Dehydropyrrolizidine alkaloids in two Cryptantha species: including two new open chain diesters one of which is amphoteric.
BACKGROUND
A livestock poisoning outbreak near Kingman, Arizona, USA, potentially linked to dehydropyrrolizidine alkaloids, prompted an evaluation of some local plants for the presence of these hepatotoxic alkaloids.


OBJECTIVE
To qualitatively and quantitatively examine two species of Cryptantha, a Boraginaceous genus previously shown to produce potentially toxic pyrrolizidine alkaloids, collected from the vicinity of Kingman, Arizona.


METHODS
Plant extracts were analysed using HPLC-electrospray ionisation (+)-MS and MS/MS to determine the presence of dehydropyrrolizidine alkaloid esters. Identities were confirmed by comparison of chromatographic and MS data with authenticated standards and, in the case of the previously undescribed alkaloids, using one- and two-dimensional NMR spectroscopy and high-resolution mass measurement.


RESULTS
Cryptantha inequata and C. utahensis were shown to produce retronecine-based dehydropyrrolizidine alkaloids at approximately 0.05% and 0.09% w/w respectively. Cryptantha inequata produced mainly echimidine, acetylechimidine and echiuplatine; dehydropyrrolizidine alkaloids that were previously associated with Echium plantagineum. The previously undescribed structure of echiuplatine was elucidated as an amphoteric, open chain diester with angelic acid and 3-hydroxy-3-methylglutaric acid. Along with lycopsamine, intermedine and dihydroxyechiumine, C. utahensis produced cryptanthine, a previously undescribed open chain diester alkaloid esterified with angelic acid and 2,3-dihydroxy-2-methylbutanoic acid. All pyrrolizidine alkaloids detected were present in the plants mainly as their N-oxides.


CONCLUSIONS
The retronecine-based alkaloids detected in both Cryptantha species herein investigated aligns them within the Krynitzkia subgenus. The dehydropyrrolizidine alkaloids detected are expected to be toxic but the low levels in the plants potentially mitigate the risk. The identification of the amphoteric echiuplatine provides a cautionary note with respect to the analysis of total dehydropyrrolizidine alkaloid content.
USDA, ARS, Poisonous Plant Research Laboratory, Logan, Utah, USA. steven.colegate@ars.usda.gov
Steven M
SM
Colegate
Dale R
DR
Gardner
T Zane
TZ
Davis
Joseph M
JM
Betz
Kip E
KE
Panter
D001130:Arizona; D028082:Boraginaceae / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015093:Meglutol / Q000032:analysis; D015394:Molecular Structure; D010087:Oxides / Q000737:chemistry; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry; D010947:Plants, Toxic / Q000506:poisoning; D011763:Pyrrolizidine Alkaloids / Q000032:analysis* / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry
D010087:Oxides; D010936:Plant Extracts; D011763:Pyrrolizidine Alkaloids; C014795:retronecine; D015093:Meglutol; C018336:indicine