Tremorgenic indole diterpenes from Ipomoea asarifolia and Ipomoea muelleri and the identification of 6,7-dehydro-11-hydroxy-12,13-epoxyterpendole A

Authors: Gardner, Dale; Welch, Kevin; Lee, Stephen; Cook, Daniel; RIET-CORREA, FRANKLIN - National Agricultural Research Institute(INIA)

Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/5/2018
Publication Date: 7/16/2018
Citation: Gardner, D.R., Welch, K.D., Lee, S.T., Cook, D., Riet-Correa, F. 2018. Tremorgenic indole diterpenes from Ipomoea asarifolia and Ipomoea muelleri and the identification of 6,7-dehydro-11-hydroxy-12,13-epoxyterpendole A. Journal of Natural Products. 81(7):1682-1686. https://doi.org/10.1021/acs.jnatprod.8b00257.
DOI: https://doi.org/10.1021/acs.jnatprod.8b00257

Interpretive Summary: Several different species of plants from the Ipomoea genus, commonly known as the morning glory plants, have been associated as causing a tremorgenic disease in livestock. Many of the plants from the this family have fungi that grow in a symbionic relationship with the plant, but also produce toxic compounds. From two of the plant species we have previously isolated and identified a number of toxic compounds known as indole diterpene alkaloids. Some of the compounds have been shown to cause a tremorgenic effect in mice and some do not. In an effort to better characterize the toxicological effects of the specific alkaloids we previously identified six of the major compounds were isolated in larger quantities in order to test in a mouse bioassay for tremorgenic activity. In addition, one of the isolated compounds was an unknown alkaloid and therefore its structure was fully characterized by spectroscopic methods. From the testing of the isolated indole diterpene alkaloids the tremorgenic activity of two compounds was verified as previously published, the tremorgenic activity of two other compounds was demonstrated for the first time, and then it was found that two others possessed no such tremorgenic effects in the mice. The findings from this study describe the structure of a new alkaloid from the plants and adds further data on the specific toxicology of this class of compounds and the relationship between chemical structure and biological activity. The data clearly supports the hypotheses that the indole alkaloids are responsible for the tremorgenic syndrome observed in livestock grazing these species.

Technical Abstract: Indole diterpene alkaloids have been isolated from Ipomoea asarifolia and I. muelleri associated with a tremorgenic syndrome in livestock. To better characterize the tremorgenic activity of the major indole diterpene alkaloids in these two plants, terpendole K (1), 6,7-dehydroterpendole A (2), 11-hydroxy-12,13-epoxyterpendole K (3), terpendole C (5), paxilline (6), and a new compound, 6,7-dehyro-11-hydroxy-12,13-epoxy-terpendole A (4) were isolated and evaluated for tremorgenic activity in a mouse model. Compounds 1, 3, 5 and 6 all showed similar and significant signs of tremorgenic activity. In contrast, the 11-hydroxy-12,13-epoxy compounds, 3 and 4, showed no significant tremorgenic activity.