Alkaloid Methyllycaconitine Research Articles

Three new toxic norditerpenoid alkaloids from the low larkspur Delphinium nuttallianum.

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 (1)H and (13)C NMR spectroscopy and HRMS. 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 LD(50) values for two of the new alkaloids (1 and 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, 2, and 7 were found to be comparable to that of 4, with calculated LD(50) values in mice of 5.7, 3.3, and 6.2 mg/kg, respectively.

Alkaloid Levels of a Tall Larkspur Species in Southwestern Alberta

Tall larkspurs (Delphinium spp.) are widely distributed in western North America and they kill more cattle on rangelands than any other poisonous plant. In Alberta, Canada, D. brownii Rydb. has a long history of causing cattle poisoning. The neurotoxic norditerpenoid alkaloid methyllycaconitine (MLA) was first detected in D. brownii over 50 years ago. A 2-year (1996 to 1997) survey was conducted on the levels of MLA in D. brownii collected at 5 sites in the foothills of southwestern Alberta. The vegetative stage of growth yielded the highest levels of MLA and the decline and change in concentration during that interval could be predicted on the basis of Julian day alone. The MLA levels during bud to pod development were not significantly different but they exceeded the reported levels for MLA in low larkspur by 5-to 10-fold. A new method is described for the determination of MLA by HPLC. DOI:10.2458/azu_jrm_v53i2_majak

Alkaloids of Delphinium poltoratskii.

Roots ofDelphinium poltoratskiiyield the known alkaloids methyllycaconitine, lycoctonine, anthranoyllycoctonine, ajacine, karacoline, and a new alkaloid delpoline, the structure of which was proved by spectral data and a direct correlation with karacoline. It has been found that the roots and the aerial part of the plant can provide raw material for the production of methyllycaconitine.

Alkaloid levels of a tall larkspur species in southwestern Alberta

Tall larkspurs (Delphinium spp.) are widely distributed in western North America and they kill more cattle on rangelands than any other poisonous plant. In Alberta, Canada, D. brownii Rydb. has a long history of causing cattle poisoning. The neurotoxic norditerpenoid alkaloid methyllycaconitine (MLA) was first detected in D. brownii over 50 years ago. A 2-year (1996 to 1997) survey was conducted on the levels of MLA in D. brownii collected at 5 sites in the foothills of southwestern Alberta. The vegetative stage of growth yielded the highest levels of MLA and the decline and change in concentration during that interval could be predicted on the basis of Julian day alone. The MLA levels during bud to pod development were not significantly different but they exceeded the reported levels for MLA in low larkspur by 5-to 10-fold. A new method is described for the determination of MLA by HPLC.

Ring E analogs of methyllycaconitine (MLA) as novel nicotinic antagonists

We have prepared ring E analogs of the diterpenoid alkaloid methyllycaconitine. These compounds have been assayed for nicotinic activity and were found to act as functional antagonists on adrenal nicotinic receptors.

ChemInform Abstract: Studies into the Synthesis of a Sub‐Unit of the Neurotoxic Alkaloid Methyllycaconitine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies into the synthesis of a sub-unit of the neurotoxic alkaloid methyllycaconitine

A potentially toxophoric subunit of methyllycaconitine has been synthesised from penta-1,4-dien-3-ol as the mixture of diastereomers 2a and 2b, in 14 steps and 5% overall yield.

ChemInform Abstract: A Tandem Horner‐Emmons Olefination‐Conjugate Addition Approach to the Synthesis of 1,5‐Disubstituted 6‐Azabicyclo(3.2.1)octanes Based on the AE Ring Structure of the Norditerpenoid Alkaloid Methyllycaconitine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

A Tandem Horner−Emmons Olefination−Conjugate Addition Approach to the Synthesis of 1,5-Disubstituted-6-azabicyclo[3.2.1]octanes Based on the AE Ring Structure of the Norditerpenoid Alkaloid Methyllycaconitine

A novel Horner-Emmons olefination conjugate addition reaction of N-acetylamides to form 1,5-disubstituted-6-azabicyclo[3.2.1]octanes with two bridgehead quarternary carbon centers is reported. This reaction is a key step in an approach to the synthesis of small ring analogues based on the AE ring structure of the Delphinium norditerpenoid, methyllycaconitine (MLA) (1). Initially, 3-(hydroxymethyl)cyclohex-2-en-1-one (10) was selected as the starting material to these structures, but its generation proved inefficient. In contrast, the synthesis of 3-[(phenylthio)methyl]cyclohex-2-en-1-one (6) and 3-(1,3-dithian-2-yl)cyclohex-2-en-1-one (11) proceeded in good yield. Subsequent hydrocyanation, ketalization, reduction, acetylation, deprotection of the acetal, and Horner-Emmons olefination-conjugate addition reaction to form 1-[(phenylthio)methyl]-5-[(ethoxycarbonyl)methyl]-6-acetamido-6-azabicyclo[3.2.1]octane (28), 1-(1,3-dithian-2-yl)-5-[(ethoxycarbonyl)methyl]-6-acetyl-6-azabicyclo[3.2.1]octane (29), respectively, are reported, as well as for readily available 3-methylcyclohex-2-en-1-one (12). Studies on the Pummerer rearrangement of 28 and subsequent desulfurization and reduction to form an hydroxymethyl-substituted azabicyclo[3.2.1.]octane (40) and then selective protection to form a protected hydroxyethyl N-ethyl (hydroxymethyl)azabicyclo[3.2.1]octane (3) are also described.

ChemInform Abstract: Synthesis of the A/E/F Tricyclic Section of the Norditerpenoid Alkaloid Methyllycaconitine, a Potent Inhibitor of Neurotransmission.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of the A/E/F tricyclic section of the norditerpenoid alkaloid methyllycaconitine, a potent inhibitor of neurotransmission

The tricyclic amine (±)-2; R = H, with five stereogenic centres, representing the A/E/F ring system of the norditerpene alkaloid methyllycaconitine, is synthesised from penta-1,4-dien-3-ol in nine steps, with overall yield 16%.

Alkaloid Levels in a Species of Low Larkspur and Their Stability in Rumen Fluid

A survey on the levels of the neurotoxic diterpenoid alkaloid methyllycaconitine (MLA) in low larkspur (Delphinium nuttallianum Pritz.) was conducted at rangeland sites in southern British Columbia. Freeze-dried plant samples representing vegetative, flower bud, and bloom stages of growth over 4 growing seasons were analyzed for MLA by high pressure liquid chromatography (HPLC). Differences in MLA concentration were found between sites (P 0.2). The vegetative stages of growth yielded the highest levels of MLA, approaching 1% of the dry matter at 1 site. On average, the reproductive stages of growth yielded half the amount of MLA as the vegetative stages. Differences in MLA levels between sites could not be attributed to the elevation or the weather during the growing season. It is suggested that topoedaphic effects may have an impact on low larkspur growth and toxicity. Preliminary results are also reported on the stability of MLA in bovine rumen contents. The alkaloid is not readily hydrolyzed in rumen contents and therefore is probably not detoxified by this pathway.

Normal phase liquid chromatographic analysis of toxic norditerpenoid alkaloids

AbstractA normal phase, isocratic, analytical high performance liquid chromatographic (HPLC) method has been developed for the analysis of toxic methylsuccinimidoanthranoyllycoctonine (MSAL) norditerpenoid alkaloids occurring in poisonous larkspurs (Delphinium sp.). The method has good sensitivity, specificity for MSAL norditerpenoid alkaloid and rapid analysis times. The technique employs 5 μm neutral alumina as the stationary phase and utilizes a mixture of hexane: 95% isopropyl alcohol as the mobile phase. Accurate and reproducible analyses can be performed on 1 g samples of plant material. The method has been applied to the analysis of the chemical phenology of the MSAL norditerpenoid alkaloids methyllycaconitine and 14‐deacetylnudicauline in three species of tall larkspurs (Delphinium barbeyi, D. occidentale, D. glaucescens). Analytical results confirm the primary occurrence of these toxic alkaloids in early vegetative tissues of these plants, their concentration in reproductive plant tissues and their reduction in level with plant maturation. The chemical phenology results further confirm the observed difference in the toxicity of the three tall larkspurs (D. barbeyi > D. glaucescens > D. occidentale) to livestock. Intraspecies differences of toxic alkaloid occurrence associated with site were also demonstrated.

Corumdephine ? A new alkaloid fromDelphinium corumbosum

The epigeal part ofDelphinium corumbosum Rgl., collected in the flowering phase in the environs of Pokatilovka (Dzhungarian Ala-Tau) has yielded — in addition to the known alkaloids methyllycaconitine, lycoctonine, delcorine, deoxydelcorine, delcoridine, dehydrodelcorine, dephatine, browniine, dictysine, and dictysine acetonide — a new diterpene alkaloid with the composition C25H39NO6 (I), which has been called corumdephine. The structure of corumdephine has been established on the basis of a passage from (I) to deoxydelcorine and spectral characteristics.