Submitted to: Journal of Natural Products
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: March 1, 2000
Publication Date: July 21, 2000
Citation: GARDNER, D.R., MANNERS, G.D., PANTER, K.E., LEE, S.T., PFISTER, J.A. THREE NEW TOXIC NORDITERPENOID ALKALOIDS FROM THE LOW LARKSPUR DELPHINIUM NUTTALLIANUM PRITZ. JOURNAL OF NATURAL PRODUCTS. 2000. Interpretive Summary: Three new toxic alkaloid compounds were isolated from the low larkspur Delphinium nuttallianum. The chemical structures of the three compounds were determined using proton and carbon nuclear magnetic resonance spectroscopy and chemical conversion to known acetate derivatives. The compounds were given the common names of bearline, 14-acetylbearline, and 16-deacetylgeyerline. To determine the toxicity of the compounds, bearlin and 14-acetylberline were tested using a mouse bioassay. The calculated lethal doses (LD50) were 5.7 and 3.3 mg/kg respectively. A previously known compound, geyerline, was also tested for toxicity was found to have an LD50 of 6.2 mg/kg. All three compounds are considered to be highly toxic and comparible to the toxicity of the well known neurotoxic alkaloid methyllycaconitine and sufficiently potent to warrant a thorough accounting of these compounds in considering the toxicity of the low and plains larkspur plants (Delphinium geyeri, D. nuttallianium, and D. andersonii).
Technical Abstract: Three new N-(methylsuccinimido)anthranoyllycoctonine norditerpenoids, given the names bearline (1), 14-acetylbearline (2) and 16-deacetylgeyerline (3), were isolated from the extract of the low larkspur Delphinium nuttallianum. The structures of the individual alkaloids were determined by 1H and 13C NM spectroscopy. These alkaloids are structurally related to the neurotoxic alkaloid methyllycaconitine (4) and may be important in establishing the toxicity of low larkspurs to cattle. A mouse bioassay was used to measure the LD50 for two of the alkaloids (1,2) as sufficient quantities of 3 were not available for toxicity testing. A structurally related alkaloid, geyerline (7), was isolated from D. geyeri in sufficient quantities for toxicity testing. The toxicities of 1, its 14-acetyl derivative (2) and 7 were found to be comparable to that of methyllycaconitine with calculated LD50 in mice of 5.7, 3.3, and 6.2 mg/kg respectively.