Acids kainic

Another anthelmintic folk medicine used in Japan is the red algae Chondria armata belonging to the same family (Rhodomelaceae) with Digenea simplex. However, its use in this purpose has only been known from Tokunoshima, a small island located in the northeast of Okinawa. Its insecticidal property against flies has been noted by the residents of Yakushima, another island farther north. 

Domoic acid has been demonstrated to be responsible for the insecticidal activity of C. armata. It was 14 times more potent than DDT when administered subcutaneously into the abdomen of American cockroach. 

Domoic acid had never been known to be a causative agent of seafood poisoning until 1987 when an outbreak of serious poisoning with blue mussels (Mytilus edulis) occurred in Canada. 

More than 150 people were intoxicated by eating blue mussels cultured in eastern Prince Edward Island during a period from November to December 1987. The symptoms included nausea, vomiting, diarrhea, memory loss, disorientation, and coma. Three elderly patients died. In some cases, neurological symptoms such as memory loss persisted for more than 5 years. About a month after the first outbreak, Canadian scientists identified domoic acid as the causative agent by analysis of the contaminated mussels. 

The term amnesic shellfish poison (ASP) has been coined for this new shellfish toxin. The causative organism of ASP was then identified to be the pennate diatom Nitzschia pungens Grunow f. multiseries Hasle, a bloom of which contaminated the cultured mussels in eastern Prince Edward Island in 1987. 

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Similarly to alkenes. alkynes also insert. In the reaction of 775 carried out under a CO atmosphere in AcOH, sequential insertions of alkyne, CO. alkene. and CO take place in this order, yielding the keto ester 776[483]. However, the same reaction carried out in THF in the presence of LiCl affords the ketone 777, but not the keto ester[484]. The tricyclic terpenoid hirsutene (779) has been synthesized via the Pd-catalyzed metallo-ene carbonylation reaction of 778 with 85% diastereoselectivity as the key reaction[485], Kainic acid and allo-kainic acid (783) have been synthesized by the intramolecular insertion ol an alkene in 780, followed by carbonylation to give 781 and 782[486],... 

NMDA) (10), kaiaate from kainic acid [487-79-6] (11), and a-amiao-S-hydroxy-S-methjhsoxazole-Tpropionate (AMPA) (12). AH of the agonists, ie,... 

NMD A, kainic acid, and AMPA, are stimulants and convulsants (14). These agents are used only experimentally. 

Me2BBr, CH2CI2, —78°, 45 min, 100% yield. These conditions were chosen when conventional acid-catalyzed hydrolysis resulted in aldehyde epimerization during a kainic acid synthesis. ... 

Neuronal excitotoxicity AEA levels are elevated in the hippocampus of mice treated with kainic acid. 2-AG levels are elevated in rats treated with pilocarpine These are two animal models of epileptic seizures, where the endocannabinoids play an anti-convulsant and protective function Inhibitors of cellular re-uptake... 

Ogasawara and coworkers reported a concise route to (—)-kainic acid (Figure 6.51), an excitatory neurotransmitter of marine origin, via a lipase-mediated kinetic resolution of an N-Cbz aminocyclopentenol [139]. More recently, (—)-kainic acid was synthesized from an optically active butenolide prepared by enzymatic DKR [140]. 

Suggest a synthesis for amine (5), needed to make the potent neuronal excitant a-kainic acid. ... 

The next stage in the route to a-kainic acid was the alkylation of (5) with allylic halide (9). Even in... 

Partial seizure activity can be induced by the localised application of chemicals such as cobalt or alumina to the cortex or the injection of chemicals such as PTZ or kainic acid directly into particular brain areas like the hippocampus. 

Diastereoselective hydroformylation can be achieved in special cases through passive substrate control in which conformational preferences are transferred in the corresponding selectivity-determining hydrometalation step [4-6]. A recent example is the highly diastereoselective hydroformylation of a kainic acid derivative (Scheme 17) [64], The selective formation of the major diastereomer has been explained via a reactive substrate conformation in which allylic 1,2-strain has been minimized. In this situation the czs-positioned methylene carbonylmethoxy group controls the catalyst attack to occur from the si face exclusively. 

Scheme 17 Diastereoselective hydroformylation of a kainic acid derivative relying on passive substrate control...

Drucker-Colin R. Pedraza JG. (1983). Kainic acid lesions of gigantocellular... 

We recently showed that the iontophoretic injection of kainic acid (a glutamate agonist) in the SLD excites the PS-on neurons and induces a PS-like state (Boissard et al, 2002). Furthermore, the PS-like state induced by bicuculline iontophoresis in the SLD is reversed by the application of kynurenate, a... 

Zito, K.A., Vickers, G., Roberts, D.C. Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens. Pharmacol. Biochem. Behav. 23 1029, 1985. 

Pyrrolidine 2-548e was used as substrate for the synthesis of the natural product a-kainic acid [286, 287]. 

The synthesis of kainic acid, acromelic acid, and related compounds such as domoic acid has been the subject of considerable investigation.125 A simple and direct route to neurophysi-ologically active kainic acid analogs has been reported, as shown in Scheme 10.21.126... 

Reductive cleavage of the thiazoline C-S bond in heterocycle 193 with -Bu3SnH <1986T3537> followed by in situ hydrolysis of the resulting hemiaminal and protection of nitrogen as its benzyl carbamate gave 194 in 64% overall yield. This was then converted in several steps to potent marine neurotoxin Kainic acid 195 in racemic form (Scheme 27) <1994JOC2773>. 

Novel C-4 thiazole kainoid analogues have been synthesised from kainic acid 43. This was converted into the a-bromoketone 44 in three steps, which reacted with thioamides and thioureas to form thiazole and aminothiazole heterocycles 45. All the synthesised thiazole kainic acid derivatives exhibited strong binding to the kainate receptors <00BMCL309>. 

Intracerebroventricular injection of kainic acid has been shown to result in a well-characterized pattern of neuronal cell damage. In the hippocampus, kainic acid causes a selective lesion of the CA3 pyramidal neurons, an area rich in KA1 and GluR6 receptors. The lesion does not compromise passing axons, which is why this type of (excitotoxic) lesion is often referred to as axon-sparing . Kainic acid injection into the hippocampus also leads to epileptiform discharges in cells normally innervated by the damaged pyramidal neurons. 

A platelet-activating-factor-stimulated signal-transduction pathway is a major component of the kainic-acid-induced cyclooxygenase-2 expression in hippocampus 584... 

Both PAF [57] and COX-2 are potent mediators of the injury/inflammatory response (Fig. 33-5). PAF and COX-2 are also interrelated in neuronal plasticity. The PAF transcriptional activation of COX-2 may provide clues about novel neuronal cell-death pathways. In fact, the delayed induction of COX-2 by kainic acid precedes selective neuronal apoptosis by this agonist in the hippocampus [42,58]. 

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