), 117(4), 106(10), 94(28), 93(50), 83(15), 80(10), 55(17), 45(8), 43(25).[67]
549-Angeloyltrachelamthamidine1700223140(1), 125 (30), 124(100), 123(20), 122(15), 110(4), 95(13), 83(45), 82(16), 70(6), 55(27).[40]
559-Angeloyl-7-viridiflorylretronecine-381220(8.3), 138(7.3), 137(9.8), 136(9.9), 120(28.6), 117(50), 106(29), 94(34), 93(23.1), 91(34.6), 79(40.8), 67(39.6), 64(81.8), 60(31), 58(57), 57(85), 55(100).[60]
56Asperumine-397380, 336, 220, 138, 120.[203]
579-(Butyryl-2-ene) supinidine1674**207180(5), 159(7), 157(7), 122(100), 121(6), 120(23), 108(6), 93(15), 80(17), 71(25), 57(7), 53(11), 45(11), 43(14).[163]
58Canescine-399399(0.4), 384(4), 355(1), 338(0.3), 256(10), 238(66), 220(21), 180(11.6), 136(42), 120(100), 93(65), 80(20).[154]
59Canescenine-399399(0.1), 384(1.6), 355(0.4), 338(0.3), 256(9.6), 238(67.5), 220(20.6), 180(14.7), 136(45.1), 120(100), 93(61.6), 80(20.2).[154]
60Coromandaline-285285(2), 267(7), 241(3), 240(9), 142(65), 125(23), 124(100), 83(28), 82(18).[140]
61Coromandalinine-283283(0.8), 239(0.4), 238(0.3), 140(7), 123(27), 122(100), 121(35), 120(40), 108(13), 94(8), 93(20.5), [140]
62Cryptanthine 353354[M++1](1), 272(2), 254(3), 238(2), 138(2), 120(100), 118(2).[65]
63Curassanecine-157126(14), 98(10), 83(100) 82(23).[117]
64Curassavine-299299(0.7), 281(1.4), 255(2.6), 254(5), 142(80), 125(27), 124(100).[140]
65Curassavinine-297297(0.3), 253(0.1), 252(0.1), 241(0.1), 239(0.1), 140(8), 123(31), 122(100), 121(44), 120(41), 108(13), 94(6.4), 93(20).[140]
669-Curassavoylheliotridine2190313295(2), 269(0.5), 268(0.5), 251(0.5), 226(0.9), 156(8), 139(35), 138(100), 120(15), 111(9), 106(8), 95(25), 94(64), 93(80), 80(28), 67(13), 57(11), 45(8), 43(25).[40]
67Cynaustine-283C15H25NO4, 122(100).[68]
68Cynaustraline (or stereoisomer)2682*285285(2), 267(4), 252(5), 242(1), 241(1), 240(3), 226(1), 142(34), 125(15), 124(100), 83(24), 82(14), 55(25).[42]
69Cynoglossamine-445147(100), 138(27), 119(17), 93(23).[138]
705-Deoxylasiocarpine-395396[M + H] + (2), 295(5.5), 363(1), 220(80), 120(83), 93(68), 83(32).[123]
71/723',7-Diacetylintermedine/3',7-Diacetyllycopsamine2340383340(5), 297(10), 296(10), 181(22), 180(100), 136(18), 121(8), 120(47), 119(20), 101(10), 99(10), 94(18), 93(47), 80(5), 43(30).[40]
733',9-Diacetyltessellatine3090*383383(2), 342, 341(37)(7), 324(21), 323(10), 297(8), 296(6), 280(10), 238(2), 237(6), 236(18), 198(10), 181(7), 180(4), 179(8), 154(14), 153(22), 138(20), 136(49), 121(18), 120(100), 119(55), 108(12), 106(19), 99(13), 94(37), 93(82), 80(25), 53(11).[42]
745,6-Dihydro-7,9-dimethoxy-7H-pyrrolizine1415**181150(90), 134(5), 120(100), 119(35), 106(12), 91(3), 79(5).[163]
75Dihydroechinatine-301MS2, 284, 258, 240, 140, 122, 96.[167]
76thero-2'',3''-Dihydroxyechiumine-415415(0.5), 371(2), 254(56), 210(26), 166(5), 138(30), 136(37), 120(100), 93(70).[63]
77Dihydroxytriangularine2525369338(1), 324 (2), 269(30), 252(30), 237(40), 221(25), 220(100), 219(10), 141(20), 138(8), 137(10), 136(80), 121(20), 120(80), 119(30), 106 (8), 95 (9), 94 (45), 93(81), 83(39), 80(10), 55(28).[40]
78Dihydroxytriangularicine2525369338(0.1), 324 (0.1), 269(4), 252(4), 237(5), 221(24), 220(100), 219(3), 141(28), 138(6), 137(8), 136(67), 121(24), 120(75), 119(35), 106(8), 95(8), 94(47), 93(90), 83(41), 80(11), 55(24). [40]
79Echihumiline2578397397(0.1), 382 (0.2), 352 (0.1), 338(0.1), 321 (0.1), 297 (2), 238 (2), 221 (20), 220 (100), 219 (4), 138 (6), 137 (6), 136 (40), 121 (15), 120 (39), 119 (16), 106 (4), 94 (20), 93 (30), 83 (36), 80 (6), 59 (5), 55 (6).[91]
80Echimidine2560397397(0.1), 382 (0.1), 352 (0.1), 297(2), 221(21), 220(100), 219(5), 138(5), 137(6), 136(48), 121(26), 120(75), 119(30), 106(5), 94(30), 93 (61), 83(39), 80(10), 59(10), 55(25), 43(18).[96]
81Echimidine isomer (tigloyl)2580397397(0.1), 382 (0.1), 297(2), 238(3), 221(21), 220(100), 219(3), 138(5), 137(6), 136(48), 121(28), 120(62), 119(23), 106(5), 94(28), 93 (46), 83(30), 80(10), 59(10), 55(20), 43(18).[96]
82Echinatine2175299284(0.1), 254(1), 156(10), 139(30), 138 (100), 137(7), 136(4), 95(9), 94(25), 93 (46), 80(7), 67(5), 53(3), 43(12).[70]
83Echiumine3178*381 381(0.4), 338(1), 337(1), 336(1), 281(2), 255(1), 238(9), 237(2), 221(35), 220(100), 141(16), 138(8), 136(47), 121(32), 120(69), 119(20), 106(7), 94(39), 93(50), 83(28), 80(17), 59(1), 55(37), 53(9).[42]
84Echiuplatine 381383[M++1](3), 382(68), 365(1), 364(1), 322(2), 320(24), 300(5), 282(7), 280(1), 238(4), 220(51), 138(2), 120(100), 118(2).[65]
85Echiupinine-381381(0.3), 337(1), 336(1), 282(0.2), 281(2), 212(38), 220(100), 136(43), 121(33), 120(55), 119(19), 118(18), 117(14), 103(16), 94(24), 93(47), [95]
86Echivulgarine-479480(M++ 1), 462(35), 418(10), 398(10), 380(90), 336(40), 322(100), 220(70).[11]
87Ehretinine-275275, 140(100), 123, 97.[100]
882'',3''-Epoxyechiumine-397254(9), 237(33), 236(100), 164(17), 157(4), 138(4), 136(19), 121(24), 120(25), 94(27), 93(44), 80(12), 71(4), 43(30). [63]
89Erythro-2'',3''-chloro-2''-hydroxyechiumine-435435(0.5), 274(37), 273(32), 272(92), 254(10), 236(13), 208(9), 138(10), 136(25), 121(26), 120(100), 94(32), 93(45), 80919), 71(19).[63]
901α-2α-Epoxy-1β-hydroxymethyl-8α-pyrrolizidine-155126(4), 124(13), 96(10), 80(4), 71(50, 70(100), 68(10), 67(5), 56(6), 55(65).[106]
91Europine2217329314(1), 256(5), 240(25), 239(20), 156(10), 139(20), 138(100), 120(5), 94(20), 93(50), 80(10), 67(4), 59(20), 43(5).[52]
92Floridanine-441426, 397, 382, 168, 152, 151(100), 150, 149, 123, 122, 110, 96, 94.[62,204]
93Floridimine-301301(1), 239(8), 226(7), 142(36), 124(100), 95(12), 94(10), 83(55), 55(23).[128]
94Floridine-343343(1), 328(2), 284(1), 240(2), 239(3), 225(10), 142(8), 124(100), 83(27).[128]
95Floridinine-301301(1), 242(5), 239(7), 226(5), 167(1), 142(46), 125(19), 124(100), 122(8), 110(6), 96(8), 95(7), 83(36), 82(24), 70(12), 59(12).[128]
96Furcatine3138*383383(0.2), 339(1), 281(1), 240(6), 223(35), 222(100), 143(18), 136(33), 121(27), 120(75), 119(21), 94(44), 93(65), 85(13), 80(19), 74(8), 73(5), 60(1), 57(46).[42]
97Heleurine1970297239(1), 198(3), 181(6), 140(15), 131(6), 123(30), 122(100), 120(60), 119(70), 108(16), 93(17), 80(10), 70(11), 59(26).[109]
98Helibracteatine-255255(0.5), 238(6), 237(1), 224(9), 156(43.4), 155(45.5), 138(16.3), 122(2.3), 111(99.7), 99(31), 98(100), 82(35).[112]
99Helibractinecine-173173(22), 156(4), 155(11), 142(7), 129(10), 124(1), 112(5), 99(83), 98(83), 95(6), 83(7), 82(100).[111]
100Helibracteatinecine-173173(20), 156(4.5), 155(14), 142(3), 129(12), 124(1), 112(5), 99(85), 98(100), 82(83.5).[112]
101Helibracteatinine-255255(2), 238(3), 237(3.5), 224(9), 198(7), 181(60), 156(16), 155(93), 154(10), 124(12), 122(21), 100(23), 98(20), 83(23), 82(100).[112]
102Helifoline-255237(3), 156(5), 138(11), 137(3), 112(27), 111(100), 99(9), 98(42), 94(41), 83(9), 82(20), 80(24).[136]
103Helifolinecine-173155(9.5), 129(67), 124(3), 116(6), 112(8), 98(100), 82(59), 80(10).[136]
104Helindicine-281281(35), 207(100), 191(15), 149(37), 135(33), 109(34), 97(73), 95(55), 83(57), 81(46).[130]
105Heliocoromandaline-285285(1), 267(4), 252(4), 240(6), 142(41), 125(17), 124(100), 84(63), 83(20), 82(15).[117]
106Heliocurassavine-299299(1), 284(1), 281(1), 255(3), 254(10), 252(8), 243(7), 226(8), 142(48), 124(100), 83(56), 82(40).[117]
107Heliocurassavicine-285285(1), 267(3), 252(3), 240(3), 142(49), 125(22), 124(100), 84(63), 83(58), 82(41).[117]
108Heliocurassavinine-285285(1), 267(4), 252(4), 240(3), 142(55), 125(24), 124(100), 84(22), 83(48), 82(48), 81(36).[117]
109Heliospathine-313313(1.3), 269(2), 268(1), 156(12), 139(43), 138(100), 137(15), 120(11), 95(20), 94(57), 93(75), 80(10).[140]
110Heliospathuline-299299(14.7), 282(6), 281(16.5), 238(18), 237(19), 236(20), 156(38), 139(30), 137(36), 136(20), 124(19), 120(60), 111(100), 108(51), 106(63), 94(41), 93(13), 80(78), 45(12). [140]
111Heliosupine2553397382(0.1), 352(0.1), 297(2), 238(4), 221(29), 220(100), 141(11), 138(10), 137(8), 136(50), 121(40), 120(95), 119(70), 106(10), 94(26), 93(52), 83 (12), 80(10), 59(10), 55(15), 43(15). [70]
112Heliotridine1447155138(2), 111(55), 94(18), 80(100), 68(15).[40]
113Heliotridine 2S-hydroxy-2S(1S-hydroxyethyl-4-methyl-pentanoyl ester-313MS2: 269, 270, 224, 156, 138, 120, 94.[50]
114Heliotrine2100313255(0.3), 214(0.5), 197(1), 156(5), 139(22), 138(100), 136(13), 120(7), 94(41), 93(83), 80(40), 59(85).[52]
115Heliovicine-285267(5), 252(5), 240(4), 226(3), 175(1), 142(35), 124(100), 96(11), 95(9), 83(25), 82(20), 55(33).[128]
116Heliscabine-255255(4), 156(42), 138(12), 111(100), 99(33), 98(92), 82(77), 80(10).[139]
117Hydroxymyoscorpine-397397(0.2), 382(0.5), 338(0.1), 297(3.6), 221(21.3), 220(100), 136(40), 121(16), 120(41), 119(16.6), 94(18.4), 93(36).[95]
1187-(Hydroxy-methylbutyryl)-9-viridifloryl retronecine2560**399384(2), 354(0.4), 296(0.3), 282(2), 256(6), 239(21), 238(55), 138(15), 136(21), 121(35), 120(100), 108(2), 101(5), 95(10), 94(20), 93(42), 83(5), 80(6), 73(5), 67(3), 59(12), 55(0.5), 43(25).[59]
119Ilamine-313314(M+ +1, 18), 224(6), 139(3), 122(52), 120(25), 93(20), 80(8), 59(100).[115]
120Incanine-337294(2), 250(4), 222(10), 206(8), 155(5), 136(100), 120(77), 119(85), 94(42), 93(56), 80(26), 53(17), 43(69).[46]
121Indicine2126299255(4), 156(11), 138(100), 93(95).[158]
122 Isoechinatine (9-(+)-viridiflorylheliotridine)-299299(11), 156(10), 139(33), 138(100), 137(14), 94(32), 93(68), 80(18).[75,138]
123Isolycopsamine-299281(12.3), 236(10.3), 138(67), 137(42), 136(34), 124(21), 121(15), 120(70), 119(15), 118(15), 117(14), 111(68), 110(21), 109(11), 108(49), 106(81), 95(17), 94(43), 93(28), 80(100). [133]
124Isoretronocanol enantiomer1883*141141(20), 140(9), 124(13), 110(12), 108(11), 83(100), 82(56), 70(10), 68(11), 55(48).[42]
1259-(3'-Isovaleryl)viridifloryl retronecine-383383(0.2), 255(3), 240(3), 223(5), 20194), 138(100), 120(10), 93(66), 85(28), 80(10), 57(19), 43(10), [119]
126Intermedine2133299156(9), 139(35), 138(100), 137(13), 136(13), 120(10), 95(15), 94(50), 93(80), 80(14), 67(9), 45(7), 43(18).[40]
127Lactodine-227227(9), 138(32), 137(41), 124(15), 111(60), 106(21), 94(44), 80(100). [76,187]
128Lasiocarpine-411396(2), 311(4), 279(5), 221(43), 220(11), 137(20), 136(49), 124(22), 120(74), 119(42), 106(15), 95(49), 93(23), 93(33), 83(39).[71]
129Latifoline-393393(6), 293(9), 221(10), 220(74), 219(35), 137(11), 136(100), 120(49), 119(42), 118(8), 94(33), 93(75), 83(29), 80(17), 67(9).[103,104]
1309-Latifolylretronecine-311312(M+ +1, 40), 195(40), 161(20), 119(100).[101]
131Lepanthine-315MS2: 298, 156, 138, 120, 94.[166,167]
132Lindelofine (or steroisomer)2678*285285(5), 267(5), 252(6), 242(1), 241(1), 240(1), 226(1), 142(30), 125(21), 124(100), 83(26), 82(15), 55(30).[42]
133Lithosenine-415415(0.2), 400(10), 297(8), 256(3), 238(100), 237(15), 222(16), 220(24), 138(30), 137(8), 136(49), 121(36), 120(75), 119(36), 95(9), 94(34), 93(57), 80(12)[156]
134Longitubine-353353(29), 293(12), 181(29), 180(78), 136(75), 120(69), 119(62), 118(15), 106(10), 101(22), 94(58), 93(100), 80(32), 67(17). [104]
135Lycopsamine2145299299(0.5), 254(1), 156(8), 139(31), 138 (100), 137(12), 136(12), 120(10), 108(4), 95(15), 94 (55), 93(84), 80(14), 67(10), 45(8), 43(20).[91]
136Macrophylline-23998, 83(100), 55.[62]
137Megalanthonine-301301(2), 283(2), 256(11), 240(8), 212(19), 158(86), 141(15), 140(43), 138(14), 124(10), 122(18), 114(13), 97(18), 96(44), 95(62), 83(15), 82(100), 55(32).[134]
1381-Methylene-8α-pyrrolizidine1274139139(15), 95(100).[205]
1397-(2-Methylbutyryl)retronecine1760239239(20), 222(2), 154(20), 138(12), 137(12), 136(28), 124(37), 120(20), 111(28), 108(15), 106(28), 94(30), 93(20), 80 (100), 68(10), 57(19). [96]
1409-(2-Methylbutyryl)retronecine1795239239(2), 195(5), 154(3), 138(98), 137(8), 136(5), 120(6), 108(5), 94(60), 93(100), 80 (27), 67(15), 57(30).[96]
1417-(2-Methylbutyryl)-9-(2,3-dihydroxybutyryl)retronecine2285341341(1), 239(10), 223(20), 222(100), 143(18), 138(11), 137(7), 136(50), 121(17), 120(80), 119(30), 106(8), 94(40), 93(83), 85(15), 80(15), 57(30), 45(9).[91]
1427-(2-Methylbutyryl)-9-echimidinyl retronecine2512399399(0.1), 384(0.5), 354(0.5), 297(1), 223(20), 222(100), 221(5), 143(15), 138(8), 137(8), 136(40), 121(30), 120(95), 119(30), 106(9), 94(31), 93 (70), 85(15), 80(15), 67(8), 59(15), 57(28), 45(8), 43(24).[91]
143Monocrotaline2268325236(35), 136(46), 120(100), 119(64), 93(36), 80(12), 43(69).[195]
144Myoscorpine3212*381381(0.2), 338(1), 337(2), 336(2), 281(2), 255(1), 238(9), 237(3), 221(33), 220(100), 141(22), 138(8), 136(46), 121(34), 120(71), 119(22), 106(8), 94(36), 93(55), 83(39), 80(19), 59(4), 55(42), 53(11).[42]
145Neolatifoline-393393(7), 293(11), 221(16), 220(85), 219(31), 137(13), 136(100), 120(43), 119(48), 118(15), 94(39), 93(79), 83(32), 80(16), 67(8).[104]
146(7S,8R)Petranine-285ESIMS (positive mode) m/z 286.11966[89]
147(7S,8S)Petranine-285ESIMS (positive mode) m/z 286.12162[89]
148Platynecine-157113(18), 82(100), 68(18), 67(4), 55(27).[106]
149Platynecine N-Oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl ester-331314, 288, 174, 156, 112.[50]
150Pycnanthine2793397397(0.8), 382(0.4), 354(2), 352(2), 281(3), 254(12), 237(32), 236(100), 235(7), 138(26), 137(14), 136(74), 121(46), 120(77), 119(20), 99(20), 94(50), 93(58), 80(20), 71(20), 58(15), 45(20), 44(22), 43(20).[91]
151Punctanecine-383383(0.2), 368(0.5), 338(3), 296(2), 283(3), 266(4), 240(25), 222(19), 155(13), 140(45), 139(40), 137(73), 123(25), 122(48), 120(14), 96(23), 95(26), 83(27), 82(100).[169,206]
152Retronecine1430
2190*
155155(26), 138(2), 111(55), 94(15), 80(100), 68(15).[40]
153Retronecine dibenzoate2785363363(0), 258(10), 241(20), 136(43), 119(55), 105(100), 94(60), 93(78), 77(35). [207]
154Retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl ester-313MS2: 396, 270, 224, 156, 138.[50]
155Retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-[1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester,-471ESIMS: m/z 472 [M + H]+ , for C24H41NO8[51]
156Rinderine2155299284(0.1), 254(0.6), 156(9), 139(35), 138(100), 137(10), 136(10), 120(5), 95 (12), 94(23), 93(70), 80(12), 67(7), 53(5), 43(16).[70]
157Scorpioidine-381381(7), 199(7), 139(11), 138(69), 137(28), 136(13), 120(9), 101(8), 95(4), 94(21), 93(41), 83(100), 80(9), 67(6), 57(6), 55(34), 53(6), 43(10).[159]
1587-Senecioylhelotridine1870237137(35), 136(18), 124(20), 111(35), 106(90), 94(21), 83(15), 80(100), 68(8), 55(18). [70]
1597-Senecioylretronecine1816237237(4), 154(4), 137(30), 136(16), 124(25), 111(37), 106(40), 94(21), 83(23), 80(100), 68 (8), 55(15).[91]
1609-Senecioylretronecine1833237237(1), 193(2), 155(11), 154(10), 138(23), 137(28), 136(15), 126(9), 109(5), 94(25), 93(100), 83(20), 80(16), 67(6), 55(11).[91]
1617-Senecioylrinderine2515381336(0.1), 221(28), 220(61), 138(10), 137(15), 136(50), 121(75), 120(100), 119(85), 106(23), 95(15), 94(48), 93(72), 83(27), 80(30), 55(40), 43(40).[40]
1627-Senecioyllycopsamine2497381336(0.5), 281(1), 238(5), 221(28), 220(100), 219(4), 141(15), 138(14), 137(12), 136(80), 121(38), 120(70), 119(20), 94(38), 93(61), 83 (76), 80(11), 55(15), 45(8), 43(28). [91]
163Sincamidine-313C16H27NO5(similar to heliotrine)[44]
164Senkirkine2460365365(1), 266(10), 250(6), 222(9), 168(24), 153(41), 80(38), 43(100). [54,195]
165Subulacine-155155(17), 126(4), 124(13), 96(10), 80(4), 71(5), 70(100), 68(10), 56(6), 55(65).[106,208]
166Supinine1978283283(0.2), 140(6), 123(25), 122(100), 121(40), 120(49), 108(11), 93(20), 80(8), 70(7), 53(5), 45(4), 43(12).[70]
167Supinidine1887*139139(40), 138(12), 122(32), 120(14), 111(15), 110(18), 108(30), 94(13), 80(100), 70(4), 68(17), 55(14), 53(17).[42]
168Supinidine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester-313MS2: 296, 270, 224, 156, 138.[50]
169Symlandine3194*381381(0.3), 338(1), 337(2), 336(2), 281(2), 255(1), 238(9), 237(3), 221(30), 220(100), 141(19), 138(10), 136(47), 121(35), 120(72), 119(21), 106(9), 94(36), 93(52), 83(31), 80(17), 59(3), 55(40), 53(12).[42]
170Symphytine3240*381381(0.4), 338(1), 337(1), 336(3), 281(2), 255(1), 238(9), 237(2), 221(33), 220(100), 141(21), 138(7), 136(44), 121(33), 120(70), 119(20), 106(7), 94(36), 93(52), 83(33), 80(18), 59(3), 55(38), 53(12).[42]
171Symviridine-381381(0.3), 337(0.1), 336(0.1), 281(0.2), 221(34.5), 220(100), 136(44.2), 121(22), 120(50), 119(11), 118(15), 117(7.6), 103(10), 95(23.5), 93(44.5).[172]
172Tessellatine2930*299299(7), 281(7), 256(5), 255(3), 248(4), 238(11), 237(9), 236(11), 156(19), 139(25), 138(64), 137(23), 124(16), 120(40), 111(45), 108(29), 106(39), 94(54), 93(40), 80(100), 53(17). [42]
1737-Tigloyl-9-(2,3-dihydroxybutyryl)retronecine2325339239(5), 238(5), 237(8), 221(22), 220(90), 219 (20), 141(20), 138(10), 137(11), 136(100), 121(15), 120(80), 119(35), 106(10), 94(58), 93(90), 83(46), 80(20), 75(2), 57(9), 55(40), 45(10) .[96]
1747-Tigloyl-9-(2,3-dihydroxypropanoyl)retronecine2320325237(8), 225(12), 221(12), 220(70), 141(27), 138(5), 137(12), 136(93), 121(8), 120(55), 119(48), 106(10), 94(59), 93(100), 83(55), 80(18), 55(24).[40]
1757-Tigloylheliotridine1873237237(0.5), 137(55), 136(15), 124(19), 120(5), 111(41), 107(10), 106(100), 94(20), 86(6), 83(12), 80(95), 68(5), 55(19).[67]
1767-Tigloyl-9-( hydroxypropenoyl) retronecine2073307221(14), 220(100), 207(27), 181(10), 141(42), 137(10), 136(95), 120(53), 119(28), 106(10), 94(63), 93(84), 83(50), 80(20), 67(9), 55(37), 43(24).[40]
1777-Tigloyllycopsamine2473*381336(1), 281(1.5), 238(1), 221(20), 220(100), 136(60), 121(30), 120(80), 94(40), 93(70), 83(50), 80(18), 55(40).[90]
1787-Tigloyl-9-(2-methybutyryl)retronecine2170321221(36), 220(100), 195(5), 141(32), 138(2), 137(10), 136(82), 121(6), 120(53), 119(25), 106(10), 94(53), 93(80), 83(40), 80(15), 57(20), 55(33).[96]
1797-Tigloylretronecine1816237237(3), 219 (0.5), 154(2), 138(3), 137(29), 136 (15), 124(25), 120(5), 111(44), 106(50), 94(20), 93(6), 83(15), 80 (100), 55(22). [96]
1809-Tigloylretronecine1843237193(5), 154(15), 138(20), 137(26), 136(13), 126(7), 119(5), 109(4), 94(23), 93(100), 83(10), 80(12), 55(18).[96]
181Trachelanthamidine1853*141141(24), 140(10), 124(15), 110(9), 108(7), 83(100), 82(62), 70(8), 68(8), 55(45).[42]
182Trachelanthamine1970285267(5), 252(4), 240(4), 142(50), 125(18), 124(100), 110(4), 96(6), 83(20), 82(11), 70(6), 55(14), 43(12).[70]
183Trachelanthamidine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester -299ESIMS: m/z 300 [M + H]+, 142, 89, 83, 82, 55.[51]
1847-Trachelanthyl retronecine2899*299299(12), 281(6), 236(11), 156(25), 138(50), 120(47), 111(45), 108(29), 106(40), 94(40), 93(320, 80(100).[42]
185Transalpinecine-17398, 83, 70.[145]
186Triangularine2375335237(23), 236(6), 235(4), 221(5), 220(30), 219(18), 141(12), 137(12), 136(100), 121(28), 120(64), 119(35), 95(12), 94(60), 93(98), 83(58), 80(15), 55(30).[40]
187Triangularicine2394335237(30), 236 (6), 235(3), 221(5), 220(31), 219(10), 141(18), 137(10), 136(83), 121(27), 120(51), 119(40), 95(10), 94(55), 93(100), 83(60), 80(15), 55(25).[40]
188Trichodesmine2388353353(1), 264(56), 222(5), 136(36), 120(100), 93(23), 81(16), 43(40).[195]
189Turneforcidine-157113(20), 82(100), 68(21), 67(6), 55(32).[106]
190Uluganine 399399(2), 384(8), 356(1), 355(3), 354(2).[183]
191Uplandicine2337357357(4), 342(5), 297(23), 281(4), 256(4), 207 (7), 206(52), 181(80), 180 (100), 179 (43), 136(75), 121(49), 120(85), 119 (50), 101(23), 94(55), 93(74), 80(28), 73(74), 59(23), 45(20), 44(69), 43(48).[163]
192Viridinatine-443282(17), 138(41), 137(86), 124(32), 111(70), 106(42), 94(44), 80(100).[76,187]
193Viridiflorine1983285284(0.3), 267(5), 252(5), 240(5), 142 (70), 125 (23), 124 (100), 117(3),  110 (5), 83 (35), 82 (22), 70 (15), 55(25), 43(21).[67]
1949-Viridifloryl turneforcidine (or isomer)2394*301301(0.3), 283(8), 257(8), 256(14), 212(18), 159(21), 158(68), 141(17), 140(50), 138(32), 122(24), 121(12), 120(31), 117(10), 106(13), 96(43), 95(81), 83(20), 82(100), 69(22), 55(40).[42]
195Vulgarine-397398[M+ 1] +, 380(18), 336(5), 316(5), 298(40), 254(15), 240(52), 138(100), 120(14).[11]
The RI reported for DB1 capillary column; * RI for DB-1701 capillary column; ** RI for OV1 capillary column; - not determined.
Figure 16. Pyrrolizidine alkaloid structures in Boraginaceae. Compounds are numbered as in Table 3.
Figure 16. Pyrrolizidine alkaloid structures in Boraginaceae. Compounds are numbered as in Table 3.
Diversity 06 00188 g016

2.1.1. Gas Liquid Chromatography-Mass Spectrometry (GLC-MS)

High resolution Gas-liquid chromatography coupled with mass spectrometry (GLC-MS) has become a valuable and highly sensitive means for separation, convenient identification and quantification of complex PA mixtures, even in minute quantities or in diasteroisomeric forms [40,59,67,70,90,91,96,163,191,192,193,194,195]. The combination of molecular weight, group mass fragmentation pattern and Kovats retention indices, enables an unequivocal identification of most of PA tertiary bases even in trace amounts or of closely related isomers. High resolution gas chromatography-mass spectrometry (HRGC-MS) using the SIM mode was applied to detect trace amounts of 1,2-unsaturated PAs in 55 commercially available pollen products [16]. The detection limit of the overall procedure and the reliable quantitation limit were 0.003 μg g −1 to 0.01 μg g −1. GLC and GLC-MS cannot detect N-oxides, because they are not volatile. PA N-oxides need to be reduced to the free base (for example by reduction with zinc in HCl) as an extra step in the sample preparation to make them suitable for GLC analysis.

2.1.2. Liquid Chromatography-Mass Spectrometry (LC-MS)

Coupling of liquid chromatography (LC) with mass spectrometry (MS) allows a simultaneous determination of PAs and their corresponding N-oxides in a single chromatographic run without the requirement of a reduction step [50]. Quantitative analysis of PA mixtures (e.g., from comfrey, Symphytum officinale) was carried out efficiently using electrospray liquid chromatography-mass spectrometry (LC-MS). The method is based on HPLC coupled to an ion-trap and orbitrap MS with electrospray ionization interface [177]. Plant samples from 9 Boraginaceous species have been screened with gradient HPLC equipped with diode array and electron impact mass spectrometry [60]. Several saturated and 1,2-unsaturated PAs (mainly as N-oxides) were detected using HPLC-ESI-MS in fresh pollen collected from flowers of the PAs producing plants Echium vulgare and E. plantagineum and /or from bee pollen from bees that had foraged on PA plants [12]. The same method has also been used to determine the PA profile in E. plantagineum [93], Cryptantha crassipes [64], and Anchusa strigosa [50]. PAs (N-oxides and free bases) occurring in small amounts could be efficiently analyzed using an RP-HPLC ion trap MS method with an atmospheric pressure chemical ionization (APCA) interface [167].
Most PAs in plants are present as N-oxides or their tertiary bases. The N-oxides of this class are polar, water soluble, non-volatile and thermally labile. Thus, the application of LC-MS to the analysis of PA N-oxides has become a widely applied method [64,177,199,209,210], for example, in honey samples.

2.2. Nuclear Magnetic Resonance (NMR)

For the determination of the type of necine, the sites of ester attachment and the stereochemical orientation of necic acids, NMR methods are essential. An excellent comprehensive review of 1H NMR spectral data of PAs (more than 350 compounds) has been published by Logie et al. [211], in which the most useful shift values for the different types of PAs have been documented. Roeder [212] reported the 13C NMR data of 136 PAs and updated his data in a book chapter of Rizk [28]. After that time, more NMR data have been published for new PAs which are documented in this review.

2.3. Enzyme-Linked Immunoassay

A highly sensitive and specific competitive enzyme-linked immunosorbent assay (ELISA) can be used for detection and quantification of PAs [213,214,215,216]. The limit of detection of this ELISA method was 1.9, 10, 18, 20 and 60 ng for lasiocarpine, lasiocarpine N-oxide, heliotrine, and heliourine N-oxide, respectively [217]. These data suggest that this technique can be an excellent tool to diagnose poisoned animals and identify PA contaminated food items.

3. Tissue Culture

Several Boraginaceae species were subjected to in vitro cultivation and their PA contents have been studied [153,218,219]. PA profiles of Hairy root cultures of Cynoglossum officinale and Symphytum officinale have been established [220]. In these cultures, all PAs are genuinely present as N-oxides. Recently, Abd El-Mawla [221] reported the influence of methyl jasmonate, quercetin and salicylic acid as elicitors of PA production in the hairy root cultures of Echium rauwolfii.

4. Variation of PAs between Plant Organs and Developmental Stages

Distributions of PAs vary within different plant organs. In Heliotropium indicum a tissue-specific PA analysis revealed the presence of PAs in all tissues: highest levels were detected in the inflorescences which contained more than 70% of total plant alkaloids [116,220]; the alkaloid contents of stems, leaves and roots were 3, 7 and 19%, respectively. Young leaves, young inflorescences or seedlings showed high alkaloid levels, reaching 5%–6% dry matter in H. spanthulatum [116]. The total alkaloid contents of the root and rhizome of Pulmonaria obscura lay between 0.026 and 0.158 mg/g dry weight, whereas leaves and inflorescences accumulated only trace amounts of PAs (below 0.4 ng/mg dry weight) [168]. Extreme differences were found in PA levels between different leaves of Cynoglossum officinale [219]. The youngest leaves of the rosette plants had significantly higher PA contents than the oldest leaves (190 times). Alkaloid profiles and contents (total PAs and free bases) in the different plant organs of Paracaryum rugulosum, P. intermedium, Anchusa arvensis, Anchusa milleri, Alkanna orientalis, Alkanna tuberculata, Lappula spinocarpos and Trichodesma africana have been reported [40].
Table 4. 13C NMR data of new pyrrolizidine alkaloids (PAs) in the time frame 1991–2013.
Table 4. 13C NMR data of new pyrrolizidine alkaloids (PAs) in the time frame 1991–2013.
AlkaloidC-1C-2C-3C-5C-6C-7C-8C-9C-1'C-2'C-3'C-4'C-5'C-6'C-7'C-1''C-2''C-3''C-4''C-5''C-6''solventReferences
Necine Base
Helibractinecine82.838.353.452.536.273.771.268.6 CDCL3-CD3OD[111]
Helibracteatinecine82.634.153.052.933.379.773.067.2 CDCL3-CD3OD[112]
Turneforcidine40.832.656.252.837.572.073.765.6 CD3OD-ND3[222]
Transalpinecine82.384.459.255.928.024.672.363.9 CD3OD[145]
Subulacine70.963.454.058.427.126.267.960.2 CD3OD[145]
1α-2α-epoxy-1β-hydroxymethyl-8α-pyrrolizidine83.765.262.356.227.925.072.164.0 CD3OD[145]
Tertiary base and N-oxide alkaloids
3'-Acetylcanescine133.0127.562.653.634.474.475.462.3175.184.372.4-(CO:170.4), (Me: 21.2)17.233.117.217.1171.746.969.129.429.2 CDCL3/D6-DMSO[154]
3'-Acetylcanescenine133.0127.562.653.634.474.475.462.3175.184.373.7-(CO:170.4), (Me: 21.3)16.033.117.814.2171.746.969.129.429.2 CDCL3/D6-DMSO[154]
3’-Acetylechihumiline N-oxide133.0124.979.470.533.973.395.663.0174.785.674.8-(Me: 21.6)61.174.027.326.4166.8116.2161.928.021.0 CD3OD[166]
7-Acetylechinatine N-oxide133.0124.379.070.133.473.895.062.1175.085.272.418.234.018.516.7171.521.1 CD3OD[69]
7-Acetyleuropine135.0128.362.354.430.676.978.862.6174.284.079.2- (OMe:56.8)13.373.426.724.9171.321.5 CDCL3[110]
3'-Acetylindicine132.3130.762.853.036.171.178.563.3174.581.671.8-(CO:170.0), (Me 21.1)14.332.317.216.3 CDCL3[158]
3'-Acetylindicine N-Oxide132.4121.978.069.634.769.695.862.1173.881.972.4-(CO:170.3), (Me: 21.2)14.033.017.316.8 CDCL3[158]
3'-Acetyllithonine132.5128.262.253.033.873.574.861.5172.382.972.1-(CO:169.0), (Me: 20.5)14.772.424.825.9170.547.368.128.828.9 CDCL3[156]
3'-Acetylrinderine135.0128.461.954.234.075.280.462.4174.381.872.5-(CO:110.2), (Me 13.9)21.133.116.817.2 CDCL3[70]
3'-Acetyltrachelanthamine44.730.454.154.925.631.567.867.9174.381.672.2 -(CO: 169.7), (Me: 21.1)13.932.816.717.2 CDCL3[128]
Canescine133.0127.562.653.634.474.475.462.3175.184.369.517.233.117.217.1171.746.969.129.429.2 CDCL3/D6-DMSO[154]
Canescenine133.0127.562.653.634.474.475.462.3175.184.371.116.033.117.814.2171.746.969.129.429.2 CDCL3/D6-DMSO[154]
Cryptanthine133.9125.862.953.934.775.475.660.7167.7127.4139.316.020.6175.477.471.416.722.6 [65]
Echihumiline132.8127.662.053.734.273.776.162.0174.383.169.818.572.426.024.9165.5115.3159.027.720.4 CDCL3[91]
Echimidine isomer133.312963.254.134.874.27662.9174.783.770.018.973.826.525.2167.5128.9138.214.812.3 CDCL3[87]
Echiupinine133.0128.162.353.734.372.875.662.2175.182.968.717.232.917.116.9167.1115.6158.127.520.3 CDCL3[95]
Echiupinine N-oxide131.8128.178.269.134.371.493.760.2174.984.069.416.933.217.517.2166.2114.5160.327.620.6 CDCL3[95]
7-Epi-echimiplatine N-oxide132.4125.979.770.235.871.496.763.6176.186.971.119.075.626.327.0 D2O[164]
2'',3''-Epoxyechiuminenoise128.562.753.634.475.375.462.5175.182.969.417.133.016.917.3noise77.260.013.619.3 CDCL3[63]
Erythro-3''-chloro-2''-hydroxyechiumine132.6127.862.453.734.575.475.862.3173.683.069.416.933.017.117.3175.177.262.817.923.0 CDCL3[63]
Floridine44.231.254.054.025.429.567.666.2173.483.472.7 -(CO: 169.6), (Me: 21.2)15.173.526.224.9 CDCL3[128]
Floridinine43.328.653.854.024.630.668.466.2174.682.569.818.673.925.026.0 CDCL3[128]
Floridimine44.328.754.254.325.330.667.663.2174.784.169.918.673.826.024.9 CDCL3[128]
Helindicine134.2125.362.555.536.770.580.561.7175.684.570.517.334.217.217.6 CD3OD[130]
Heliotridine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester134.0123.562.055.935.070.879.462.2??45.025.223.124.473.9-(8':17.4) CD3OD[50]
Heliscabine81.138.452.852.036.072.869.870.0168.1127.2139.716.020.6 CDCL3[139]
Heliospathine133.1128.962.453.936.170.578.262.2174.584.471.217.438.924.712.1-(8':11.9) CDCL3[140]
Heliospathuline139.1124.262.453.934.876.576.259.3 174.383.872.416.531.915.6 (7'':17.2)CDCL3[140]
Hydroxymyoscorpine132.8128.562.853.734.373.875.762.5174.283.069.618.473.525.924.8167.1128.6137.814.411.9 CDCL3[95]
Isoechinatine (9-(+)-viridiflorylheliotridine) 136.1126.361.754.333.874.779.861.9174.383.971.617.532.217.815.9 CDCL3[72,75]
Iso-lycopsamine139.1123.263.053.434.976.476.559.5 174.182.869.416.533.3817.2 (7'':12.27)CDCL3[133]
Lactodine138.1123.263.854.135.169.476.558.9173.368.416.3 CDCL3[187]
Leptanthine133.7124.661.754.936.370.079.961.6174.885.170.218.074.226.025.4 CD3OD[166]
Lithosenine N-oxide133.7124.078.069.736.371.296.862.5175.586.171.219.175.227.026.3 CD3OD[166]
Lithosenine133.0126.962.253.133.873.474.861.4173.583.468.918.072.524.725.9170.347.568.128.929.0 CDCL3[156]
Megalanthonine36.031.251.154.636.869.572.866.2174.584.172.017.032.015.617.8 CDCL3[134]
Methylechiuplatine133.5128.062.954.034.773.676.161.3171.344.969.744.8172.251.8:OMe27.3166.9127.7139.215.920.6 CDCL3[65]
Myoscorpine133.1128.162.753.834.473.775.862.2175.182.969.317.232.917.116.9167.0128.5137.814.411.9 CDCL3[95]
Myoscorpine N-oxide131.8124.07 8.469.334.372.493.860.114.984.069.416.933.117.517.2166.2127.9139.014.612.0 CDCL3[95]
Onosmerectine N-oxide133.5123.878.669.735.770.796.762.5175.385.774.670.818.726.625.9 CD3OD[164]
(7S, 8R)-Petranine134.4121.170.963.434.770.287.759.8167.5126.9140.316.120.6 68.8 CDCL3[89]
(7S, 8S)-Petranine134.6121.371.263.634.870.688.159.9167.0127.0149.916.320.8 69.1 CDCL3[89]
Platynecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester37.330.673.070.635.870.191.567.3??44.525.323.324.873.9-(8':17.4) CD3OD[50]
Pycnanthine132.8126.062.253.934.272.475.861.7174.483.671.315.832.017.717.0165.5112.4160.166.830.3 CDCL3[91]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester133.2123.862.054.036.770.080.061.0175.482.345.225.323.324.673.9-(8':17.6) CD3OD[51]
Retronecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester133.9123.478.870.035.770.697.262.4175.982.045.025.223.324.673.6-(8':17.7) CD3OD[51]
Retronecine N-oxide 2S-hydroxy-2S-(1R-hydroxyethyl)-4-methyl-pentanoyl ester134.0123.478.870.035.870.697.062.0175.581.044.025.823.924.374.0-(8':16.5) CD3OD[51]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-2S-[(1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester135.4124.062.054.936.670.479.861.7175.782.243.625.224.024.773.4-(8': 7.4)180.081.345.025.223.124.7 (7'':73.6) (8'':17.0)CD3OD[51]
Symviridine133127.862.753.834.372.775.862.3174.483.470.717.132.917.716.0166.9115.5158.227.520.3 CDCL3[172]
Supinidine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester137.7123.076.971.125.228.390.261.2176.282.045.225.223.524.673.3-(8':17.6) CD3OD[51]
Tessellatine138.6124.563.053.434.775.776.059.6 173.183.571.416.931.917.6 (7'':15.7)CDCL3[42]
Threo-2'',3''-dihydroxyechiumine132.9125.063.354.034.874.975.863.0174.983.269.816.933.217.217.2175.478.771.516.522.1 CDCL3[63]
Trachelanthamidine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester48.029.755.955.825.631.371.963.4181.681.844.125.024.025.073.9-(8':17.4) CD3OD[51]
Uplandicine132.7127.762.153.434.073.675.562.2174.283.269.618.573.624.725.9170.221.1--- CDCL3[163]
Viridiflorine44.531.554.554.225.530.067.867.2174.483.671.017.232.117.915.9 [42]
Viridinatine139.3124.264.254.236.777.377.359.4174.182.868.416.233.517.217.3176.283.269.116.834.1218.1 (7'':18.9)CDCL3[187]
Viridinatine N-oxide stereoisomer132.5125.479.570.135.871.396.663.3176.685.970.917.634.618.918.4176.186.272.318.634.218, 17.2
Table 5. 1H NMR data of new PAs of in the time frame 1995–2013.
Table 5. 1H NMR data of new PAs of in the time frame 1995–2013.
AlkaloidH-1H-2H-3H-5H-6H-7H-8H-9H-3'H-4'H-5'H-6'C-7'H-2''H-3''H-4''H-5''solventReferences
Necine Base
Helibractinecine [C8H15NO3] 1.94α 3.13
β 2.93
α 3.07
β 2.91
2.034.503.34α 3.60
β 3.66
CDCL3-CD3OD[111]
Helibracteatinecine [C8H15NO3] 1.63α 3.26
β 2.55
α 3.26
β 2.52
α 1.84
β 2.11
3.943.12α 3.79
β 3.84
CDCL3-CD3OD[112]
Turneforcidine [C8H15NO2]2.53α 1.68
β 2.10
α 3.08
β 2.55
α 3.03
β 2.70
α 2.00
β 1.99
4.183.16α 3.57
β 3.53
CD3OD-ND3[222]
Transalpinecine [C8H15NO3] 4.18α 3.86
β 3.38
α 3.06
β 3.36
α 1.95
β 2.16
α 1.88
β 2.66
3.99α 3.90
β 3.61
CD3OD[145]
Subulacine [C8H15NO2] 3.95α 3.79
β 3.38
α 2.97
3.62
α 1.96
2.24
α 2.19
2.26
4.45α 3.97
β 3.79
CD3OD[145]
1α-2α-epoxy-1β-hydroxymethyl-8α-pyrrolizidine [C8H15NO2] 4.59α 3.81
β 3.89
α 3.23
β 3.50
α 2.08
β 2.23
α 2.00
β 2.30
4.31α 3.93
β 3.69
CD3OD[145]
Tertiary base and N-oxide alkaloids
3'-Acetylcanescine [C22H35NO8] 5.83α 3.95
β 3.38
α 3.33
β 2.65
2.095.384.35α 4.79
β 4.67
5.21-(COMe: 2.00)1.192.000.940.912.45 1.261.26CDCL3/D6-DMSO[154]
3'-Acetylcanescenine [C22H35NO8] 5.83α 3.95
β 3.38
α 3.33
β 2.65
2.095.384.35α 4.74
β 4.73
5.17 -(COMe: 2.03)1.192.000.940.912.45 1.261.26CDCL3/D6-DMSO[154]
3’-Acetylechihumiline N-oxide [C22H33NO9] 6.03α 4.37
β 4.69
3.90 – 3.75 (m)α 2.20
β 2.78
5.764.834.725.46 -(COMe: 1.98)1.34 1.251.355.67-1.922.18CD3OD[166]
3'-Acetylechinatine [C17H27NO6] 5.76α 3.37
β 3.92
α 2.68
β 3.30
α 1.91
β 1.98
4.173.96α 4.78
β 4.96
5.21-(COMe: 2.04)1.292.010.880.96 CDCL3[70]
7-Acetylechinatine N-oxide 6.00α 4.70
β 4.38
α 3.83
β 3.79
α 2.74
β 2.23
5.694.884.783.961.422.170.900.932.06 CD3OD[164]
7-Acetyleuropine [C18H29NO7] 5.81α 4.02
β 3.38
α 3.28
β 2.86
1.935.094.16α 4.93
β 4.87
3.81-(OMe: 3.27)1.27 1.191.312.06 CDCL3[110]
3'-Acetylindicine [C17H27NO6] 5.92α 3.96
β 3.45
α 3.29
β 2.76
α 1.98
β 2.02
4.304.214.805.20 -(COMe: 2.04)1.232.090.950.92 CDCL3[158]
3'-Acetylindicine N-Oxide [C17H27NO7] 5.794.453.73-3.80α 2.01
β 2.62
4.704.664.835.23 -(COMe: 2.03)1.242.050.970.91 CDCL3[158]
3'-Acetyllithosenine [C22H35NO9] 5.75α 3.77
β 3.29
α 3.17
β 2.54
1.965.234.16α 4.68
β 4.59
5.28 -(COMe: 1.87)1.13 1.251.112.33 1.171.17CDCL3[156]
3'-Acetylrinderine [C17H27NO6] 5.76α 3.37
β 3.92
α 2.68
β 3.30
α 1.91
β 1.98
4.213.96α 4.66
β 4.93
5.28 -(COMe: 2.02)1.252.010.920.98 CDCL3[70]
3'-Acetyltrachelanthamine [C17H29NO5]2.09α 1.70
β 2.02
α 3.28
β 2.60
α 3.07
β 2.65
α 1.89
β 1.84
α 2.05
β 1.63
3.384.165.22 -(COMe: 1.97)1.232.020.900.96 CDCL3[128]
Canescine [C20H33NO7] 5.83α 3.95
β 3.38
α 3.33
β 2.65
2.095.384.35α 4.79
β 4.67
4.071.192.000.940.912.45 1.261.26CDCL3/ D6-DMSO[154]
Canescenine [C20H33NO7] 5.83α 3.95
β 3.38
α 3.33
β 2.65
2.095.384.35α 4.74
β 4.73
3.891.192.000.940.912.45 1.261.26CDCL3/ D6-DMSO[154]
Cryptanthine 5.74α 4.0
β 3.37
α 3.40
β 2.61
2.125.34.39α 4.84
β 4.64
-6.11.981.89 3.81.171.24 CDCL3[65]
5'-Deoxylasiocarpine [C21H33NO6] 5.8α 3.50
β 4.18
α 3.00
β 3.40
1.8 5.124.374.883.7 -(OMe: 3.22) 1.212.200.950.94 6.131.951.82CDCL3[123]
Echihumiline [C20H31NO7] 5.87α 3.35
β 3.72
α 2.83
β 2.83
2.095.484.13α 4.65
β 4.96
4.211.26-1.241.315.59-1.902.15CDCL3[91]
Echihumiline N-oxide [C20H31NO8] 5.97α 4.54
β 4.77
α 3.73
β 4.13
α 2.24
β 2.89
5.775.45α 4.71
β 4.94
4.221.27-1.251.305.57-1.922.17CDCL3[91]
Echimidine isomer (tigloyl) [C20H31NO7] 5.81α 3.34
β 3.83
α 2.60
β 3.27
2.055.374.32α 4.60
β 4.86
4.121.21 1.171.26-6.051.911.76CDCL3[87]
7-Epi-echimiplatine N-oxide [C15H25NO7] 5.89α 4.42
β 4.21
α 3.74
β 3.59
α 2.47
β 2.01
4.674.554.784.181.14 1.161.21 D2O[164]
Floridine [C17H29NO6]2.23α 2.15
β 2.15
α 3.75
β 2.77
α 3.48
β 2.65
2.04α 2.20
β 1.70
4.01α 4.16
β 4.27
5.45 -(COMe: 1.98)1.36-1.251.40 CDCL3[128]
Floridinine [C15H27NO5]2.36α 2.08
β 2.20
α 3.51
β 2.66
α 3.24
β 2.85
α 2.0
β 1.94
α 2.15
β 1.63
3.70α 4.20
β 4.53
4.191.27-1.280.96 CDCL3[128]
Floridimine [C15H27NO5]2.30α 2.17
β 2.28
α 3.89
β 2.83
α 3.59
β 2.89
2.11α 2.26
β 1.80
4.30α 4.35
β 4.45
4.261.32-1.281.33 CDCL3[128]
Helibracteatine [C13H21NO4] 1.85α 3.22
β 2.54
α 3.22
β 2.54
α 1.85
β 2.05
4.083.30α 4.35
β 4.46
6.101.991.91 CDCL3 + D2O [112]
Helibracteatinine [C13H21NO4] α 1.80
β 2.10
α 3.35
β 2.78
α 3.20
β 2.60
1.805.093.30α 3.64
β 3.84
6.121.981.88CDCL3 + D2O[112]
Helindicine [C15H23NO4] 5.94α 4.40
β 3.92
α 3.97
β 3.34
2.154.634.90α 4.98
β 4.80
4.051.172.030.950.93 CD3OD[130]
Heliotridine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C16H27NO5] 5.953.70
4.18
3.10
2.64
2.104.524.604.851.74
1.79
1.820.870.993.78-(8':1.15) CD3OD[50]
Heliscabine [C13H21NO4] 1.86α 3.42
β 3.05
α 3.30
β 3.05
2.164.663.64α 4.25
β 4.35
6.101.991.89 CDCL3[139]
Ilamine [C16H27NO5] 5.813.45
4.10
2.62
3.35
1.86 1.66
2.10
4.434.783.811.28 1.311.20 (8-OMe: 3.30) CDCL3[115]
Ilamine N-oxide [C16H27NO6] 5.81α 3.43
β 4.55
α 3.48
β 3.79
α 1.99
β 1.89
2.504.81α 4.85
β 4.69
3.801.26 1.291.22-(8-OMe:3.30) CDCL3[115]
Isoechinatine (9-(+)-Viridiflorylheliotridine) [C15H25NO5] 5.663.30
3.83
2.55
3.22
1.80
1.92
4.133.974.70
5.00
3.921.242.130.890.85 CDCL3[72,75]
Leptanthine [C15H25NO6] 5.90α 3.90
β 4.40
3.902.204.654.954.904.20 – Me 1.981.291.281.32 [166]
Leptanthine N-oxide [C15H25NO7] 6.05α 4.65
β 4.85
4.1 – 4.0 (m)α 2.23
β 2.63
4.835.20α 4.92
β 4.98
4.22 – Me 1.981.281.251.31 [166]
Lactodine [C11H17NO4] 5.68α 3.90
β 3.34
α 3.26
β 2.59
α 1.93
β 1.87
4.104.02α 5.01
β 4.89
4.201.39 CDCL3 + D2O[187]
Lithosenine [C20H33NO8] 5.78α 3.77
β 3.29
α 3.16
β 2.57
1.965.214.20α 4.66
β 4.52
4.031.13 1.171.112.33 1.161.16CDCL3[156]
Megalanthonine [C15H27NO5]2.78α 1.89
β 2.15
α 3.26
β 2.61
α 3.21
β 2.73
α 2.03
β 2.14
4.293.48α 4.09
β 4.46
2.64-2.643.701.34 6.801.961.80CDCL3[134]
Methylechiuplatine [C20H29NO7] 5.77α 3.97
β 3.37
α 3.32
β 2.64
2.095.404.33α 4.68
β 4.62
[65]
Neo coramandaline [C15H27NO4]1.9α 1.85
β 1.55
α 3.20
β 2.50
α 3.05
β 2.64
α 1.85
β 1.55
α 1.90
β 1.35
3.56α 4.30
β 4.20
3.981.232.140.880.92 CDCL3[74]
Onosmerectine N-oxide [C15H25NO7] 5.96α 4.66
β 4.45
3.87α 2.58
β 2.12
4.754.85α 4.92
β 4.88
4.221.261.311.27 CD3O[164]
(7S, 8R)-Petranine [C14H20CINO3] 5.82α 4.55
β 4.77
α 4.09
β 4.35
α 2.48
β 2.70
4.925.364.786.182.001.90 α5.42
β 5.75
CDCL3[89]
(7S, 8S)-Petranine [C14H20CINO3] 5.83α 4.54
β 4.78
α 4.09
β 4.35
α 2.51
β 2.69
4.945.384.886.202.021.90 α5.71
β 5.39
CDCL3[89]
Platynecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C16H29NO6]2.22α 1.90
β 2.33
α 3.30
β 3.89
α 3.61
β 3.87
α 2.07
β 2.14
4.523.84α 4.29
β 3.85
α 1.76
β 1.70
1.820.870.983.78-(8':1.15) CD3OD[50]
Pycnanthine [C20H31NO7] 5.83α 3.55
β 4.06
α 2.80
β 3.50
2.155.474.12α 4.65
β 4.75
3.991.262.150.930.855.92-3.652.06CDCL3[91]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C16H27NO5] 5.96α 3.98
β 4.46
α 3.49
β 3.87
2.194.644.904.951.751.830.880.993.788'-1.17 CD3OD[51]
Retronecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C16H27NO6] 5.93α 4.36
β 4.65
α 3.70
β 3.82
α 2.63
β 2.08
4.724.684.85α 1.73
β 1.80
1.820.880.983.76-(8':1.16) CD3OD[51]
Retronecine N-oxide 2S-hydroxy-2S-(1R-hydroxyethyl)-4-methyl-pentanoyl ester [C16H27NO6] 5.95α 4.36
β 4.60
α 3.70
β 3.85
α 2.60
β 2.08
4.724.694.82α 1.66
β 1.47
1.740.881.003.91-(8':1.22) CD3OD[51]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-2S-[(1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester [C24H41NO8] 5.95α 3.96
β 4.39
α 3.29
β 3.89
2.184.614.914.94α 1.79
β 1.82
1.800.950.993.70-(8':1.16)1.791.85α 1.81
β 0.87
3.77-(6'':1.14)CD3OD[51]
Symviridine [C20H31NO6] 5.84α4.02
β3.43
α 3.40
β 2.68
2.105.414.48α 4.78
β 4.66
3.971.222.130.860.925.57-1.882.12CDCL3[172]
Supinidine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C16H27NO4] 5.90α 4.36
β 4.56
α 3.61
β 3.67
α 2.08
β 2.38
2.50
2.03
4.664.77α 1.73
β 1.80
1.830.880.98 CD3OD[51]
Trachelanthamidine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C16H29NO4]2.281.90
2.27
α 3.22
β 3.48
α 3.74
β 3.12
2.08
2.19
2.25
1.97
3.993.69
3.63
1.77
1.69
1.830.941.003.77-(8':1.15) CD3OD[51]
Uplandicine [C17H27NO7] 5.83α 3.38
β 3.93
α 2.70
β 3.35
2.065.344.43α 4.62
β 4.87
4.141.22-1.261.191.98 CDCL3[163]
Viridinatine [C22H37NO8] 5.71α 3.80
β 3.30
α 3.16
β 2.19
α 1.92
β 1.85
5.484.10α 4.98
β 4.76
3.901.282.150.860.93-3.951.322.14 (6'':0.90) (7'':1.00)CDCL3 + D2O[187]
Viridinatine N-oxide stereoisomer [C22H37NO9] 5.86α 4.51
β 4.22
α 3.73
β 3.61
α 2.45
β 2.00
4.675.574.754.041.041.890.75–0.78-3.931.102.05, 0.81D2O[164]

5. Biological Activity of PAs

5.1. Antimicrobial Activity

The growth of bacterial species, mostly human pathogens such as E. coli, S. pneumoniae, Bacillus subtilis, B. anthracis and Staphylococcus aureus were inhibited by different pure PAs and PA extracts [90,110]. Successive root bark extracts of Cordia gilletii (Boraginaceae) were tested for their antimicrobial activity against 10 strains of bacteria and 1 strain of fungi by broth microdilution and agar diffusion methods. The methanol extract showed direct antimicrobial activity against all tested microorganisms with minimum inhibitory concentrations (MIC) ranging between 125 and 1,000 µg/ml. [223]. Joosten and van Veen [224] discussed the impact of plant-produced PAs on plant-associated microorganisms, their detoxification by microorganisms and the ecological consequences of this activity.

5.2. Sequestration in Insects and Antifeedant Properties

Several insects are PA specialists which not only tolerate PAs of their host plants but use them for their own chemical defence against predators, as morphogens and even as pheromones [101,144,225,226,227,228,229,230,231]. Defensive PAs can be obtained as larvae from food plants and as adults via nectar. PA sequestering insects often show aposematic colouration. Several moths and butterflies use unsaturated PAs to produce dihydropyrrolizidines with pheromone activity [110]. In some moths PAs are morphogens inducing the formation of large coremata in males, which function as pheromone emitting organs. A recent review published by Macel [232], threw light on the dual role PAs in plant-insect interactions.
The antifeedant activity of six PAs isolated from Anchusa strigosa towards the generalist herbivore Spodoptera exigua and the cabbage specialist Pieris brassicae was evaluated [50]. 1,2-Unsaturated PAs (e.g., retronecine 2S-hydroxy (1S-hydroxyethyl)-4-methyl-pentanoyl ester and its N-oxide) reduced feeding by P. brassicae by 52 and 68%, respectively compared to control. However, the alkaloids lacking to 1,2-double bond (trachelanthamidine ester and platynecine ester) showed no deterrent activity.

5.3. Biological Importance

Toxicity of 1,2-unsaturated PAs as hepatotoxic, pulmotoxic, hemolytic, antimitotic, teratogenic, mutagenic and carcinogenic natural products for humans and livestock is well documented [23,24,25,26,27,28,29,30,31,32,35,36]. The potential PA contamination of food and feeding stuff has attracted recurrent attention. It is evident, that humans should not ingest food or herbal teas that contain PAs. However, some saturated PAs have interesting pharmacological and biological effects, e.g., spasmolytic, antihistaminic, anti-HIV and antiviral activities and as glucosidase inhibitor [233,234,235]. Solanecio angulatus and Crotalaria phillipsiae (PA containing plants from the families Asteraceae and Fabaceae) serve as sources of novel trypanocidal compounds [236]. The crude ethanol and hexane extracts of Heliotropium subulatum showed significant antiviral activity to Coxsackie, Poliomyelitis and Measles at 500 and 100 μg/mL, respectively, while heliotrine and 7-angeloylheliotrine demonstrated activity against Poliomyelitis and Vesicular stomatitis at concentration of 10 μg /mL [237]. PAs can inhibit the specific binding of radioligands to muscarinic acetylcholine and serotonin receptors and to a lesser degree to adrenergic receptors [20]. This neuromodulatory effect might be responsible for the avoidance of PA plants by many herbivores.

6. Chemotaxonomic Information of PAs in Boraginaceae

The distribution of PAs is documented in Table 1 and Table 2. A comparison of phytochemical occurrences of alkaloids with regard to recent results in the molecular phylogeny of the Boraginaceae was not intended in this review, but will be part of a separate publication. It has been shown previously that the occurrence of PAs in the plant kingdom does not necessarily mirror phylogenetic relatedness because the genes which encode the enzymes of alkaloid biosynthesis can be switched on or off [2,238].

6.1. Genus Amsinckia

PA profiles of twenty species and varieties of the genus Amsinckia have been investigated. All identified alkaloids were from retronecine, (+)- and (−)-supinidine, (+)-isoretrenocanol and trachelanthamidine types [42,43,44,46,104].

6.2. Genus Cynoglossum

Plants belongs to this genus contain alkaloids mainly derived from heliotridine type, in addition to (+)- and (−)-supinidine and trachelanthamidine bases [60,67,68,69,70,71,72,73,74,75,76,77,78,80,81,82,83,84,85,86,239].

6.3. Genus Echium

PAs of about 15 species from this genus have been investigated which accumulate PAs from retronecine type [11,28,29,60,87,89,90,91,92,93,96,99]. However, in earlier papers [47,97,98], the structure of major compounds in Echium vulgare were wrongly assigned to heliosupine and 3'-acetylheliosupine by means of paper chromatography and/or mass spectrometry. These compounds belong to heliotridine types. Recent publications revised the structures to the stereoisomeric analogue, echimidine and 3'-acetylechimidine (retronecine type), based on NMR and other advanced spectroscopic techniques [11,96,229].

6.4. Genus Heliotropium

Biosynthetic studies on necines that have been incorporated into PAs as well as the isolated and/or identified alkaloids in the genus Heliotropium indicated that it contains retronecine, (−)-trachelanthamidine, (−)-supindine, (−)-isoretronecanol, laburnine, lindelofidine, platynecine and subulacine nucleus, in addition heliotridine type PAs [28,29]. In addition to the isolation of the open-chained necines, a cyclic diester PA, e.g., helindicine has been recorded in H. indicum [130], incanine in H. olgae and trichodesmine in H. arguzioides [29].

6.5. Genus Paracaryum and Paracynoglossum

Only PAs from the heliotridine and (−)-trachelanthamidine type have been reported to be accumulated in these species [28,29,40,151].

6.6. Genus Rindera

All the previously examined Rindera species contain heliotridine–type PAs [120,152,169]. Echinatine is considered as a chemotaxonomical marker in this genus.

6.7. Genus Symphytum

Eleven Symphytum species (S. aintabicum, S. bohemium, S. consolidum, S. grandiflorum, S. ibericum, S. orientale, S. peregrinum, S. sylvaticum subsp. sepulcrale var. sepulcrale, S. tanaiense, S. tuberosum, S. × uplandicum) have been documented to synthesis pyrrolizidine alkaloids of retronecine type [17,29,170,177]. However, both retronecine and heliotridine type alkaloids were identified in S. asperum [171], S. caucasium [174], and S. officinale [29].

6.8. Other Boraginaceae Species

Species of genus Alkanna [40,41,184], Cryptantha [63,64,65,66], Mertensia [157], and Messerschmidia [158] produce only PAs of the retronecine type. Whereas Onosma heterophyllum and O. erecta [164] accumulate only heliotridine type PAs, other species of this genus synthesise retronecine type PAs [60,161,163,166,167] in addition to, supinidine [163] and trachelanthamidine type [167].

7. Conclusions

Our knowledge on PAs in Boraginaceae has improved substantially during the last decades, especially as advanced analytical methods, such as GLC, HPLC in combination with mass spectrometry have been widely applied. However, information on the biochemistry and physiology of PAs in plants and their function in plant insect interactions is still limited. More research has addressed pharmacological and toxicological properties of PAs in food plants and herbal medicines; public awareness is rightly concerned with PAs in food items and their place in the food chain. This review summarizes the state of our existing knowledge.

Acknowledgments

The authors thank Sameh Soliman and Ahmed El-Kadeem, Department of Pharmacognosy, Faculty of Pharmacy, Zagazig University for providing some published papers.

Author Contributions

This review was planned by both authors. Assem El-Shazly collected the information and drafted the manuscript which was interpreted and edited by Michael Wink. Both authors finally approved the published version.

Conflicts of Interest

Michael Wink is Editor-in-Chief of Diversity.

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