Names | |
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IUPAC name (1R,5S)-3-methyl-13-azatricyclo[7.3.1.05,13]tridecane | |
Other names Precoccinelline; Alkaloid 193C; 38211-56-2; (3abeta,6abeta,9abeta)-Dodecahydro-2alpha-methylpyrido[2,1,6-de]quinolizine; Pyrido(2,1,6-de)quinolizine, dodecahydro-2-methyl-, (2alpha,3abeta,6aalpha,9abeta)- | |
Identifiers | |
3D model (JSmol) | |
ChemSpider | |
PubChem CID | |
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Properties | |
C13H23N | |
Molar mass | 193.334 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Precoccinelline is an alkaloid produced by the Coccinella septempunctata , also known as the seven-spot ladybird. [1] The alkaloid is released from the joints in C. septempunctata legs when it is provoked to deter predators such as ants or birds. [2] [3] It binds to both insect and mammalian nicotinic acetylcholine receptors, giving it use as an insecticide or as a therapy to treat drug dependence. [4] [5]
It was determined that precoccinelline is produced de novo in the C. septempunctata as their diet, which is composed of aphids, does not contain this alkaloid. While the exact biosynthesis has not been fleshed out, precoccinelline is thought to be of polyketide origin. The hypothesized biosynthesis involves condensation of six acetates and methyl addition. [1]
2,6-lutidine (1) is used as starting material, and its treatment with β-bromo-propionaldehyde dimethyl acetal in ether produces a monolithium derivative. In the presence of 2,6-lutidine in excess, the monolithium derivative becomes an acetal (2). Treatment of the acetal with phenyl-lithium and then adding an ethereal solution of acetonitrile produces the crude ketone (3), followed by immediate transformation into the diacetal (4). Using sodium-isoamyl alcohol, the diacetal can be reduced to give the cis piperidine (5). The trans-isomer of the cis piperidine can be isolated and hydrolyzed using aqueous hydrochloric acid to yield the ketol (6). The ketol can then be cyclized with the use of acetic acid and pyrrolidine in refluxing tetrahydrofuran which gives a mixture of ketones. Separation of structure 7 from the mixture and then treatment with methyllithium in ether to produce a carbinol (8). Dehydrating the carbinol with thionyl chloride in methylene chloride gives olefin which can be hydrogenated to produce precoccinelline. [6]
Precoccinelline is an alkaloid which acts as an inhibitor of nicotinic acetylcholine receptors (nAChRs). It binds to an allosteric site on nAChRs― a site separate from the ACh recognition site. Of the secreted ladybird alkaloids, precoccinelline was the most potent inhibitor, acting via a non-competitive mechanism. [7]
Targeting nAChRs has several implications including developing insecticides and modulating drug dependence relating to the reward pathway in the brain. [4] [5]
Nicotine is a naturally produced alkaloid in the nightshade family of plants and is widely used recreationally as a stimulant and anxiolytic. As a pharmaceutical drug, it is used for smoking cessation to relieve withdrawal symptoms. Nicotine acts as a receptor agonist at most nicotinic acetylcholine receptors (nAChRs), except at two nicotinic receptor subunits where it acts as a receptor antagonist.
An acetylcholine receptor is an integral membrane protein that responds to the binding of acetylcholine, a neurotransmitter.
Muscarine, L-(+)-muscarine, or muscarin is a natural product found in certain mushrooms, particularly in Inocybe and Clitocybe species, such as the deadly C. dealbata. Mushrooms in the genera Entoloma and Mycena have also been found to contain levels of muscarine which can be dangerous if ingested. Muscarine has been found in harmless trace amounts in Boletus, Hygrocybe, Lactarius and Russula. Trace concentrations of muscarine are also found in Amanita muscaria, though the pharmacologically more relevant compound from this mushroom is the Z-drug-like alkaloid muscimol. A. muscaria fruitbodies contain a variable dose of muscarine, usually around 0.0003% fresh weight. This is very low and toxicity symptoms occur very rarely. Inocybe and Clitocybe contain muscarine concentrations up to 1.6%.
A parasympathomimetic drug, sometimes called a cholinomimetic drug or cholinergic receptor stimulating agent, is a substance that stimulates the parasympathetic nervous system (PSNS). These chemicals are also called cholinergic drugs because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. Common uses of parasympathomimetics include glaucoma, Sjögren syndrome and underactive bladder.
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral nervous system, muscle, and many other tissues of many organisms. At the neuromuscular junction they are the primary receptor in muscle for motor nerve-muscle communication that controls muscle contraction. In the peripheral nervous system: (1) they transmit outgoing signals from the presynaptic to the postsynaptic cells within the sympathetic and parasympathetic nervous system, and (2) they are the receptors found on skeletal muscle that receive acetylcholine released to signal for muscular contraction. In the immune system, nAChRs regulate inflammatory processes and signal through distinct intracellular pathways. In insects, the cholinergic system is limited to the central nervous system.
Epibatidine is a chlorinated alkaloid that is secreted by the Ecuadoran frog Epipedobates anthonyi and poison dart frogs from the Ameerega genus. It was discovered by John W. Daly in 1974, but its structure was not fully elucidated until 1992. Whether epibatidine is the first observed example of a chlorinated alkaloid remains controversial, due to challenges in conclusively identifying the compound from the limited samples collected by Daly. By the time that high-resolution spectrometry was used in 1991, there remained less than one milligram of extract from Daly's samples, raising concerns about possible contamination. Samples from other batches of the same species of frog failed to yield epibatidine.
Tubocurarine is a toxic benzylisoquinoline alkaloid historically known for its use as an arrow poison. In the mid-1900s, it was used in conjunction with an anesthetic to provide skeletal muscle relaxation during surgery or mechanical ventilation. Safer alternatives, such as cisatracurium and rocuronium, have largely replaced it as an adjunct for clinical anesthesia and it is now rarely used.
Anabasine is a pyridine and piperidine alkaloid found in the Tree Tobacco plant, as well as in the close relative of the common tobacco plant. It is a structural isomer of, and chemically similar to, nicotine. Its principal (historical) industrial use is as an insecticide.
Methyllycaconitine (MLA) is a diterpenoid alkaloid found in many species of Delphinium (larkspurs). In common with many other diterpenoid alkaloids, it is toxic to animals, although the acute toxicity varies with species. Early research was focused on identifying, and characterizing the properties of methyllycaconitine as one of the principal toxins in larkspurs responsible for livestock poisoning in the mountain rangelands of North America. Methyllycaconitine has been explored as a possible therapeutic agent for the treatment of spastic paralysis, and it has been shown to have insecticidal properties. Most recently, it has become an important molecular probe for studying the pharmacology of the nicotinic acetylcholine receptor.
Lobeline is a piperidine alkaloid found in a variety of plants, particularly those in the genus Lobelia, including Indian tobacco, Devil's tobacco, great lobelia, Lobelia chinensis, and Hippobroma longiflora. In its pure form, it is a white amorphous powder which is freely soluble in water.
A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.
α-Cobratoxin is a substance of the venom of certain Naja cobras. It is a nicotinic acetylcholine receptor (nAChR) antagonist which causes paralysis by preventing the binding of acetylcholine to the nAChR.
Neuronal acetylcholine receptor subunit alpha-4, also known as nAChRα4, is a protein that in humans is encoded by the CHRNA4 gene. The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAChR). Alpha4-containing nAChRs appear to play a crucial role in the addictive response to nicotine..
The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of nicotinic acetylcholine receptor implicated in learning, consisting of α4 and β2 subunits. It is located in the brain, where activation yields post- and presynaptic excitation, mainly by increased Na+ and K+ permeability.
Neuronal acetylcholine receptor subunit alpha-5, also known as nAChRα5, is a protein that in humans is encoded by the CHRNA5 gene. The protein encoded by this gene is a subunit of certain nicotinic acetylcholine receptors (nAchR).
Acetamiprid is an organic compound with the chemical formula C10H11ClN4. It is an odorless neonicotinoid insecticide produced under the trade names Assail, and Chipco by Aventis CropSciences. It is systemic and intended to control sucking insects (Thysanoptera, Hemiptera, mainly aphids) on crops such as leafy vegetables, citrus fruits, pome fruits, grapes, cotton, cole crops, and ornamental plants. It is also a key pesticide in commercial cherry farming due to its effectiveness against the larvae of the cherry fruit fly.
Catharanthine is a terpene indole alkaloid produced by the medicinal plant Catharanthus roseus and Tabernaemontana divaricata. Catharanthine is derived from strictosidine, but the exact mechanism by which this happens is currently unknown. Catharanthine is one of the two precursors that form vinblastine, the other being vindoline.
Dioscorine is an alkaloid toxin isolated from the tubers of tropical yam on several continents. It has been used as a monkey poison in some African countries, and as an arrow poison to aid in hunting in several parts of Asia. It was first isolated from Dioscorea hirsute by Boorsma in 1894 and obtained in a crystalline form by Schutte in 1897, and has since been found in other Dioscorea species. Dioscorine is a neurotoxin that acts by blocking the nicotinic acetylcholine receptor. Dioscorine is generally isolated in tandem with other alkaloids such as dioscin but is usually the most potent toxin in the mixture. It is a convulsant, producing symptoms similar to picrotoxin, with which it shares a similar mechanism of action.
The alpha-5 nicotinic acetylcholine receptor(α5 nAChR) also known as the α5 receptor is a type of ligand gated nicotinic acetylcholine receptor involved in pain regulation. One of the 5 transmembrane subunits of this receptor is the α5 subunit and is transcribed by the CHRNA5 gene. This receptor is commonly associated with nicotine addiction, immunotherapy, cancer, pain and attention.
Flupyradifurone is an organic heterocyclic compound. It is used as a novel butenolide insecticide. Flupyradifurone shows efficient protection to crops and is much safer for non-target organisms compared to other commercial insecticides. Flupyradifurone was developed by Bayer CropScience under the name Sivanto. Sivanto was launched in 2014 since it obtained its first commercial registration in central America. Insecticide Resistance Action Committee (IRAC) classified Flupyradifurone as 4D subset (butenolide) and it is the first pesticide in the butenolide category. In 2015, it was approved by EU.