A novel toxic alkaloid from poison hemlock (Conium maculatum L., Apiaceae): Identification, synthesis and antinociceptive activity

Radulović, Niko S.; Đorđević, Nevenka; Denić, Marija S.; Pinheiro, Mariana Martins Gomes; Fernandes, Patrícia Dias; Boylan, Fábio

doi:10.1016/j.fct.2011.10.060

Cited by 33 publications

(17 citation statements)

References 28 publications

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“…C 10 alkaloids are minor alkaloids. Conmaculatin is a relatively new finding that probably escaped detection in earlier analyses because of its low amounts. Hexanoyl‐CoA is a suitable starter, but may not be preferred naturally.…”

Section: Discussionmentioning

confidence: 98%

Polyketide synthases from poison hemlock (Conium maculatum L.)

et al. 2015

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Coniine is a toxic alkaloid, the biosynthesis of which is not well understood. A possible route, supported by evidence from labelling experiments, involves a polyketide formed by the condensation of one acetylCoA and three malonyl-CoAs catalysed by a polyketide synthase (PKS). We isolated PKS genes or their fragments from poison hemlock (Conium maculatum L.) by using random amplification of cDNA ends (RACE) and transcriptome analysis, and characterized three full-length enzymes by feeding different starter-CoAs in vitro. On the basis of our in vitro experiments, two of the three characterized PKS genes in poison hemlock encode chalcone synthases (CPKS1 and CPKS2), and one encodes a novel type of PKS (CPKS5). We show that CPKS5 kinetically favours butyryl-CoA as a starter-CoA in vitro. Our results suggest that CPKS5 is responsible for the initiation of coniine biosynthesis by catalysing the synthesis of the carbon backbone from one butyryl-CoA and two malonyl-CoAs.

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Section: Discussionmentioning

confidence: 98%

Polyketide synthases from poison hemlock (Conium maculatum L.)

et al. 2015

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“…In this synthesis the regioselective cleavage of N-tosylaziridines 1a-e by allylmagnesium bromide was achieved in almost quantitative yield. Thus, the obtained alkenes 2a-e were subjected to hydroboration using BH 3 •DMS (borane dimethylsulfide complex), followed by an oxidative cleavage of the borane adduct to provide 1,5-N-tosyl amino alcohols 3a-e. These were further cyclized using triphenylphosphine and diisopropyl azodicarboxylate (DIAD) via Mitsunobu condensation.…”

Section: Nucleophilic Substitutionsmentioning

confidence: 99%

“…Many of these compounds are attributed with pronounced biological/pharmacological activity. For example, coniine and γ-coniceine are the main toxic principles of one of the most poisonous members of the plant kingdom, Conium maculatum L. (poisonous hemlock) [2,3]; some 2-alkylpiperidines inhibit neuromuscular, ganglionic, central neuronal nicotinic acetylcholine receptors, HIV-protease, etc. [4,5].…”

Section: Introductionmentioning

confidence: 99%

Synthetic approaches to coniine and other 2-alkyl piperidines

Denić

Blagojević

Radulović

2013

Facta Univ Phys Chem Technol

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The first synthesis of coniine, a neurotoxic piperidine alkaloid found in poison hemlock (Conium maculatum L.), was performed back in 1886 by Ladenburg. Since that time, numerous different approaches to the synthesis of this and related alkaloids (2alkylpiperidines) have been developed. Nowadays, the enantioselective/specific synthesis of coniine is taken as a paradigm of the usefulness of new chiral synthetic methodologies. This review aims to summarize and systematize recent progress in the synthesis of coniine and related compounds.

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“…The synthetic work gives the desired compound in the amount that allows unobstructed structural elucidation, spectroscopic characterisation and the opportunity to test the biological activity of the compound in a number of assays. In this way, two new minor volatile compounds, conmaculatin and ternanthranin, were identified from two plant species, and they were found to be strong analgaesics (Radulović et al ., , ).…”

Section: Introductionmentioning

confidence: 97%