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ARS Home » Pacific West Area » Logan, Utah » Poisonous Plant Research » Research » Publications at this Location » Publication #316820
Title: Hydroxylic solvent-induced ring opening of the dehydropyrrolizidine alkaloids riddelliine and seneciphylline: Implications for toxicity and analytical studies

Author
item Colegate, Steven
item Gardner, Dale
item Resager, William
item BOLLAR, N - Volunteer
item BETZ, J - National Institutes Of Health (NIH)
item Panter, Kip

Submitted to: International Journal of Poisonous Plant Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/15/2015
Publication Date: 8/1/2017
Citation: Colegate, S.M., Gardner, D.R., Resager, W.C., Bollar, N., Betz, J.M., Panter, K.E. 2017. Hydroxylic solvent-induced ring opening of the dehydropyrrolizidine alkaloids riddelliine and seneciphylline: Implications for toxicity and analytical studies. International Journal of Poisonous Plant Research. 4:1-15.

Interpretive Summary: The dehydropyrrolizidine alkaloid riddelliine is often used in toxicology studies. However, a solution of riddelliine in methanol or ethanol was observed to undergo a transformation. Isolation of the major riddelliine –methanol adduct and subsequent 1D and 2D NMR spectroscopic analysis unambiguously determined that the methanol adds to the riddelliine in a ring-opening transesterification at the allylic C9 ester bond forming a new C7 monoester of retronecine with methylriddelliic acid. The spontaneous formation of riddelliine and seneciphylline adducts should be checked prior to using solutions of riddelliine and seneciphylline, or their N-oxides, as analytical standards or for toxicological studies.

Technical Abstract: etabolites that can also cause various cancers in animal models. Riddelliine and seneciphylline are closely-related, macrocyclic diester dehydropyrrolizidine alkaloids produced by various species in the Asteraceae. Despite the evidence of carcinogenicity in animal models, and the increasing concerns with respect to human health, riddelliine and lasiocarpine are the only dehydropyrrolizidine alkaloids so far officially described as Group 2B carcinogens. This, combined with the ready accessibility of quite pure riddelliine from some plant sources, has led to riddelliine often being used in toxicology studies. A routine HPLC-esi(+)MS analysis of a stored, standard solution of riddelliine in methanol revealed the formation of two new isobaric (m/z 382) peaks at slightly longer retention time. A similar formation of two new isobaric (m/z 396) peaks was observed for riddelliine in ethanol. The methanol- and ethanol-related compositional changes were also observed with seneciphylline and the N-oxides of riddelliine and seneciphylline but not with retrorsine, senecionine, heliotrine or the N-oxides of senecionine and heliotrine. There was no evidence for complete hydrolysis of the alkaloids to the retronecine base. Isolation of the major riddelliine –methanol adduct and subsequent 1D and 2D NMR spectroscopic analysis unambiguously determined that the methanol adds to the riddelliine in a ring-opening transesterification at the allylic C9 ester bond forming a new C7 monoester of retronecine with methylriddelliic acid. The spontaneous formation of riddelliine and seneciphylline adducts should be checked prior to using solutions of riddelliine and seneciphylline, or their N-oxides, as analytical standards or for toxicological studies.