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

El-Shazly, Assem; Wink, Michael

doi:10.3390/d6020188

Open AccessReview

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

by

Assem El-Shazly

¹ and

Michael Wink

^2,*

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

Submission received: 6 February 2014 / Revised: 24 February 2014 / Accepted: 13 March 2014 / Published: 1 April 2014

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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

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 2. Necic acids occurring in pyrrolizidine alkaloids of Boraginaceae.

Table 1. List of plant species of the Boraginaceae containing PAs.

**Table 1.** List of plant species of the Boraginaceae containing PAs.
Species	Pyrrolizidine alkaloids	References
Alkanna orientalis	7-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 carinata	Echiumine, furcatine, 3'-acetylfurcatine, intermedine, 7-acetylintermedine, lycopsamine, myoscorpine, supinine.	[42]
A. douglasiana	Amabiline, cynaustrline, intermedine, lycopsamine, tessellatine, 9-(3'-acetylviridifloryl)turniforcidine.	[42,43]
A. eastwoodiae	Amabiline, intermedine, 3'-acetylintermedine, echiumine, lindelofine, lycopsamine, supinine, tessellatine.	[42]
A. furacata	Furcatine, intermedine, 3'-acetylfurcatine, lycopsamine, supinine, tessellatine.	[42]
A. grandiflora	Amabiline, intermedine, lycopsamine, 3'-aetyllycopsamine, 7-acetyllycopsamine, tessellatine, 9-acetyltessellatine.	[42]
A. hispida	Echiumine, intermedine, lycopsamine.	[44]
A. intermedia	Echiumine, intermedine, lycopsamine, sincamidine.	[44]
A. lunaris	Lycopsamine, 3'-acetyllycopamine, intermedine, supinine, tesslatine, 9'-acetyltessellatine.	[42]
A. lycopsoides	Amabiline, echiumine, intermedine, 3'-acetylintermedine, lycopsamine, supinine, tessellatine.	[42,44]
A. lycopsoides × menziesii var. intermedia	Amabiline, intermedine, 3'-acetylintermedine, lycopsamine, supinine, tessellatine.	[42]
A. menziesii	Intermedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine, 3',7-diacetyllycopsamine.	[45]
A. menziesii var. intermedia	Amabiline, 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. retrosa	Amabiline, intermedine, 3'-acetylintermedine, lycopsamine, myscorpine, 3'-acetylmyscorpine, supinine, tessellatine.	[42]
A. spectabilis var. microcarpa	Intermedine, 3'-acetylintermedine, lindelofine, lycopsamine, myscorpine, supinine, tessellatine.	[42]
A. specabtilis var. spectabilis	Intermedine, 3'-actylintermedine, lindelofine, lycopsamine, supinine.	[42]
A. spectabilis var. nicolai	Intermedine, lindelofine, lycopsamine, tessellatine, trachelanthamine, supinine.	[42]
A. tessellata	Intermedine, lycopsamine, 3'-acetylintermedine, 3'-acetyllycopsamine, 7-acetylintermedine, 7-acetyllycopsamine, 3',7-diacetylintermedine, 3'-7-diacetyllycopsamine.	[46]
A. tessellata var. gloriosa	Amabiline, intermedine, lycopsamine, supinine, tessellatine, tracelanthamine, viridiflorine, 3'-acetylviridiflorine.	[42,43]
A. tessellata var. tessellata	Amabiline, intermedine, lycopsamine, 3'-acetyllycopsamine, tessellatine, 3'-acetyltessellatine, 9-acetyltessellatine, 9,3'-acetyltessellatine, 9-(3'-acetylviridifloryl)-turniforcidine.	[42]
A. vernicosa	Furcatine, 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. milleri	Heliotridine, 7-angeloylheliotridine, rinderine, retronecine, supinine, viridiflorine, 9-curassavoyleliotridine, 7-acetyl-9-curassavoylheliotridine.	[40]
A. officinalis	Intermedine, curassavine, lycopsamine, 7-aceyllycopsamine.	[47,48,49]
A. strigosa	Heliotridine 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 decumbens	7-angeloylrtronecine, 9-angeloylretronecine, 7-tigloylrtronecine, 9-tigloylretronecine, europine, heliotrine, lycopsamine, rinderine, supinine.	[52]
Arnebia euchroma	7-angeloylrtronecine, 9-angeloylretronecine	[53]
A. hispidissima	Echimidine, monocrotaline.	[54]
Asperugo procumbens	Amabiline (or supinine), echinatine.	[47]
Borago officinalis	Amabiline, intermedine, 7-acetylintermedine, lycopsamine, 7-acetyllycopsamine, supinine, thesinine, thesinine-4'- O-β-D-glucoside.	[55,56]
Caccinia crassifolia	Supinine, Heliotridine or retronecine trachelanthate.	[57]
C. glauca	Retronecine 7:9 -dibenzoate.	[58]
Cerinthe glabra	Lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine, 3',7-diacetyllycopsamine, supinine, 7-hydroxymethyl butyryl-9-viridifloryl-retronecine (or isomer).	[59]
Cerinthe minor	Intermedine, 7-angeloylretronecine, 9-angeloyl-7-viridiflorylretronecine, lycopsamine.	[60,61]
Cordia myxa	macrophylline	[62]
C. sinensis	floridanine	[62]
Cryptantha cana	Intermdine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine.	[63]
C. clevelandii	Intermdine, 3'-acetylintermedine, echiumine, 2'',3''-epoxyechiumine, thero-2',3' dihydroxyechiumine, erytho-3''-chloro-2''-hydroxyechiumine.	[63]
C. confertiflora	Amabiline, intermedine, lycopsamine, tessellatine, 9-acetyltessellatine.	[63]
C. crassipes	Lycopsamine, intermedine and their 3'-acetyllycopsamine, 3'-acetylintermedine, 7-acetyllycopsamine, 7-acetylintermedine, amabiline, echiumine, dihydroechumine, echimiplatine, lepanthine.	[64]
C. fendleri	7-Angeloylretronecine, 9-angeloylretronecine, latifoline, neolatifoline.	[63]
C. flava	Intermedine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine.	[63]
C. inequata	Echimidine, acetylechimidine, echiuplatine, methylechiuplatine, lycopsamine, intermedine, dihydroxyechiumine.	[65]
C. jamesii	Intermedine, lycopsamine, 3'- acetyllycopsamine, 7-aetyllyopsamine.	[66]
C. leiocarpa	7-Angeloylretronecine, 9-angeloylretronecine, echiumine, intermedine, 3'-acetylintermedine, 2'',3''-epoxyechiumine, thero-2',3'-dihydroxyechiumine, erytho-3''-chloro-2''-hydroxyechiumine	[63]
C. thyrsiflora	Intermedine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine	[63]
C. utahensis	Cryptanthine	[65]
C. virgata	Intermedine, 3'-acetylintermedine, 7-acetylintemedine, lycopsamine, 3'-acetyllycopsamine, 7-acetyllycopsamine	[63]
C. virginiensis	Amabiline, intermedine, lycopsamine, tessellatine.	[63]
Cynoglossum amabile	Amabiline, echinatine, 7-acetylechinatine, lycopsamine, rinderine, supinine. 9-angeloylretronecine, 9-angeloyl-7-viridiflorylretronecine,	[60,67,68]
C. australe	Cynausine, cynaustraline.	[68]
C. clandestinum	9-Angeloyl-7-viridiflorylretronecine, trachelanhamine	[60]
C. columnae	N-oxides of echintine, rinderine, 3’-acetylrinderine, 7-tigloyl-9-(2-deoxy-2-methyl)echimidinyl heliotridine.	[69]
C. creticum	Cynoglossamine, 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. germanicum	Echinatine, viridiflorine.	[77]
C. glochidiatum	Amabiline	[78]
C. lanceolatum	Cynaustine, cynaustraline.	[78]
C. latifolium	7-Angeloylheliotridine, latifoline.	[79]
C. macrostylum	Echinatine, heliosupine.	[80]
C. montanum	Cynaustine, cynaustraline, echinatine, heliosupine.	[81]
C. nervosum	Heliotrine, echinatine, rinderine and their N-oxides.	[82]
C. officinale	Echinatine, 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. pictum	Echinatine, heliosupine, pictumine.	[85]
C. viridiforum	Heliosupine, viridiflorine.	[86]
Echium amoenum	Echimidine, echimidine isomer (tigloyl), 7-angeloylretronecine, 7-tigloylretronecine.	[87]
E. angustifolium	Echimidine	[88]
E. diffusum	Heliotridine or retronecine esters.	[28]
E. glomeratum	7-Angeloylretronecine, 9-angeloylretronecine, (7S,8R)petranine, (7S,8S)petranine.	[89]
E. horridum	Echimidine, 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. humile	Echimidine, 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. hypertropicum	Echimidine, echihumiline, 7-(2-methylbutyryl)-9-echimidinylretronecine, 7-senecioylretronecine, 9-angeloylretronecine, lycopsamine, 7-acetyl-lycopsamine	[92]
E. italicum	Echimidine	[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. pininana	Echimidine, ehiupinine, 3'-aetylintermedine, hydroxymyoscorpine, myoscorpine.	[95]
E. rauwolfii	Echimidine, 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. sericeum	Echimidine, symlandine (or symphytine).	[54]
E. setosum	Echimidine, 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. simplex	7-Angeloylretronecine, 9-angeloylretronecine.	[61]
E. stenosiphon Webb subsp. stenosiphon	Echimidine, 7-(2-methylbutyryl)-9-echimidinylretronecine	[92]
E. tuberculatum	Echimidine,7-angeloyl-9-viridiflorylretronecine, 7-viridiflorylretronecine.	[60]
E. vulgare	Asperumine, 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. wildpretti	Echimidine and its N-oxide.	[99]
Ehretia aspera	Ehretinine	[100]
Eritrichium rupestre	7-Angeloylretronecine, 7-angeloyl-9-viridiflorylretronecine, 7-viridiflorylretronecine	[60]
Hackelia californica	Hackelidine, longitubine, 7-acetylhackelidine, 9-latifolylretronecine, 7-acetyl-9-latifolylretronecine	[101,102]
H. floribunda	Latifoline and its N-oxide.	[103]
H. longituba	Latifoline, neolatifoline, longitubine, 7-angeloylretronecie, 9-angeloylretronecine.	[104]
Heliotropium acutifolium	Heliotrine	[105]
H. amplexicaule	Indicine	[29]
H. angiospermum	Subulacine, lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. arbainense	Europine, heliotrine, lasiocarpine.	[71]
H. arborescens (=H. peruvianum)	Indicine, 3'-acetylindicine, lasiocarpine.	[107]
H. arguzioides	Heliotrine, trichodesmine.	[28]
H. bacciferum	Europine, heliotrine, heleurine and their N-oxides, supinine.	[108,109]
H. bovei	Europine, 7-acetyleuropine, lasiocarpine, 5'-acetyllasiocarpine, lasiocarpine N-oxide, 5'-acetyllasiocarpine N-oxide.	[110]
H. bracteatum	Helibractinecine, retronecine, helibracteatinine, helibracteatine	[111,112]
H. bursiferum	7-Angeloylretronecine.	[113]
H. circinatum	7-angeloylheliotrine, echinatine, europine, heleurine, heliotrine, lasiocarpine.	[114]
H. confertifolium	lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. crassifolium	Ilamine, europine and their N-oxides.	[115]
H. curassavicum	Coromandaline, coromandalinine, curassavine, curassavinine, curassanecine, heliocurassavine, heliocurassavinine, heliocurassavicine, heliocoromandaline, heliovicine, 7-angeloylheliotridine, trachelanhamidine, retronecine, supinidine.	[106,116,117,118]
H. curassavicum var. argentium	9-(3'-isovaleryl) viridifloryl retronecine, 9-(3'-acetyl) viridifloryl retronecine.	[119]
H. curassavicum var. curassavicum	9-(3'-isovaleryl) viridifloryl retronecine, 9-(3'-acetyl) viridifloryl retronecine.	[119]
H. dasycarpum	heliotrine	[120]
H. digynum (H. luteum)	Europine, heliotrine, 7-angeloylheliotrine, lasiocarpine.	[121]
H. disciforme	Heliotrine, 2'-actylheliotrine, heliotrine N-oxide, heleurine, heliorine N-oxide.	[122]
H. dissitiflorum	Heliotrine, heliotrine N-oxide, europine, 5'-deoxylasiocarpine.	[123]
H. eichwaldii	Heliotrine, 7-angeloylheliotrine, lasiocarpine.	[124]
H. esfandiarii	Europine, europine N-oxide.	[125]
H. europaeum	Europine, acetyleuropine, heleurine, heliotrine, 7-angeloylheliotrine, lasiocarpine, 6-acetyllasiocarpine, heliotrine N-oxide, dehydroheliotrine, 5'-acetyllasiocarpine N-oxide, N-(dihydropyrrolizinomethyl)-heliotrine, supinine.	[126,127]
H. floridum	Floridine, floridinine, floridimine, heliovicine, 3'-acetyltrachelanthamine.	[128]
H. foliosisimum	lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. fruticosum	lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. hirsutissimum	Europine, heliotrine, heleurine, lasiocarpine, 3'-acetyllasiocarpine, 5'-acetyllasiocarpine, supinine, N-oxides of acetylasiocarpine, 3'-acetyleheliosupine.	[29,129]
H. indicum	Echinatine, helindicine, heliotrine, heleurine, indicine, acetylindicine, indicinine, lasiocarpine, lycopsamine, rinderine, supinine, lindelofidine, retronecine, supinidine, trachelanthamine.	[106,116,130,131,132]
H. keralense	Intermedine, isolycopsamine, retronesine.	[133]
H. lasiocarpum	Heliotrine, lasiocarpine.	[29]
H. marifolium	Europine, heliotrine, indicine, lasiocarpine.	[29]
H. maris mortui	Europine, lasiocarpine.	[29,71]
H. megalanthum	Lycopsamine, megalanthonine.	[134]
H. molle	subulacine	[29]
H. olgae	Heliotrine, incanine.	[135]
H. ovalifolium	Heliofoline, retronecine.	[136]
H. peruvianum	Rinderine	[29]
H. popovii subsp. gillianum	Heliotrine	[28]
H. procumbens	Lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. queretaroanum	Lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. racemosum	Lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. ramosissimum	Heliotrine	[28]
H. rotundifolium	Europine, 5'-acetyleuropine, heliotrine, lasiocarpine.	[137,138]
H. scabrum	Heliscabine, retronecine.	[139]
H. sessei	Lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
H. spathulatum	Amabiline, coromandaline, coromandalinine, heliovicine, curassavinine, curassavine, heliospathine, heliospathuline, lindelofidine, retronecine, supinidine, trachelanthamidine.	[116,140]
H. steudneri	Lycopsamine	[27]
H. strigosum	Strigosine, trachelanthamidine	[25,141]
H. suaveolens	Echinatine, europine, heliotrine, lasiocarpine.	[29]
H. subulatum	Subulacine; retronecine, heliotrine, 7-angeloylheliotridine	[142]
H. supinum	Echinatine, heliosupine, heliotrine, 7-angeloylheliotridine (and its trachelanthic and viridifloric esters), lasiocarpine, supinine.	[27,143]
H. ternatum	subulacine	[27]
H. transalpinum	Intermedine, indicine, lycopsamine, rinderine, 3'-acetylrinderine, supinine.	[144]
H. transalpinum var. transalpinum	Transalpinecine, subulacine.	[145]
H. transoxanum	Heliotrine	[105]
H. wigginsii	Lindelofidine, retronecine, supinidine, trachelanthamidine.	[106]
Lappula glochidiata	Echinatine	[146]
L. intermedia (Echinospermum intermedium)	Lasiocarpine	[147]
L. myosotis	Intermedine, lycopsamine , 7-acetylintermedine, 7-acetyllycopsamine.	[35,148]
L. spinocarpos	Amabiline, intermedine, 7-angeloylheiotridine, 9- heliotrinoylretronecine, lycopsamine, 7-acetyllycopsamine, retronecine, trachelanthamine, supinine, viridiflorine.	[40]
Lindelofia anchusoides (L. macrostyla)	Lindelofamine, lindelofine.	[28]
L. angustifolia	Amabiline, echinatine	[78]
L. longiflora	Echinatine and its N-oxide.	[149]
L. olgae	Viridiflorine	[150]
L. pterocarpa	Viridiflorine	[151]
L. spectabilis	Echinatine, 3'-acetylechinatine, monocorotaline.	[124]
L. stylosa	Echinatine, lindelofine, viridiflorine.	[135]
L. tschimganica	Echinatine, carategine, viridiflorine.	[152]
Lithospermum canesens	Canesine, canescenine, 3'-acetycanesine, 3'-acetylcanescenine, lycopsamine, 7-acetyllycopsamine, 7-acetylintermedine.	[153,154]
L. erythrorhizon	Intermedine, myoscorpine, hydroxymyoscorpine.	[155]
L. officinale	Lithosenine, acetyllithosenine.	[156]
L. purpureocoeruleum	Lycopsamine	[60]
Macrotomia echioides	Macrotomine	[28]
Mertensia bakeri	Lycopsamine	[157]
M. ciliata	Intermedine, lycopsamine.	[157]
Messerschmidia argentea	Indicine, 3'-acetylindicine, and their N-oxide.	[158]
M. sibirica	Lycopsamine, 9-angeloylretronecine.	[28]
Moltikiopsis ciliata (Lithospermum callosum)	Echinatine, heliotrine.	[108]
Myosotis scorpioides (=M. palustris)	Myoscorpine, symphytine, scorpioidine, 7-acetylscorpioidine.	[159]
M. sylvatica	Heliosupine, 3'-acetylheliosupine, 9-angeloylretronecine, trachelanthamine.	[25]
Neatostema apulum	Amabiline, lycopsamine and their N-oxides.	[160]
Nonnea lutea	7-viridiflorylretronecine	[60]
N. setosa	7-viridiflorylretronecine	[60]
Omphalodes verna	Isoretronocanol or its isomer.	[27]
Onosma alborosea	Intermedine, lycopsamine, 7-acetylintermedine, 7-acetylycopsamine.	[161]
O. alboroseum × sanguinolentum	9-Angeloylretronecine, echimidine, lycopsamine, intermedine, 7-acetylintermedine, 7-acetylycopsamine.	[161,162]
O. arenaria	7-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. pennina	Intermedine, lycopsamine, 7-acetylintermedine, 7-acetylycopsamine.	[161]
O. erecta	N-oxides of 7-O-acetylechinatine, viridinatine, stereoisomer, 7-epi-echimiplatine, onosmerectine.	[164]
O. hetrophyllum	Helioridine, 1-methylene-8α-pyrrolizidine.	[165]
O. leptantha	Echihumiline, 3’-acetylechihumiline, leptanthine and their N-oxides.	[166]
O. stellulatum	Echimidine, 7-viridiflorylretronecine, heliospathuline, leptanthine, lyopsamine and heir N-oxides, 7-acetylintermedine, dihydroechinatine, trahelanthamine, uplandicine.	[60,167]
Paracaryum himalayense	Viridiflorine	[151]
P. intermedium	7-Angeloylheliotridine, 7-senecioylheliotridine, rinderine, 7-angeloylrindrine, 7-senecioylrinderine, viridiflorine.	[40]
P. regulosum	Echinatine, heliosupine, 7-angeloylheliotridine, rinderine, viridiflorine.	[40]
Paracynoglossum imeretinum	Echinatine, heliosupine.	[29]
Pulmonaria obscura	Intermedine, lycopsamine, 7-acetylintermedine, 7-acetylycopsamine.	[168]
Rindera austroechinata	Echinatine, rinderine, 7-angeloylheliotridine	[57,152]
R. baldschuanica	Echinatine, rinderine, trachelanthamine, turkestanine	[152]
R. cyclodonta	Echinatine	[120]
R. echinata	Echinatine, trachelanthamine	[120]
R. oblongifolia	Cerategine, echinatine, turkestanine.	[152]
R. umbellata	7-Angeloyl-9-(+)-trachelanthyl heliotridine, lindelofine, punctanecine, 7-angeloyl heliotridane, 7-angeloyl heliotridine, heliosupine, 9-(+)-trachelanthyl-laburnine, echinatine.	[169]
Solenanthus circinnatus	Echinatine	[151]
S. coronatus	Echinatine	[135]
S. karateginus	Cerategine, ehinatine.	[151]
S. turkestanicus	Rinderine, turkestanine.	[135,150]
Symphytum aintabicum	Echimidine	[170]
S. asperum	Echimidine, symphytine, asperumine, ehinatine, heliosupine, acetylechimidine (or its isomer), aetyllyopsamine (or its isomer), symviridine	[171,172]
S. bohemium	Echimidine, lycopsamine, 7-acetyllycopsamine, symphytine.	[173]
S. caucasium	Asperumine, echimidine, echinatine, heliotrine, lasiocarpine.	[174]
S. consolidum	Echimidine, symphytine.	[175]
S. grandiflorum	Echimidine, lycopsamine, symphytine.	[176]
S. ibericum	Echimidine, lycopsamine, symphytine.	[176]
S. officinale	Lycopsamine, 7-acetyllycopsamine, symphytine, echimidine, echinatine, heliosupine, intermedine, 7-acetylintermedine, viridiflorine, symviridine.	[17,162,171,172,177,178,179]
S. orientale	Anadoline, echimidine, symphytine.	[28]
S. peregrinum	Intermedine, 7-acetylintermedine, lycopsamine, 7-acetyllycopsamine, symphytine.	[27]
S. sylvaticum subsp. sepulcrale var. sepulcrale	Echimidine N-oxide	[170]
S. tanaiense	Echimidine, lycopsamine, 7-acetyllycopsamine, symphytine.	[173]
S. tuberosum	7-Angeloylretronecine; anadoline, echimidine, lycopsamine, 7-acetyllycopsamine, symphytine.	[28,162,176]
S × uplandicum	Echimidine, intermedine, 7-acetylintermedine lycopsamine, 7-acetyllycopsamine, symphytine, symlandine, symviridine, uplandicine.	[172,180]
Tournefortia sarmentosa	Supinine	[28]
T. sibirica	Turneforcine	[29]
T. sogdiana	Echinatine	[57]
Trahlenthus hissaricus	Trachelanthine, trachelanthamine, viridiforine.	[29]
T. korolkovii	Trachelanthine, trachelanthamidine, trachelanthamine.	[57,150]
Trichodesma africanum	Europine, intermedine, lycopsamine, trichodesmine, retronecine, viridiflorine	[40,71,181]
T. ehrenbergii	Senkirkine, supinine.	[54]
T. incanum	Inanine, trihodesmine.	[46]
T. zeylanicum	Supinine	[182]
Ulugbekia tschimganica	Uluganine	[183]

Table 2. Alkaloid composition of investigated species of Boraginaceae.

**Table 2.** Alkaloid composition of investigated species of Boraginaceae.
Compounds	Sources	References
3'-Acetylcanesine	Lithospermum canesens	[153,154]
3'-Acetylcanescenine	Lithospermum canesens	[153,154]
7-Acetyl-9-curassavoylheliotridine	Anchusa milleri	[40]
7-Acetyl-9-(2,3-dihydroxybutryl) retronecine	Onosma arenaria	[163]
7-Acetyl-9-(2-dimethylbutryl) retronecine	Onosma arenaria	[163]
3'-Acetylechinatine	Cynoglossum creticum	[70]
	Cynoglossum officinale	[67]
	Lindelofia spectabilis	[124]
	Messerschmidia argentea	[158]
7-Acetylechinatine	Cynoglossum amabile	[67]
	Cynoglossum officinale	[67,84]
	Onosma erecta	[69]
3'- Acetylechihumiline	Onosma leptantha	[166]
3'-Acetylechiumine	Amsinckia menziessi var. intermedia	[42]
3'-Acetylechiumine	Cryptantha clevelandii	[63]
3'-Acetylechimidine	Echium vulgare	[96]
5'-Acetylechimidine	Echium vulgare	[11]
5'-Acetyleuropine	Heliotropium disciforme	[122]
5'-Acetyleuropine	Heliotropium rotundifloium	[138]
7-Acetyleuropine	Heliotropium bovi	[110]
3'-Acetylfurcatine	Amsinckia carinata	[42]
3'-Acetylfurcatine	Amsinckia furacata	[42]
3'-Acetylheliosupine	Cynoglossum creticum	[70]
	Cynoglossum officinale	[67,83]
	Heliotropium hirsutissimum	[129]
7-Acetyl-9-(2-hydroxy-3-methylbutryl) retronecine	Onosma arenaria	[163]
3'-Acetylindicine	Heliotropium arborescens (H. peruvianum)	[28]
3'-Acetylindicine	Messerschmidia argentea	[158]
3'-Acetylintermedine	Amsinckia 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-Acetylintermedine	Amsinckia 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'-Acetyllasiocarpine	Heliotropium hirsutissimum	[129]
7-Acetyl-9-latifolylretronecine	Hackelia californica	[101]
3'-Acetyllithosenine	Lithospermum officinale	[156]
3'-Acetyllycopsamine	Amsinckia 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-Acetyllycopsamine	Amsinckia 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) retronecine	Onosma arenaria	[163]
3'-Acetylmyscorpine	Amsinckia menziesii var. intermedia	[42]
3'-Acetylmyscorpine	Amsinckia retrosa	[42]
7-Acetylretronecine	Onosma arenaria	[163]
3'-Acetylrinderine	Cynoglossum columnae	[69]
3'-Acetylrinderine	Heliotropium transplinum	[144]
7-Acetyl-9-sarracinoyl retronecine	Alkanna tinctoria	[40]
7-Acetylscorpioidine	Myosotis scorpioides	[159]
3'-Acetylsupinine	Onosma arenaria	[163]
3'-Acetyltessellatine	Amsinckia tessellata var. tessellata	[42]
9-Acetytessellatine	Amsinckia grandifkora	[42]
	Amsinckia lunaris	[42]
	Amsinckia tessellata var. tessellata	[42]
3'-Acetyltrachelanthamine	Heliotropium floridum	[128]
9-Acetyltrachelanthamine	Anchusa arvensis	[40]
3'-Acetylviridiflorine	Amsinckia tessellata var. gloriosa	[42]
9-(3'-Acetyl)viridiflory retronecine	Heliotropium curassavicum var. argentinum	[119]
9-(3'-Acetyl)viridiflory retronecine	Heliotropium curassavicum var. curassavicum	[119]
9-(3'-Acetylviridifloryl) turniforcidine	A. douglasiana	[42]
9-(3'-Acetylviridifloryl) turniforcidine	A. tessellata var. tessellata	[42]
7-Acetylvulgarine	Echium vulgare	[11]
Amabiline	Amsinckia 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]
Anadoline	Symphytum orientale	[28]
Anadoline	Symphytum tuberosum	[28]
7α-Angeloyl-1-chloromethy-1,2-dihydropyrrolizidine	Cynoglossum creticum	[70]
7-Angeloyl-9-(2,3-dihydroxybutyryl)heliotridine	Cynoglossum officinale	[67]
7-Angeloyl-9-(2,3-dihydroxybutyryl)retronecine	Echium horridum	[90]
	Echium rauwolfii	[90]
	Echium setosum	[96]
	Onosma arenaria	[163]
7-Angeloyl-9-(2,3-dihydroxypropanoyl)retronecine	Alkanna orientalis	[40]
7-Angeloyl-9-(2,3-dihydroxypropanoyl)retronecine	Alkanna tinctoria	[40]
7-Angeloyl-1-formyl-6,7-dihydro-5H-pyrrolizidine	Cynoglossum officinale	[67]
7-Angeloyl-9-(hydroxypropenoyl)retronecine	Alkanna orientalis	[40]
7-Angeloyl-9-(hydroxypropenoyl)retronecine	Alkanna tinctoria	[40]
7-Angeloylechinatine	Cynoglossum officinale	[67]
7-Angeloylheliotridine	Anchusa 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-Angeloylheliotridine	Paracaryum intermedium	[40]
	Paracaryum regulosum	[40]
	Rindera austroechinata	[57]
7-Angeloylheliotrine	Heliotropium circinatum	[114]
	Heliotropium digynum (H. luteum)	[121]
	Heliotropium eichwaldii	[124]
	Heliotropium europaeum	[127]
	Rindera umbellata	[169]
7-Angeloyllycopsamine	Echium horridum	[90]
7-Angeloyllycopsamine	Echium rauwolfii	[90]
7-Angeloyl-9-(2-methylbutyryl)heliotridine	Cynoglossum creticum	[70]
7-Angeloyl-9-(2-methylbutyryl)heliotridine	Cynoglossum offocinale	[67]
7-Angeloyl-9-(2-methylbutyryl)retronecine	Echium horridum	[90]
7-Angeloyl-9-(2-methylbutyryl)retronecine	Echium rauwolfii	[90]
7-Angeloylretronecine	Alkanna 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-Angeloylretronecine	Alkanna 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-Angeloylrinderine	Cynoglossun officinale	[67]
9-Angeloyltrachelanthamidine	Anchusa arvensis	[40]
7-Angeloyl-9-(+)-trachelanthylheliotridine	Rindera umbellata	[169]
9-Angeloyl-7-viridiflorylretronecine	Cerinthe minor	[60]
	Cynoglossum amabile	[60]
	Cynoglossum clandestinum	[60]
	Echium tuberculatum	[60]
	Eritrichium rupestre	[60]
Asperumine	Echium vulgare	[98]
	Symphytum asperum	[172]
	Symphytum caucasium	[174]
9-(Butyryl-2-ene) supinidine	Onosma arenaria	[163]
Canescine	Lithospermum canescens	[153,154]
Canescenine	Lithospermum canescens	[153,154]
Carategine	Lindelofia tschimganica	[27]
	Rindera oblongifolia	[152]
	Solanthus karateginus	[151]
Coromandaline	Heliotropium curassavicum	[117,118]
Coromandaline	Heliotropium spathulatum	[140]
Coromandalinine	Heliotropium curassavicum	[117]
Coromandalinine	Heliotropium spathulatum	[140]
Cryptanthine	Cryptantha utahensis	[65]
Curassanecine	Heliotropium curassavicum	[117]
Curassavine	Anchusa officinalis	[49]
	Heliotropium curassavicum	[117]
	Heliotropium spathulatum	[140]
Curassavinine	Heliotropium curassavicum	[117]
Curassavinine	Heliotropium spathulatum	[140]
9-Curassavorylheliotridine	Anchusa milleri	[40]
Cynaustrine	Cynoglossum australe	[68]
	Cynoglossum lanceolatum	[78]
	Cynoglossum montanum	[81]
Cynaustraline	Amsinckia douglasiana	[42]
	Cynoglossum australe	[68]
	Cynoglossum furcatum	[73]
	Cynoglossum lanceolatum	[78]
	Cynoglossum montanum	[81]
Cynoglossamine	Cynoglossum creticum	[72]
Dehydroheliotrine	Heliotropium europaeum	[185]
5-Deoxylasiocarpine	Heliotropium dissitiflorum	[123]
3',7-Diacetylintermedine	Amsinckia menziesii var. intermedia	[42]
	Amsinckia tessellata	[46]
	Anchusa arvensis	[40]
3',7-Diacetyllycopsamine	Amsinckia menziesii	[45]
3',7-Diacetyllycopsamine	Amsinckia tessellata	[46]
3',7-Diacetyllycopsamine	Anchusa arvensis	[40]
3',7-Diacetyllycopsamine	Cerinthe glabra	[59]
3',9-Diacetyltessellatine	Amsinckia tessellata var. tessellata	[42]
5,6-Dihydro-7,9-dimethoxy-7H-pyrrolizine	Onosma arenaria	[163]
Dihydroechinatine	Onosma stellulatum	[167]
thero-2'',3''-Dihydroxyechiumine	Cryptantha clevelandiiCryptantha inequata	[63,65]
thero-2'',3''-Dihydroxyechiumine	Cryptantha leiocarpa	[63]
Dihydroxytriangularine	Alkanna orientalis	[40,41]
Dihydroxytriangularine	Alkanna tinctoria	[40,41]
Dihydroxytriangularicine	Alkanna orientalis	[40]
Dihydroxytriangularicine	Alkanna tinctoria	[40]
Echihumiline	Echium hypertropicum	[92]
	Echium humile	[91]
	Echium vulgare	[96]
	Onosma leptantha	[166]
Echimidine	Arnebia 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]
Echimidine isomer (tigloyl)	Echium horridum	[90]
Echimidine isomer (tigloyl)	Echium rauwolfii	[90]
	Echium setosum	[96]
	Echium vulgare	[96]
Echimiplatine	Cryptantha crassipes	[64]
	Echium plantagineum	[93]
	Echium vulgare	[11]
Echinatine	Asperugo 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]
Echiumine	Amsinckia 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]
Echiupine	Echium pininana	[95]
Echiuplatine	Cryptantha inequata	[65]
	Echium plantagineum	[93]
	Echium vulgare	[11]
Echivulgarine	Echium vulgare	[11]
Ehretinine	Ehretia aspera	[100]
2'',3''-Epoxyechiumine	Cryptantha clevelandii	[63]
2'',3''-Epoxyechiumine	Cryptantha leiocarpa	[63]
Erythro-2'',3''-chloro-2''-hydroxyechiumine	Cryptantha clevelandii	[63]
Erythro-2'',3''-chloro-2''-hydroxyechiumine	Cryptantha leiocarpa	[63]
7-Epi-echimiplatine	Onosma erecta	[69]
1α-2α-Epoxy-1β-hydroxymethyl-8α-pyrrolizidine	Heliotropium transalpinum var. transalpinum	[145]
Europine	Heliotropium arbainense	[71]
	Heliotropium bacciferum	[108,109]
	Heliotropium bovi	[110]
	Heliotropium circinatum	[114]
	Heliotropium crassifolium	[115]
	Heliotropium digynum (H.luteum)	[121]
	Heliotropium dissitiflorum	[123]
	Heliotropium esfandiarii	[125]
	Heliotropium europaeum	[126,127,186]
	Heliotropium hirsutissinum	[129]
	Heliotropium marifolium	[29]
	Heliotropium maris mortui	[71]
	Heliotropium rotundifolium	[137,138]
Floridanine	Cordia sinensis	[62]
Floridimine	Heliotropium floridum	[128]
Floridine	Heliotropium floridum	[128]
Floridinine	Heliotropium floridum	[128]
Furcatine	Amsinckia carinata	[42]
	Amsinckia furacata	[42]
	Amsinckia vernicosa	[42]
Hackelidine	Hackelia californica	[102]
Heleurine	Heliotropium bacciferum	[109]
	Heliotropium circinatum	[114]
	Heliotropium disciforme	[122]
	Heliotropium europaeum	[126,127,186]
	Heliotropium hirsutissimum	[129]
	Heliotropium indicum	[131]
Helibracteatine	Heliotropium bracteatum	[112]
Helibractinecine	Heliotropium bracteatum	[111]
Helibracteatinecine	Heliotropium bracteatum	[112]
Helibracteatinine	Heliotropium bracteatum	[112]
Heliofoline	Heliotropium ovalifolium	[136]
Helindicine	Heliotropium indicum	[130]
Heliocoromandaline	Heliotropium curassavicum	[117]
Heliocurassavine	Heliotropium curassavicum	[117]
Heliocurassavicine	Heliotropium curassavicum	[117]
Heliocurassavinine	Heliotropium curassavicum	[117]
Heliospathine	Heliotropium spathulatum	[140]
Heliospathuline	Heliotropium spathulatum	[140]
Heliospathuline	Onosma stellulatum	[167]
Heliosupine	Cynoglossium 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]
Heliotridine	Anchusa milleri	[90]
Heliotridine	Onosma heterophyllum	[165]
Heliotridine 2S-hydroxy-2S(1S-hydroxyethyl0-4-methyl-pentanoyl ester	Anchusa strigosa	[50]
Heliotrine	Arenbia decumbens	[52]
	Cynoglossum nervosum	[82]
	Heliotropium acutifolium	[105]
	H. arbainense	[71]
	H. bacciferum	[108,109]
	Heliotropium circinatum	[114]
	Heliotropium dasycarpum	[120]
	Heliotropium digynum	[121]
	Heliotropium disciforme	[122]
	Heliotropium dissitiflorum	[123]
	Heliotropium eichwaldii	[124]
	Heliotropium europaeum	[127,185,186]
	Heliotropium hirsutissimum	[129]
	Heliotropium indicum	[130,131]
	Heliotropium lasiocarpum	[29]
Heliotrine	Heliotropium 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]
Heliovicine	Heliotropium spathulatum	[140]
Heliscabine	Heliotropium scabrum	[139]
Hydroxymyoscorpine	Echium pininana	[95]
Ilamine	Heliotropium crassifolium	[115]
Incanine	Heliotropium olgae	[29]
Incanine	Trichodesma incanum	[46]
Indicine	Heliotropium amplexicaule	[29]
	Heliotropium arborescens (H. pruvianum)	[107]
	Heliotropium indicum	[130,131]
	Heliotropium marifolium	[29]
	Heliotropium transalpinum	[144]
	Messerschmidia argentea	[158]
Indicinine	Heliotropium indicum	[130,131]
Isoechinatine	Cynoglossum furcatum (C. zeylanicum)	[75]
Isolycopsamine	Heliotropium keralense	[190]
Isoretronocanol (or its isomer)	Omphalodes verna	[27]
9-(3'-Isovaleryl)viridiflory retronecine	Heliotropium curassavicum var. argentinum	[119]
9-(3'-Isovaleryl)viridiflory retronecine	Heliotropium curassavicum var. curassavicum	[119]
Intermedine	Amsinckia 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]
Intermedine	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]
	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]
Lactodine	Cynoglossum furcatum	[76,187]
Lasiocarpine	Heliotropium 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]
Latifoline	Cryptantha fendleri	[63]
	Cynoglossum latifolium	[79]
	Hackelia californica	[101]
	Hackelia floribunda	[103]
	Hackelia longituba	[104]
	Lindelofia stylosa	[27]
9-Latifolylretronecine	Hackelia californica	[101]
Leptanthine	Cryptantha 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]
Lindelofamine	Lindelofia anchusoides (L. macrostyle)	[28]
Lindelofidine	Heliotropium 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]
Lithosenine	Lithospermum officinale	[156]
Longitubine	Hackelia californica	[101]
Longitubine	Hackelia logituba	[104]
Lycopsamine	Amsinckia 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]
Macrophylline	Cordia myxa	[62]
Macrotamine	Macrotomia echioides	[28]
Megalanthonine	Heliotropium megalanthum	[134]
Methyechiuplatine	Cryptantha inequata	[65]
1-Methylene-8α-pyrrolizidine	Onosma heterophyllum	[165]
7-(2-Methylbutyryl)retronecine	Echium humile	[91]
7-(2-Methylbutyryl)retronecine	Echium vulgare	[96]
9-(2-Methylbutyryl)retronecine	Echium vulgare	[96]
7-(2-Methylbutyryl)-9-(2,3-dihydroxybutyryl)retronecine	Echium humile	[91]
7-(2-Methylbutyryl)-9-(2,3-dihydroxybutyryl)retronecine	Echium vulgare	[96]
7-(2-Methylbutyryl)-9-echimidinyl retronecine	Echium humile	[91]
	Echium hypertropicum	[92]
	Echium stenosiphon subsp. stenosiphon	[92]
	Echium vulgare	[96]
Monocrotaline	Arnebia hispidissima	[54]
Monocrotaline	Lindelofia spectabilis	[124]
Myoscorpine	Amsinckia carinata	[42]
	Amsinckia menziesii var. intermedia	[42]
	Amsinckia retrosa	[42]
	Amsinckia spectabilis var. microcarpa	[42]
	Echium pininana	[95]
	Linelfolia erythrorhizon	[155]
	Myosotis scorpioides	[159]
Neocoromandaline	Cynoglossum furcatum	[74]
Neolatifoline	Cryptantha fendleri	[63]
Neolatifoline	Hackelia logituba	[104]
Onosmerectine	Onosma erecta	[69]
(7S,8R)Petranine	Echium glomeratum	[89]
(7S,8S)Petranine	Echium glomeratum	[89]
Pictumine	Cynoglossum pictum	[28]
Platynecine	Cryptantha leiocarpa	[63]
Platynecine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl ester	Anchusa strigosa	[50,51]
Punctanecine	Rindera umbellata	[169]
Pycnanthine	Echium humile	[91]
Retronecine	Anchusa 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- dibenzoate	Caccinea glauca	[58]
Retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl ester	Anchusa strigosa	[50,51]
Retronecine 2S-hydroxy-2S(1R-hydroxyethyl)-4-methyl-pentanosyl ester	Anchusa strigosa	[50,51]
Rinderine	Anchusa 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]
Scorpioidine	Myosotis scorpioides	[159]
7-Senecioylhelotridine	Cynoglossum creticum	[70]
7-Senecioylhelotridine	Paracarum intermedium	[40]
7-Senecioylretronecine	Alkanna orientalis	[40]
	Echium hypertropicum	[92]
	Echium humile	[91]
9-Senecioylretronecine	Alkanna orientalis	[40]
9-Senecioylretronecine	Echium humile	[91]
7-Senecioylrinderine	Paracaryum intermedium	[40]
7-Senecioyllycopsamine	Echium humile	[91]
Sincamidine	Amsinckia intermedia	[44]
Senkirkine	Trichodesma ehrenbergii	[54]
Strigosine	Heliotopium strigosum	[25,141]
Subulacine	Heliotopium angiospermum	[29]
	Heliotopium molle	[29]
	Heliotopium subulacatum	[29]
	Heliotopium ternatum	[27]
	Heliotopium transalpinum var. transalpinum	[145]
Supinine	Amsinckia 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]
Supinidine	Heliotropium 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 ester	Anchusa strigosa	[50,51]
Symlandine	Amsinckia menziesii var. inermedia	[42]
	Echium sericeum	[54]
	Symphytum × uplandicum	[180]
Symphytine	Myosotis 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]
Symviridine	Symphytum asperum	[172]
	Symphytum officinale	[172,177]
	Symphytum × uplandicum	[172]
Tessellatine	Amsinckia 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]
Thesinine	Borago officinalis	[56]
Thesinine-4'-O-β-D-glucoside	Borago officinalis	[56]
7-Tigloyl-9-(2-deoxy-2-methyl)echimidinylheliotridinEchium	Cynoglossum columnae	[69]
7-Tigloyl-9-(2,3-dihydroxybutyryl)retronecine	Echium horridum	[90]
	Echium rauwolfii	[90]
	Echium setosum	[96]
	Echium vulgare	[96]
7-Tigloyl-9-(2,3-dihydroxypropanoyl)retronecine	Alkanna orientalis	[40]
7-Tigloyl-9-(2,3-dihydroxypropanoyl)retronecine	Alkanna tincotoria	[40]
7-Tigloylheliotridine	Cynoglossum officinale	[67]
7-Tigloyllycopsamine	Echium horridum	[90]
7-Tigloyllycopsamine	Echium rauwolfii	[90]
7-Tigloyl-9-(2-methybutyryl)retronecine	Echium horridum	[90]
	Echium rauwolfii	[90]
	Echium setosum	[96]
	Echium vulgare	[96]
7-Tigloylretronecine	Alkanna tinctoria	[40]
	Arnebia decumbens	[40]
	Echium amoenum	[87]
	Echium setosum	[96]
	Echium vulgare	[96]
9-Tigloylretronecine	Alkanna orientalis	[40]
	Alkanna tincotoria	[40]
	Arnebia decumbens	[52]
	Echium horridum	[90]
	Echium rauwolfii	[90]
	Echium setosum	[96]
	Echium vulgare	[96]
Trachelanthamidine	Heliotropium 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]
Trachelanthamine	Anchusa 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]
Trachelanthine	Trachelanthus hissaricus	[29]
Trachelanthine	Trachelanthus korolkovii	[150]
7-Trachelanthyl-laburnine	Rindera umbellata	[169]
7-Trachelanthylretronecine	Amsinckia vernicosa	[42]
Transalpinecine	Heliotropium transalpinum var. transalpinum	[145]
Triangularine	Alkanna orientalis	[40]
Triangularine	Alkanna tinctoria	[40]
Triangularicine	Alkanna orientalis	[40]
Triangularicine	Alkanna tinctoria	[40]
Trichodesmine	Heliotropium arguzioides	[28]
	Trichodesma africanum	[40,181]
	T. incanum	[46]
Turkestanine	Rindera baldschuanica	[152]
	Rindera oblongifolia	[152]
	Solenanthus turkestanicus	[135,150]
Uplandicine	Echium rauwolfii	[90]
	Echium setosum	[96]
	Echium vulgare	[96]
	Onosma arenaria	[163]
	Onosma stellulatum	[167]
	Symphytum × uplandicum	[180]
Uluganine	Ulugbekia tshimganica	[183]
Viridantine	Cynoglossum furcatum	[76,187]
Viridantine	Onosma erecta	[69]
Viridiflorine	Anchusa 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-Viridiflorylretronecine	Echium tuberculatum	[60]
	Eritrichium rupestre	[60]
	Nonnea lutea	[60]
	Nonnea setosa	[60]
	Onosma stellulatum	[60]
Vulgarine	Echium 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 4. Mass spectrum of 9-acetyltrachelanthamidine.

Figure 5. Mass spectrum of 7-acetylretronecine/7-acetylheliotridine.

Figure 6. Mass spectrum of viridiflorine/trachelanthamine.

Figure 7. Mass spectrum of 9-angeloyl or 9-tigloylretronecine 9-angeloyl or 9-tigloylheliotridine.

Figure 8. Mass spectrum of amabiline.

Figure 9. Mass spectrum of 9-curassavoylheliotridine.

Figure 10. Mass spectrum of heliotrine.

Figure 11. Mass spectrum of lycopsamine/intermedine/indicine/echinatine/rinderine.

Figure 12. Mass spectrum of 7-acetyllycopsamine/7-acetyl intermedine/7-acetyl indicine/ 7-acetyl echinatine/7-acetyl 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.

Figure 14. Mass spectrum of echimidine/heliosupine.

Figure 15. Mass spectrum of 3'-acetylechimidine/3'-acetylheliosupine.

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.	Alkaloid	RI	[M]⁺	Characteristic ions m/z (relative abundance)	References
1	3'-Acetylcanescine	-	441	441(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]
2	3'- Acetylcanescenine	-	441	441(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]
3	7-Acetyl-9-curassavoylheliotridine	2275	355	295(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]
4	7-Acetyl-9-(2,3-dihydroxybutryl) retronecine	2092	299	239(3), 181(20), 180(100), 136(20), 120(59), 101(20), 94(32), 93(73), 80(12), 67(5), 55(5), 43(15).	[163]
5	7-Acetyl-9-(2,3-dimethylbutryl) retronecine	1947**	295	235(8), 180(100), 136(20), 120(36), 101(30), 94(30), 93(65), 80(8), 43(42).	[163]
6	3'-Acetylechinatine	2220	341	326(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]
7	7-Acetylechinatine	2235	341	341(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]
8	3'-Acetylechiumine	2245*	423	423(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]
9	3'-Acetylechimidine	2640	439	439(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]
10	5'-Acetyleuropine	-	371	156(18), 138(100), 94(36), 93(75), 59(74).	[138]
11	7-Acetyleuropine	-	371	371(2.7), 356(1), 311(3), 282(5), 180(100), 120(72), 93(65), 80(17), 59(95).	[110]
12	3'-Acetylfurcatine	3188*	425	223(28), 222(100), 143(10), 136(36), 121(15), 120(82), 94(27), 93(61), 85(21), 80(7), 57(63).	[42]
13	3'-Acetylheliosupine	2640	439	424 (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]
14	7-Acetyl-9-(2-hydroxy-3-methylbutryl) retronecine	2024**	297	237(5), 180(100), 136(25), 120(52), 119(20), 101(25), 94(45), 93(95), 80(15), 43(35).	[163]
15	3'-Acetylindicine	2195	341	341(2), 255(2), 181(5), 138(100), 93(48), 43(10).	[158]
16	3'-Acetylintermedine	2255	341	341(5), 298 (4), 255 (16), 139(20),138(100), 137 (12),136 (12), 94 (30), 93 (71), 80 (10), 43 (21).	[40]
17	7-Acetylintermedine	2220	341	296(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]
18	5'-Acetyllasiocarpine	-	453	363, 335, 321, 263, 220(100), 141, 136, 121, 120, 119, 106, 94, 93, 83, 80.	[186]
19	3'-Acetyllithosenine	-	457	457(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]
20	3'-Acetyllycopsamine	2255	341	341(5), 298(4), 255(16), 139(20), 138(100), 137(12), 136(12), 94 (30), 93(71), 80 (10), 43(21).	[40]
21	7-Acetyllycopsamine	2230	341	341(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]
22	7-Acetyl-9-(2-methylbutyryl) retronecine	1914**	281	221(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]
23	3'-Acetylmyscorpine	3290*	423	221(30), 220(100), 136(47), 120(67), 119(35), 94(39), 93(51), 83(32), 80(19), 55(39).	[42]
24	7-Acetylretronecine	1532**	197	180(3), 137(12), 111(40), 106(30), 94(20), 80(100), 68(3), 43(30).	[163]
25	3'-Acetylrinderine	2222	341	326(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]
26	7-Acetyl-9-(sarracinoyl) retronecine	2125	295	235(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]
27	7-Acetylscorpioidine	-	423	423(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]
28	3'-Acetylsupinine	2080**	325	284(.02), 299(10), 136(10), 122(100), 120(48), 108(13), 101(13), 93(50), 80(13), 70(9), 53(6), 43(15).	[163]
29	3'-Acetyltessellatine	3064*	341	341(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]
30	9-Acetytessellatine	2962*	341	341(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]
31	3'-Acetyltrachelanthamine	-	327	327(1), 284(2), 240(6), 184(6), 142(27), 125(38), 124(100), 84(14), 83(59), 82(54).	[128]
32	9-Acetyltrachelanthamidine	1395	183	140(8), 125(8), 124(100), 110(5), 95(10), 83(50), 82 (27), 55(23).	[40]
33	3'-Acetylviridiflorine	2767*	327	327(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]
34	9-(3'-Acetylviridifloryl) retronecine	-	341	341(4.7), 255(3), 182(5), 157(4), 138(100), 120(10), 93(92), 85(4), 83(20), 80(16), 43(38).	[119]
35	9-(3'-Acetyl)viridifloryl turneforcidine (or isomer)	3050*	343	343(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]
36	7- Acetylvulgarine	-	439	440(M⁺+ 1), 422(40), 380(15), 358(5), 340(65), 296(42), 282(85), 180(100).	[11]
37	Amabiline	1985, 2652*	283	383(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]
38	Anadoline	-	381	381(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]
39	7α-Angeloyl-1-chloromethy-1,2-dihydropyrrolizidine	1815	255	220(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]
40	7-Angeloyl-9-(2,3-dihydroxybutyryl)heliotridine	2333	339	339(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]
41	7-Angeloyl-9-(2,3-dihydroxybutyryl)retronecine	2315	339	339(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]
42	7-Angeloyl-9-(2,3-dihydroxypropanoyl)retronecine	2300	325	294(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]
43	7-Angeloyl-1-formyl-6,7-dihydro-5H-pyrrolizidine	1920	233	215(3), 150(100), 134(92), 133(35), 122(4), 106(15), 105(38), 104(15), 83(10), 79(16), 55(20). 46	[67]
44	7-Angeloyl-9-(hydroxypropenoyl)retronecine	2053	307	221(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]
45	7-Angeloylechinatine	2467	381	336(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]
46	7-Angeloylheliotridine	1820	237	219(1), 154(2), 137(42), 136(20), 124(25), 111(35), 106(86), 94(25), 83(10), 80(100), 68(10), 55(20).	[70]
47	7-Angeloylheliotine	-	395	395(5), 295(7), 220(100), 136(57), 120(80), 119(70), 93(43), 83(34), 59(55), 43(18).	[127]
48	7-Angeloyllycopsamine	2460*	381	381(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]
49	7-Angeloyl-9-(2-methylbutyryl)heliotridine	2180	321	321(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]
50	7-Angeloyl-9-(2-methylbutyryl)retronecine	2155	321	221(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]
51	7-Angeloylretronecine	1787	237	237(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]
52	9-Angeloylretronecine	1797	237	237(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]
53	7-Angeloylrinderine	2465	381	381(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]
54	9-Angeloyltrachelamthamidine	1700	223	140(1), 125 (30), 124(100), 123(20), 122(15), 110(4), 95(13), 83(45), 82(16), 70(6), 55(27).	[40]
55	9-Angeloyl-7-viridiflorylretronecine	-	381	220(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]
56	Asperumine	-	397	380, 336, 220, 138, 120.	[203]
57	9-(Butyryl-2-ene) supinidine	1674**	207	180(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]
58	Canescine	-	399	399(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]
59	Canescenine	-	399	399(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]
60	Coromandaline	-	285	285(2), 267(7), 241(3), 240(9), 142(65), 125(23), 124(100), 83(28), 82(18).	[140]
61	Coromandalinine	-	283	283(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]
62	Cryptanthine		353	354[M⁺+1](1), 272(2), 254(3), 238(2), 138(2), 120(100), 118(2).	[65]
63	Curassanecine	-	157	126(14), 98(10), 83(100) 82(23).	[117]
64	Curassavine	-	299	299(0.7), 281(1.4), 255(2.6), 254(5), 142(80), 125(27), 124(100).	[140]
65	Curassavinine	-	297	297(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]
66	9-Curassavoylheliotridine	2190	313	295(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]
67	Cynaustine	-	283	C₁₅H₂₅NO₄, 122(100).	[68]
68	Cynaustraline (or stereoisomer)	2682*	285	285(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]
69	Cynoglossamine	-	445	147(100), 138(27), 119(17), 93(23).	[138]
70	5-Deoxylasiocarpine	-	395	396[M + H] ⁺ (2), 295(5.5), 363(1), 220(80), 120(83), 93(68), 83(32).	[123]
71/72	3',7-Diacetylintermedine/3',7-Diacetyllycopsamine	2340	383	340(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]
73	3',9-Diacetyltessellatine	3090*	383	383(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]
74	5,6-Dihydro-7,9-dimethoxy-7H-pyrrolizine	1415**	181	150(90), 134(5), 120(100), 119(35), 106(12), 91(3), 79(5).	[163]
75	Dihydroechinatine	-	301	MS², 284, 258, 240, 140, 122, 96.	[167]
76	thero-2'',3''-Dihydroxyechiumine	-	415	415(0.5), 371(2), 254(56), 210(26), 166(5), 138(30), 136(37), 120(100), 93(70).	[63]
77	Dihydroxytriangularine	2525	369	338(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]
78	Dihydroxytriangularicine	2525	369	338(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]
79	Echihumiline	2578	397	397(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]
80	Echimidine	2560	397	397(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]
81	Echimidine isomer (tigloyl)	2580	397	397(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]
82	Echinatine	2175	299	284(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]
83	Echiumine	3178*	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]
84	Echiuplatine		381	383[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]
85	Echiupinine	-	381	381(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]
86	Echivulgarine	-	479	480(M⁺+ 1), 462(35), 418(10), 398(10), 380(90), 336(40), 322(100), 220(70).	[11]
87	Ehretinine	-	275	275, 140(100), 123, 97.	[100]
88	2'',3''-Epoxyechiumine	-	397	254(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]
89	Erythro-2'',3''-chloro-2''-hydroxyechiumine	-	435	435(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]
90	1α-2α-Epoxy-1β-hydroxymethyl-8α-pyrrolizidine	-	155	126(4), 124(13), 96(10), 80(4), 71(50, 70(100), 68(10), 67(5), 56(6), 55(65).	[106]
91	Europine	2217	329	314(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]
92	Floridanine	-	441	426, 397, 382, 168, 152, 151(100), 150, 149, 123, 122, 110, 96, 94.	[62,204]
93	Floridimine	-	301	301(1), 239(8), 226(7), 142(36), 124(100), 95(12), 94(10), 83(55), 55(23).	[128]
94	Floridine	-	343	343(1), 328(2), 284(1), 240(2), 239(3), 225(10), 142(8), 124(100), 83(27).	[128]
95	Floridinine	-	301	301(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]
96	Furcatine	3138*	383	383(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]
97	Heleurine	1970	297	239(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]
98	Helibracteatine	-	255	255(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]
99	Helibractinecine	-	173	173(22), 156(4), 155(11), 142(7), 129(10), 124(1), 112(5), 99(83), 98(83), 95(6), 83(7), 82(100).	[111]
100	Helibracteatinecine	-	173	173(20), 156(4.5), 155(14), 142(3), 129(12), 124(1), 112(5), 99(85), 98(100), 82(83.5).	[112]
101	Helibracteatinine	-	255	255(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]
102	Helifoline	-	255	237(3), 156(5), 138(11), 137(3), 112(27), 111(100), 99(9), 98(42), 94(41), 83(9), 82(20), 80(24).	[136]
103	Helifolinecine	-	173	155(9.5), 129(67), 124(3), 116(6), 112(8), 98(100), 82(59), 80(10).	[136]
104	Helindicine	-	281	281(35), 207(100), 191(15), 149(37), 135(33), 109(34), 97(73), 95(55), 83(57), 81(46).	[130]
105	Heliocoromandaline	-	285	285(1), 267(4), 252(4), 240(6), 142(41), 125(17), 124(100), 84(63), 83(20), 82(15).	[117]
106	Heliocurassavine	-	299	299(1), 284(1), 281(1), 255(3), 254(10), 252(8), 243(7), 226(8), 142(48), 124(100), 83(56), 82(40).	[117]
107	Heliocurassavicine	-	285	285(1), 267(3), 252(3), 240(3), 142(49), 125(22), 124(100), 84(63), 83(58), 82(41).	[117]
108	Heliocurassavinine	-	285	285(1), 267(4), 252(4), 240(3), 142(55), 125(24), 124(100), 84(22), 83(48), 82(48), 81(36).	[117]
109	Heliospathine	-	313	313(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]
110	Heliospathuline	-	299	299(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]
111	Heliosupine	2553	397	382(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]
112	Heliotridine	1447	155	138(2), 111(55), 94(18), 80(100), 68(15).	[40]
113	Heliotridine 2S-hydroxy-2S(1S-hydroxyethyl-4-methyl-pentanoyl ester	-	313	MS2: 269, 270, 224, 156, 138, 120, 94.	[50]
114	Heliotrine	2100	313	255(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]
115	Heliovicine	-	285	267(5), 252(5), 240(4), 226(3), 175(1), 142(35), 124(100), 96(11), 95(9), 83(25), 82(20), 55(33).	[128]
116	Heliscabine	-	255	255(4), 156(42), 138(12), 111(100), 99(33), 98(92), 82(77), 80(10).	[139]
117	Hydroxymyoscorpine	-	397	397(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]
118	7-(Hydroxy-methylbutyryl)-9-viridifloryl retronecine	2560**	399	384(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]
119	Ilamine	-	313	314(M⁺ +1, 18), 224(6), 139(3), 122(52), 120(25), 93(20), 80(8), 59(100).	[115]
120	Incanine	-	337	294(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]
121	Indicine	2126	299	255(4), 156(11), 138(100), 93(95).	[158]
122	Isoechinatine (9-(+)-viridiflorylheliotridine)	-	299	299(11), 156(10), 139(33), 138(100), 137(14), 94(32), 93(68), 80(18).	[75,138]
123	Isolycopsamine	-	299	281(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]
124	Isoretronocanol enantiomer	1883*	141	141(20), 140(9), 124(13), 110(12), 108(11), 83(100), 82(56), 70(10), 68(11), 55(48).	[42]
125	9-(3'-Isovaleryl)viridifloryl retronecine	-	383	383(0.2), 255(3), 240(3), 223(5), 20194), 138(100), 120(10), 93(66), 85(28), 80(10), 57(19), 43(10),	[119]
126	Intermedine	2133	299	156(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]
127	Lactodine	-	227	227(9), 138(32), 137(41), 124(15), 111(60), 106(21), 94(44), 80(100).	[76,187]
128	Lasiocarpine	-	411	396(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]
129	Latifoline	-	393	393(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]
130	9-Latifolylretronecine	-	311	312(M⁺ +1, 40), 195(40), 161(20), 119(100).	[101]
131	Lepanthine	-	315	MS²: 298, 156, 138, 120, 94.	[166,167]
132	Lindelofine (or steroisomer)	2678*	285	285(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]
133	Lithosenine	-	415	415(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]
134	Longitubine	-	353	353(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]
135	Lycopsamine	2145	299	299(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]
136	Macrophylline	-	239	98, 83(100), 55.	[62]
137	Megalanthonine	-	301	301(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]
138	1-Methylene-8α-pyrrolizidine	1274	139	139(15), 95(100).	[205]
139	7-(2-Methylbutyryl)retronecine	1760	239	239(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]
140	9-(2-Methylbutyryl)retronecine	1795	239	239(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]
141	7-(2-Methylbutyryl)-9-(2,3-dihydroxybutyryl)retronecine	2285	341	341(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]
142	7-(2-Methylbutyryl)-9-echimidinyl retronecine	2512	399	399(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]
143	Monocrotaline	2268	325	236(35), 136(46), 120(100), 119(64), 93(36), 80(12), 43(69).	[195]
144	Myoscorpine	3212*	381	381(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]
145	Neolatifoline	-	393	393(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	-	285	ESIMS (positive mode) m/z 286.11966	[89]
147	(7S,8S)Petranine	-	285	ESIMS (positive mode) m/z 286.12162	[89]
148	Platynecine	-	157	113(18), 82(100), 68(18), 67(4), 55(27).	[106]
149	Platynecine N-Oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl ester	-	331	314, 288, 174, 156, 112.	[50]
150	Pycnanthine	2793	397	397(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]
151	Punctanecine	-	383	383(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]
152	Retronecine	1430 2190*	155	155(26), 138(2), 111(55), 94(15), 80(100), 68(15).	[40]
153	Retronecine dibenzoate	2785	363	363(0), 258(10), 241(20), 136(43), 119(55), 105(100), 94(60), 93(78), 77(35).	[207]
154	Retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanosyl ester	-	313	MS²: 396, 270, 224, 156, 138.	[50]
155	Retronecine 2S-hydroxy-2S(1S-hydroxyethyl)-[1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester,	-	471	ESIMS: m/z 472 [M + H]⁺ , for C₂₄H₄₁NO₈	[51]
156	Rinderine	2155	299	284(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]
157	Scorpioidine	-	381	381(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]
158	7-Senecioylhelotridine	1870	237	137(35), 136(18), 124(20), 111(35), 106(90), 94(21), 83(15), 80(100), 68(8), 55(18).	[70]
159	7-Senecioylretronecine	1816	237	237(4), 154(4), 137(30), 136(16), 124(25), 111(37), 106(40), 94(21), 83(23), 80(100), 68 (8), 55(15).	[91]
160	9-Senecioylretronecine	1833	237	237(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]
161	7-Senecioylrinderine	2515	381	336(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]
162	7-Senecioyllycopsamine	2497	381	336(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]
163	Sincamidine	-	313	C₁₆H₂₇NO₅(similar to heliotrine)	[44]
164	Senkirkine	2460	365	365(1), 266(10), 250(6), 222(9), 168(24), 153(41), 80(38), 43(100).	[54,195]
165	Subulacine	-	155	155(17), 126(4), 124(13), 96(10), 80(4), 71(5), 70(100), 68(10), 56(6), 55(65).	[106,208]
166	Supinine	1978	283	283(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]
167	Supinidine	1887*	139	139(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]
168	Supinidine N-oxide 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester	-	313	MS²: 296, 270, 224, 156, 138.	[50]
169	Symlandine	3194*	381	381(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]
170	Symphytine	3240*	381	381(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]
171	Symviridine	-	381	381(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]
172	Tessellatine	2930*	299	299(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]
173	7-Tigloyl-9-(2,3-dihydroxybutyryl)retronecine	2325	339	239(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]
174	7-Tigloyl-9-(2,3-dihydroxypropanoyl)retronecine	2320	325	237(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]
175	7-Tigloylheliotridine	1873	237	237(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]
176	7-Tigloyl-9-( hydroxypropenoyl) retronecine	2073	307	221(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]
177	7-Tigloyllycopsamine	2473*	381	336(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]
178	7-Tigloyl-9-(2-methybutyryl)retronecine	2170	321	221(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]
179	7-Tigloylretronecine	1816	237	237(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]
180	9-Tigloylretronecine	1843	237	193(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]
181	Trachelanthamidine	1853*	141	141(24), 140(10), 124(15), 110(9), 108(7), 83(100), 82(62), 70(8), 68(8), 55(45).	[42]
182	Trachelanthamine	1970	285	267(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]
183	Trachelanthamidine 2S-hydroxy-2S(1S-hydroxyethyl)-4-methyl-pentanoyl ester	-	299	ESIMS: m/z 300 [M + H]⁺, 142, 89, 83, 82, 55.	[51]
184	7-Trachelanthyl retronecine	2899*	299	299(12), 281(6), 236(11), 156(25), 138(50), 120(47), 111(45), 108(29), 106(40), 94(40), 93(320, 80(100).	[42]
185	Transalpinecine	-	173	98, 83, 70.	[145]
186	Triangularine	2375	335	237(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]
187	Triangularicine	2394	335	237(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]
188	Trichodesmine	2388	353	353(1), 264(56), 222(5), 136(36), 120(100), 93(23), 81(16), 43(40).	[195]
189	Turneforcidine	-	157	113(20), 82(100), 68(21), 67(6), 55(32).	[106]
190	Uluganine		399	399(2), 384(8), 356(1), 355(3), 354(2).	[183]
191	Uplandicine	2337	357	357(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]
192	Viridinatine	-	443	282(17), 138(41), 137(86), 124(32), 111(70), 106(42), 94(44), 80(100).	[76,187]
193	Viridiflorine	1983	285	284(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]
194	9-Viridifloryl turneforcidine (or isomer)	2394*	301	301(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]
195	Vulgarine	-	397	398[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.

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.
Alkaloid	C-1	C-2	C-3	C-5	C-6	C-7	C-8	C-9	C-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''	solvent	References
Necine Base
Helibractinecine	82.8	38.3	53.4	52.5	36.2	73.7	71.2	68.6														CDCL₃-CD₃OD	[111]
Helibracteatinecine	82.6	34.1	53.0	52.9	33.3	79.7	73.0	67.2														CDCL₃-CD₃OD	[112]
Turneforcidine	40.8	32.6	56.2	52.8	37.5	72.0	73.7	65.6														CD₃OD-ND₃	[222]
Transalpinecine	82.3	84.4	59.2	55.9	28.0	24.6	72.3	63.9														CD₃OD	[145]
Subulacine	70.9	63.4	54.0	58.4	27.1	26.2	67.9	60.2														CD₃OD	[145]
1α-2α-epoxy-1β-hydroxymethyl-8α-pyrrolizidine	83.7	65.2	62.3	56.2	27.9	25.0	72.1	64.0														CD₃OD	[145]
Tertiary base and N-oxide alkaloids
3'-Acetylcanescine	133.0	127.5	62.6	53.6	34.4	74.4	75.4	62.3	175.1	84.3	72.4-(CO:170.4), (Me: 21.2)	17.2	33.1	17.2	17.1	171.7	46.9	69.1	29.4	29.2		CDCL₃/D₆-DMSO	[154]
3'-Acetylcanescenine	133.0	127.5	62.6	53.6	34.4	74.4	75.4	62.3	175.1	84.3	73.7-(CO:170.4), (Me: 21.3)	16.0	33.1	17.8	14.2	171.7	46.9	69.1	29.4	29.2		CDCL₃/D₆-DMSO	[154]
3’-Acetylechihumiline N-oxide	133.0	124.9	79.4	70.5	33.9	73.3	95.6	63.0	174.7	85.6	74.8-(Me: 21.6)	61.1	74.0	27.3	26.4	166.8	116.2	161.9	28.0	21.0		CD₃OD	[166]
7-Acetylechinatine N-oxide	133.0	124.3	79.0	70.1	33.4	73.8	95.0	62.1	175.0	85.2	72.4	18.2	34.0	18.5	16.7	171.5	21.1					CD₃OD	[69]
7-Acetyleuropine	135.0	128.3	62.3	54.4	30.6	76.9	78.8	62.6	174.2	84.0	79.2- (OMe:56.8)	13.3	73.4	26.7	24.9	171.3	21.5					CDCL₃	[110]
3'-Acetylindicine	132.3	130.7	62.8	53.0	36.1	71.1	78.5	63.3	174.5	81.6	71.8-(CO:170.0), (Me 21.1)	14.3	32.3	17.2	16.3							CDCL₃	[158]
3'-Acetylindicine N-Oxide	132.4	121.9	78.0	69.6	34.7	69.6	95.8	62.1	173.8	81.9	72.4-(CO:170.3), (Me: 21.2)	14.0	33.0	17.3	16.8							CDCL₃	[158]
3'-Acetyllithonine	132.5	128.2	62.2	53.0	33.8	73.5	74.8	61.5	172.3	82.9	72.1-(CO:169.0), (Me: 20.5)	14.7	72.4	24.8	25.9	170.5	47.3	68.1	28.8	28.9		CDCL₃	[156]
3'-Acetylrinderine	135.0	128.4	61.9	54.2	34.0	75.2	80.4	62.4	174.3	81.8	72.5-(CO:110.2), (Me 13.9)	21.1	33.1	16.8	17.2							CDCL₃	[70]
3'-Acetyltrachelanthamine	44.7	30.4	54.1	54.9	25.6	31.5	67.8	67.9	174.3	81.6	72.2 -(CO: 169.7), (Me: 21.1)	13.9	32.8	16.7	17.2							CDCL₃	[128]
Canescine	133.0	127.5	62.6	53.6	34.4	74.4	75.4	62.3	175.1	84.3	69.5	17.2	33.1	17.2	17.1	171.7	46.9	69.1	29.4	29.2		CDCL₃/D₆-DMSO	[154]
Canescenine	133.0	127.5	62.6	53.6	34.4	74.4	75.4	62.3	175.1	84.3	71.1	16.0	33.1	17.8	14.2	171.7	46.9	69.1	29.4	29.2		CDCL₃/D₆-DMSO	[154]
Cryptanthine	133.9	125.8	62.9	53.9	34.7	75.4	75.6	60.7	167.7	127.4	139.3	16.0	20.6	175.4	77.4	71.4	16.7	22.6					[65]
Echihumiline	132.8	127.6	62.0	53.7	34.2	73.7	76.1	62.0	174.3	83.1	69.8	18.5	72.4	26.0	24.9	165.5	115.3	159.0	27.7	20.4		CDCL₃	[91]
Echimidine isomer	133.3	129	63.2	54.1	34.8	74.2	76	62.9	174.7	83.7	70.0	18.9	73.8	26.5	25.2	167.5	128.9	138.2	14.8	12.3		CDCL₃	[87]
Echiupinine	133.0	128.1	62.3	53.7	34.3	72.8	75.6	62.2	175.1	82.9	68.7	17.2	32.9	17.1	16.9	167.1	115.6	158.1	27.5	20.3		CDCL₃	[95]
Echiupinine N-oxide	131.8	128.1	78.2	69.1	34.3	71.4	93.7	60.2	174.9	84.0	69.4	16.9	33.2	17.5	17.2	166.2	114.5	160.3	27.6	20.6		CDCL₃	[95]
7-Epi-echimiplatine N-oxide	132.4	125.9	79.7	70.2	35.8	71.4	96.7	63.6	176.1	86.9	71.1	19.0	75.6	26.3	27.0							D₂O	[164]
2'',3''-Epoxyechiumine	noise	128.5	62.7	53.6	34.4	75.3	75.4	62.5	175.1	82.9	69.4	17.1	33.0	16.9	17.3	noise	77.2	60.0	13.6	19.3		CDCL₃	[63]
Erythro-3''-chloro-2''-hydroxyechiumine	132.6	127.8	62.4	53.7	34.5	75.4	75.8	62.3	173.6	83.0	69.4	16.9	33.0	17.1	17.3	175.1	77.2	62.8	17.9	23.0		CDCL₃	[63]
Floridine	44.2	31.2	54.0	54.0	25.4	29.5	67.6	66.2	173.4	83.4	72.7 -(CO: 169.6), (Me: 21.2)	15.1	73.5	26.2	24.9							CDCL₃	[128]
Floridinine	43.3	28.6	53.8	54.0	24.6	30.6	68.4	66.2	174.6	82.5	69.8	18.6	73.9	25.0	26.0							CDCL₃	[128]
Floridimine	44.3	28.7	54.2	54.3	25.3	30.6	67.6	63.2	174.7	84.1	69.9	18.6	73.8	26.0	24.9							CDCL₃	[128]
Helindicine	134.2	125.3	62.5	55.5	36.7	70.5	80.5	61.7	175.6	84.5	70.5	17.3	34.2	17.2	17.6							CD₃OD	[130]
Heliotridine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester	134.0	123.5	62.0	55.9	35.0	70.8	79.4	62.2	?	?	45.0	25.2	23.1	24.4	73.9-(8':17.4)							CD₃OD	[50]
Heliscabine	81.1	38.4	52.8	52.0	36.0	72.8	69.8	70.0	168.1	127.2	139.7	16.0	20.6									CDCL₃	[139]
Heliospathine	133.1	128.9	62.4	53.9	36.1	70.5	78.2	62.2	174.5	84.4	71.2	17.4	38.9	24.7	12.1-(8':11.9)							CDCL₃	[140]
Heliospathuline	139.1	124.2	62.4	53.9	34.8	76.5	76.2	59.3								174.3	83.8	72.4	16.5	31.9	15.6 (7'':17.2)	CDCL₃	[140]
Hydroxymyoscorpine	132.8	128.5	62.8	53.7	34.3	73.8	75.7	62.5	174.2	83.0	69.6	18.4	73.5	25.9	24.8	167.1	128.6	137.8	14.4	11.9		CDCL₃	[95]
Isoechinatine (9-(+)-viridiflorylheliotridine)	136.1	126.3	61.7	54.3	33.8	74.7	79.8	61.9	174.3	83.9	71.6	17.5	32.2	17.8	15.9							CDCL₃	[72,75]
Iso-lycopsamine	139.1	123.2	63.0	53.4	34.9	76.4	76.5	59.5								174.1	82.8	69.4	16.5	33.38	17.2 (7'':12.27)	CDCL₃	[133]
Lactodine	138.1	123.2	63.8	54.1	35.1	69.4	76.5	58.9	173.3	68.4	16.3											CDCL₃	[187]
Leptanthine	133.7	124.6	61.7	54.9	36.3	70.0	79.9	61.6	174.8	85.1	70.2	18.0	74.2	26.0	25.4							CD₃OD	[166]
Lithosenine N-oxide	133.7	124.0	78.0	69.7	36.3	71.2	96.8	62.5	175.5	86.1	71.2	19.1	75.2	27.0	26.3							CD₃OD	[166]
Lithosenine	133.0	126.9	62.2	53.1	33.8	73.4	74.8	61.4	173.5	83.4	68.9	18.0	72.5	24.7	25.9	170.3	47.5	68.1	28.9	29.0		CDCL₃	[156]
Megalanthonine	36.0	31.2	51.1	54.6	36.8	69.5	72.8	66.2	174.5	84.1	72.0	17.0	32.0	15.6	17.8							CDCL₃	[134]
Methylechiuplatine	133.5	128.0	62.9	54.0	34.7	73.6	76.1	61.3	171.3	44.9	69.7	44.8	172.2	51.8:OMe	27.3	166.9	127.7	139.2	15.9	20.6		CDCL₃	[65]
Myoscorpine	133.1	128.1	62.7	53.8	34.4	73.7	75.8	62.2	175.1	82.9	69.3	17.2	32.9	17.1	16.9	167.0	128.5	137.8	14.4	11.9		CDCL₃	[95]
Myoscorpine N-oxide	131.8	124.0	7 8.4	69.3	34.3	72.4	93.8	60.1	14.9	84.0	69.4	16.9	33.1	17.5	17.2	166.2	127.9	139.0	14.6	12.0		CDCL₃	[95]
Onosmerectine N-oxide	133.5	123.8	78.6	69.7	35.7	70.7	96.7	62.5	175.3	85.7	74.6	70.8	18.7	26.6	25.9							CD₃OD	[164]
(7S, 8R)-Petranine	134.4	121.1	70.9	63.4	34.7	70.2	87.7	59.8	167.5	126.9	140.3	16.1	20.6				68.8					CDCL₃	[89]
(7S, 8S)-Petranine	134.6	121.3	71.2	63.6	34.8	70.6	88.1	59.9	167.0	127.0	149.9	16.3	20.8				69.1					CDCL₃	[89]
Platynecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester	37.3	30.6	73.0	70.6	35.8	70.1	91.5	67.3	?	?	44.5	25.3	23.3	24.8	73.9-(8':17.4)							CD₃OD	[50]
Pycnanthine	132.8	126.0	62.2	53.9	34.2	72.4	75.8	61.7	174.4	83.6	71.3	15.8	32.0	17.7	17.0	165.5	112.4	160.1	66.8	30.3		CDCL₃	[91]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester	133.2	123.8	62.0	54.0	36.7	70.0	80.0	61.0	175.4	82.3	45.2	25.3	23.3	24.6	73.9-(8':17.6)							CD₃OD	[51]
Retronecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester	133.9	123.4	78.8	70.0	35.7	70.6	97.2	62.4	175.9	82.0	45.0	25.2	23.3	24.6	73.6-(8':17.7)							CD₃OD	[51]
Retronecine N-oxide 2S-hydroxy-2S-(1R-hydroxyethyl)-4-methyl-pentanoyl ester	134.0	123.4	78.8	70.0	35.8	70.6	97.0	62.0	175.5	81.0	44.0	25.8	23.9	24.3	74.0-(8':16.5)							CD₃OD	[51]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-2S-[(1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester	135.4	124.0	62.0	54.9	36.6	70.4	79.8	61.7	175.7	82.2	43.6	25.2	24.0	24.7	73.4-(8': 7.4)	180.0	81.3	45.0	25.2	23.1	24.7 (7'':73.6) (8'':17.0)	CD₃OD	[51]
Symviridine	133	127.8	62.7	53.8	34.3	72.7	75.8	62.3	174.4	83.4	70.7	17.1	32.9	17.7	16.0	166.9	115.5	158.2	27.5	20.3		CDCL₃	[172]
Supinidine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester	137.7	123.0	76.9	71.1	25.2	28.3	90.2	61.2	176.2	82.0	45.2	25.2	23.5	24.6	73.3-(8':17.6)							CD₃OD	[51]
Tessellatine	138.6	124.5	63.0	53.4	34.7	75.7	76.0	59.6								173.1	83.5	71.4	16.9	31.9	17.6 (7'':15.7)	CDCL₃	[42]
Threo-2'',3''-dihydroxyechiumine	132.9	125.0	63.3	54.0	34.8	74.9	75.8	63.0	174.9	83.2	69.8	16.9	33.2	17.2	17.2	175.4	78.7	71.5	16.5	22.1		CDCL₃	[63]
Trachelanthamidine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester	48.0	29.7	55.9	55.8	25.6	31.3	71.9	63.4	181.6	81.8	44.1	25.0	24.0	25.0	73.9-(8':17.4)							CD₃OD	[51]
Uplandicine	132.7	127.7	62.1	53.4	34.0	73.6	75.5	62.2	174.2	83.2	69.6	18.5	73.6	24.7	25.9	170.2	21.1	-	-	-		CDCL₃	[163]
Viridiflorine	44.5	31.5	54.5	54.2	25.5	30.0	67.8	67.2	174.4	83.6	71.0	17.2	32.1	17.9	15.9								[42]
Viridinatine	139.3	124.2	64.2	54.2	36.7	77.3	77.3	59.4	174.1	82.8	68.4	16.2	33.5	17.2	17.3	176.2	83.2	69.1	16.8	34.12	18.1 (7'':18.9)	CDCL₃	[187]
Viridinatine N-oxide stereoisomer	132.5	125.4	79.5	70.1	35.8	71.3	96.6	63.3	176.6	85.9	70.9	17.6	34.6	18.9	18.4	176.1	86.2	72.3	18.6	34.2	18, 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.
Alkaloid	H-1	H-2	H-3	H-5	H-6	H-7	H-8	H-9	H-3'	H-4'	H-5'	H-6'	C-7'	H-2''	H-3''	H-4''	H-5''	solvent	References
Necine Base
Helibractinecine [C₈H₁₅NO₃]		1.94	α 3.13 β 2.93	α 3.07 β 2.91	2.03	4.50	3.34	α 3.60 β 3.66										CDCL₃-CD₃OD	[111]
Helibracteatinecine [C₈H₁₅NO₃]		1.63	α 3.26 β 2.55	α 3.26 β 2.52	α 1.84 β 2.11	3.94	3.12	α 3.79 β 3.84										CDCL₃-CD₃OD	[112]
Turneforcidine [C₈H₁₅NO₂]	2.53	α 1.68 β 2.10	α 3.08 β 2.55	α 3.03 β 2.70	α 2.00 β 1.99	4.18	3.16	α 3.57 β 3.53										CD₃OD-ND₃	[222]
Transalpinecine [C₈H₁₅NO₃]		4.18	α 3.86 β 3.38	α 3.06 β 3.36	α 1.95 β 2.16	α 1.88 β 2.66	3.99	α 3.90 β 3.61										CD₃OD	[145]
Subulacine [C₈H₁₅NO₂]		3.95	α 3.79 β 3.38	α 2.97 3.62	α 1.96 2.24	α 2.19 2.26	4.45	α 3.97 β 3.79										CD₃OD	[145]
1α-2α-epoxy-1β-hydroxymethyl-8α-pyrrolizidine [C₈H₁₅NO₂]		4.59	α 3.81 β 3.89	α 3.23 β 3.50	α 2.08 β 2.23	α 2.00 β 2.30	4.31	α 3.93 β 3.69										CD₃OD	[145]
Tertiary base and N-oxide alkaloids
3'-Acetylcanescine [C₂₂H₃₅NO₈]		5.83	α 3.95 β 3.38	α 3.33 β 2.65	2.09	5.38	4.35	α 4.79 β 4.67	5.21-(COMe: 2.00)	1.19	2.00	0.94	0.91	2.45		1.26	1.26	CDCL₃/D₆-DMSO	[154]
3'-Acetylcanescenine [C₂₂H₃₅NO₈]		5.83	α 3.95 β 3.38	α 3.33 β 2.65	2.09	5.38	4.35	α 4.74 β 4.73	5.17 -(COMe: 2.03)	1.19	2.00	0.94	0.91	2.45		1.26	1.26	CDCL₃/D₆-DMSO	[154]
3’-Acetylechihumiline N-oxide [C₂₂H₃₃NO₉]		6.03	α 4.37 β 4.69	3.90 – 3.75 (m)	α 2.20 β 2.78	5.76	4.83	4.72	5.46 -(COMe: 1.98)	1.34		1.25	1.35	5.67	-	1.92	2.18	CD₃OD	[166]
3'-Acetylechinatine [C₁₇H₂₇NO₆]		5.76	α 3.37 β 3.92	α 2.68 β 3.30	α 1.91 β 1.98	4.17	3.96	α 4.78 β 4.96	5.21-(COMe: 2.04)	1.29	2.01	0.88	0.96					CDCL₃	[70]
7-Acetylechinatine N-oxide		6.00	α 4.70 β 4.38	α 3.83 β 3.79	α 2.74 β 2.23	5.69	4.88	4.78	3.96	1.42	2.17	0.90	0.93	2.06				CD₃OD	[164]
7-Acetyleuropine [C₁₈H₂₉NO₇]		5.81	α 4.02 β 3.38	α 3.28 β 2.86	1.93	5.09	4.16	α 4.93 β 4.87	3.81-(OMe: 3.27)	1.27		1.19	1.31	2.06				CDCL₃	[110]
3'-Acetylindicine [C₁₇H₂₇NO₆]		5.92	α 3.96 β 3.45	α 3.29 β 2.76	α 1.98 β 2.02	4.30	4.21	4.80	5.20 -(COMe: 2.04)	1.23	2.09	0.95	0.92					CDCL₃	[158]
3'-Acetylindicine N-Oxide [C₁₇H₂₇NO₇]		5.79	4.45	3.73-3.80	α 2.01 β 2.62	4.70	4.66	4.83	5.23 -(COMe: 2.03)	1.24	2.05	0.97	0.91					CDCL₃	[158]
3'-Acetyllithosenine [C₂₂H₃₅NO₉]		5.75	α 3.77 β 3.29	α 3.17 β 2.54	1.96	5.23	4.16	α 4.68 β 4.59	5.28 -(COMe: 1.87)	1.13		1.25	1.11	2.33		1.17	1.17	CDCL₃	[156]
3'-Acetylrinderine [C₁₇H₂₇NO₆]		5.76	α 3.37 β 3.92	α 2.68 β 3.30	α 1.91 β 1.98	4.21	3.96	α 4.66 β 4.93	5.28 -(COMe: 2.02)	1.25	2.01	0.92	0.98					CDCL₃	[70]
3'-Acetyltrachelanthamine [C₁₇H₂₉NO₅]	2.09	α 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	3.38	4.16	5.22 -(COMe: 1.97)	1.23	2.02	0.90	0.96					CDCL₃	[128]
Canescine [C₂₀H₃₃NO₇]		5.83	α 3.95 β 3.38	α 3.33 β 2.65	2.09	5.38	4.35	α 4.79 β 4.67	4.07	1.19	2.00	0.94	0.91	2.45		1.26	1.26	CDCL₃/ D₆-DMSO	[154]
Canescenine [C₂₀H₃₃NO₇]		5.83	α 3.95 β 3.38	α 3.33 β 2.65	2.09	5.38	4.35	α 4.74 β 4.73	3.89	1.19	2.00	0.94	0.91	2.45		1.26	1.26	CDCL₃/ D₆-DMSO	[154]
Cryptanthine		5.74	α 4.0 β 3.37	α 3.40 β 2.61	2.12	5.3	4.39	α 4.84 β 4.64	-	6.1	1.98	1.89		3.8	1.17	1.24		CDCL₃	[65]
5'-Deoxylasiocarpine [C₂₁H₃₃NO₆]		5.8	α 3.50 β 4.18	α 3.00 β 3.40	1.8	5.12	4.37	4.88	3.7 -(OMe: 3.22)	1.21	2.20	0.95	0.94		6.13	1.95	1.82	CDCL₃	[123]
Echihumiline [C₂₀H₃₁NO₇]		5.87	α 3.35 β 3.72	α 2.83 β 2.83	2.09	5.48	4.13	α 4.65 β 4.96	4.21	1.26	-	1.24	1.31	5.59	-	1.90	2.15	CDCL₃	[91]
Echihumiline N-oxide [C₂₀H₃₁NO₈]		5.97	α 4.54 β 4.77	α 3.73 β 4.13	α 2.24 β 2.89	5.77	5.45	α 4.71 β 4.94	4.22	1.27	-	1.25	1.30	5.57	-	1.92	2.17	CDCL₃	[91]
Echimidine isomer (tigloyl) [C₂₀H₃₁NO₇]		5.81	α 3.34 β 3.83	α 2.60 β 3.27	2.05	5.37	4.32	α 4.60 β 4.86	4.12	1.21		1.17	1.26	-	6.05	1.91	1.76	CDCL₃	[87]
7-Epi-echimiplatine N-oxide [C₁₅H₂₅NO₇]		5.89	α 4.42 β 4.21	α 3.74 β 3.59	α 2.47 β 2.01	4.67	4.55	4.78	4.18	1.14		1.16	1.21					D₂O	[164]
Floridine [C₁₇H₂₉NO₆]	2.23	α 2.15 β 2.15	α 3.75 β 2.77	α 3.48 β 2.65	2.04	α 2.20 β 1.70	4.01	α 4.16 β 4.27	5.45 -(COMe: 1.98)	1.36	-	1.25	1.40					CDCL₃	[128]
Floridinine [C₁₅H₂₇NO₅]	2.36	α 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	3.70	α 4.20 β 4.53	4.19	1.27	-	1.28	0.96					CDCL₃	[128]
Floridimine [C₁₅H₂₇NO₅]	2.30	α 2.17 β 2.28	α 3.89 β 2.83	α 3.59 β 2.89	2.11	α 2.26 β 1.80	4.30	α 4.35 β 4.45	4.26	1.32	-	1.28	1.33					CDCL₃	[128]
Helibracteatine [C₁₃H₂₁NO₄]		1.85	α 3.22 β 2.54	α 3.22 β 2.54	α 1.85 β 2.05	4.08	3.30	α 4.35 β 4.46	6.10	1.99	1.91							CDCL₃ + D₂O	[112]
Helibracteatinine [C₁₃H₂₁NO₄]		α 1.80 β 2.10	α 3.35 β 2.78	α 3.20 β 2.60	1.80	5.09	3.30	α 3.64 β 3.84							6.12	1.98	1.88	CDCL₃ + D₂O	[112]
Helindicine [C₁₅H₂₃NO₄]		5.94	α 4.40 β 3.92	α 3.97 β 3.34	2.15	4.63	4.90	α 4.98 β 4.80	4.05	1.17	2.03	0.95	0.93					CD₃OD	[130]
Heliotridine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₇NO₅]		5.95	3.70 4.18	3.10 2.64	2.10	4.52	4.60	4.85	1.74 1.79	1.82	0.87	0.99	3.78-(8':1.15)					CD₃OD	[50]
Heliscabine [C₁₃H₂₁NO₄]		1.86	α 3.42 β 3.05	α 3.30 β 3.05	2.16	4.66	3.64	α 4.25 β 4.35	6.10	1.99	1.89							CDCL₃	[139]
Ilamine [C₁₆H₂₇NO₅]		5.81	3.45 4.10	2.62 3.35	1.86	1.66 2.10	4.43	4.78	3.81	1.28		1.31	1.20 (8-OMe: 3.30)					CDCL₃	[115]
Ilamine N-oxide [C₁₆H₂₇NO₆]		5.81	α 3.43 β 4.55	α 3.48 β 3.79	α 1.99 β 1.89	2.50	4.81	α 4.85 β 4.69	3.80	1.26		1.29	1.22-(8-OMe:3.30)					CDCL₃	[115]
Isoechinatine (9-(+)-Viridiflorylheliotridine) [C₁₅H₂₅NO₅]		5.66	3.30 3.83	2.55 3.22	1.80 1.92	4.13	3.97	4.70 5.00	3.92	1.24	2.13	0.89	0.85					CDCL₃	[72,75]
Leptanthine [C₁₅H₂₅NO₆]		5.90	α 3.90 β 4.40	3.90	2.20	4.65	4.95	4.90	4.20 – Me 1.98	1.29	1.28	1.32							[166]
Leptanthine N-oxide [C₁₅H₂₅NO₇]		6.05	α 4.65 β 4.85	4.1 – 4.0 (m)	α 2.23 β 2.63	4.83	5.20	α 4.92 β 4.98	4.22 – Me 1.98	1.28	1.25	1.31							[166]
Lactodine [C₁₁H₁₇NO₄]		5.68	α 3.90 β 3.34	α 3.26 β 2.59	α 1.93 β 1.87	4.10	4.02	α 5.01 β 4.89	4.20	1.39								CDCL₃ + D₂O	[187]
Lithosenine [C₂₀H₃₃NO₈]		5.78	α 3.77 β 3.29	α 3.16 β 2.57	1.96	5.21	4.20	α 4.66 β 4.52	4.03	1.13		1.17	1.11	2.33		1.16	1.16	CDCL₃	[156]
Megalanthonine [C₁₅H₂₇NO₅]	2.78	α 1.89 β 2.15	α 3.26 β 2.61	α 3.21 β 2.73	α 2.03 β 2.14	4.29	3.48	α 4.09 β 4.46	2.64	-	2.64	3.70	1.34		6.80	1.96	1.80	CDCL₃	[134]
Methylechiuplatine [C₂₀H₂₉NO₇]		5.77	α 3.97 β 3.37	α 3.32 β 2.64	2.09	5.40	4.33	α 4.68 β 4.62											[65]
Neo coramandaline [C₁₅H₂₇NO₄]	1.9	α 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	3.56	α 4.30 β 4.20	3.98	1.23	2.14	0.88	0.92					CDCL₃	[74]
Onosmerectine N-oxide [C₁₅H₂₅NO₇]		5.96	α 4.66 β 4.45	3.87	α 2.58 β 2.12	4.75	4.85	α 4.92 β 4.88		4.22	1.26	1.31	1.27					CD₃O	[164]
(7S, 8R)-Petranine [C₁₄H₂₀CINO₃]		5.82	α 4.55 β 4.77	α 4.09 β 4.35	α 2.48 β 2.70	4.92	5.36	4.78	6.18	2.00	1.90			α5.42 β 5.75				CDCL₃	[89]
(7S, 8S)-Petranine [C₁₄H₂₀CINO₃]		5.83	α 4.54 β 4.78	α 4.09 β 4.35	α 2.51 β 2.69	4.94	5.38	4.88	6.20	2.02	1.90			α5.71 β 5.39				CDCL₃	[89]
Platynecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₉NO₆]	2.22	α 1.90 β 2.33	α 3.30 β 3.89	α 3.61 β 3.87	α 2.07 β 2.14	4.52	3.84	α 4.29 β 3.85	α 1.76 β 1.70	1.82	0.87	0.98	3.78-(8':1.15)					CD₃OD	[50]
Pycnanthine [C₂₀H₃₁NO₇]		5.83	α 3.55 β 4.06	α 2.80 β 3.50	2.15	5.47	4.12	α 4.65 β 4.75	3.99	1.26	2.15	0.93	0.85	5.92	-	3.65	2.06	CDCL₃	[91]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₇NO₅]		5.96	α 3.98 β 4.46	α 3.49 β 3.87	2.19	4.64	4.90	4.95	1.75	1.83	0.88	0.99	3.788'-1.17					CD₃OD	[51]
Retronecine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₇NO₆]		5.93	α 4.36 β 4.65	α 3.70 β 3.82	α 2.63 β 2.08	4.72	4.68	4.85	α 1.73 β 1.80	1.82	0.88	0.98	3.76-(8':1.16)					CD₃OD	[51]
Retronecine N-oxide 2S-hydroxy-2S-(1R-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₇NO₆]		5.95	α 4.36 β 4.60	α 3.70 β 3.85	α 2.60 β 2.08	4.72	4.69	4.82	α 1.66 β 1.47	1.74	0.88	1.00	3.91-(8':1.22)					CD₃OD	[51]
Retronecine 2S-hydroxy-2S-(1S-hydroxyethyl)-2S-[(1'S-hydroxyethyl)-4-methylpentanoyl]-4-methyl-pentanoyl ester [C₂₄H₄₁NO₈]		5.95	α 3.96 β 4.39	α 3.29 β 3.89	2.18	4.61	4.91	4.94	α 1.79 β 1.82	1.80	0.95	0.99	3.70-(8':1.16)	1.79	1.85	α 1.81 β 0.87	3.77-(6'':1.14)	CD₃OD	[51]
Symviridine [C₂₀H₃₁NO₆]		5.84	α4.02 β3.43	α 3.40 β 2.68	2.10	5.41	4.48	α 4.78 β 4.66	3.97	1.22	2.13	0.86	0.92	5.57	-	1.88	2.12	CDCL₃	[172]
Supinidine N-oxide 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₇NO₄]		5.90	α 4.36 β 4.56	α 3.61 β 3.67	α 2.08 β 2.38	2.50 2.03	4.66	4.77	α 1.73 β 1.80	1.83	0.88	0.98						CD₃OD	[51]
Trachelanthamidine 2S-hydroxy-2S-(1S-hydroxyethyl)-4-methyl-pentanoyl ester [C₁₆H₂₉NO₄]	2.28	1.90 2.27	α 3.22 β 3.48	α 3.74 β 3.12	2.08 2.19	2.25 1.97	3.99	3.69 3.63	1.77 1.69	1.83	0.94	1.00	3.77-(8':1.15)					CD₃OD	[51]
Uplandicine [C₁₇H₂₇NO₇]		5.83	α 3.38 β 3.93	α 2.70 β 3.35	2.06	5.34	4.43	α 4.62 β 4.87	4.14	1.22	-	1.26	1.19	1.98				CDCL₃	[163]
Viridinatine [C₂₂H₃₇NO₈]		5.71	α 3.80 β 3.30	α 3.16 β 2.19	α 1.92 β 1.85	5.48	4.10	α 4.98 β 4.76	3.90	1.28	2.15	0.86	0.93	-	3.95	1.32	2.14 (6'':0.90) (7'':1.00)	CDCL₃ + D₂O	[187]
Viridinatine N-oxide stereoisomer [C₂₂H₃₇NO₉]		5.86	α 4.51 β 4.22	α 3.73 β 3.61	α 2.45 β 2.00	4.67	5.57	4.75	4.04	1.04	1.89	0.75–0.78		-	3.93	1.10	2.05, 0.81	D₂O	[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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El-Shazly, A.; Wink, M. Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties. Diversity 2014, 6, 188-282. https://doi.org/10.3390/d6020188

AMA Style

El-Shazly A, Wink M. Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties. Diversity. 2014; 6(2):188-282. https://doi.org/10.3390/d6020188

Chicago/Turabian Style

El-Shazly, Assem, and Michael Wink. 2014. "Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties" Diversity 6, no. 2: 188-282. https://doi.org/10.3390/d6020188

APA Style

El-Shazly, A., & Wink, M. (2014). Diversity of Pyrrolizidine Alkaloids in the Boraginaceae Structures, Distribution, and Biological Properties. Diversity, 6(2), 188-282. https://doi.org/10.3390/d6020188

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

Abstract

1. Introduction

2. Phytochemical Analysis of PAs

2.1. Mass Spectrometry

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

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

2.2. Nuclear Magnetic Resonance (NMR)

2.3. Enzyme-Linked Immunoassay

3. Tissue Culture

4. Variation of PAs between Plant Organs and Developmental Stages

5. Biological Activity of PAs

5.1. Antimicrobial Activity

5.2. Sequestration in Insects and Antifeedant Properties

5.3. Biological Importance

6. Chemotaxonomic Information of PAs in Boraginaceae

6.1. Genus Amsinckia

6.2. Genus Cynoglossum

6.3. Genus Echium

6.4. Genus Heliotropium

6.5. Genus Paracaryum and Paracynoglossum

6.6. Genus Rindera

6.7. Genus Symphytum

6.8. Other Boraginaceae Species

7. Conclusions

Acknowledgments

Author Contributions

Conflicts of Interest

References

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