487-79-6Relevant articles and documents
Enantioselective total synthesis of (-)-α-kainic acid
Farwick, Andreas,Helmchen, Guenter
, p. 1108 - 1111 (2010)
(Figure Presented) An enantioselective total synthesis of (-)-α-kainic acid is described. Key steps are an lr-catalyzed allylic amination with a propargyllc amine to provide an enyne and a diastereoselective intramolecular Pauson-Khand reaction. Subsequent steps involve a Baeyer-Villiger reaction, reduction of the resulting lactone, and direct Jones oxidation of a silyl ether.
Algal neurotoxin biosynthesis repurposes the terpene cyclase structural fold into an N-prenyltransferase
Chekan, Jonathan R.,McKinnie, Shaun M. K.,Moore, Bradley S.,Noel, Joseph P.
, p. 12799 - 12805 (2020)
Prenylation is a common biological reaction in all domains of life wherein prenyl diphosphate donors transfer prenyl groups onto small molecules as well as large proteins. The enzymes that catalyze these reactions are structurally distinct from ubiquitous terpene cyclases that, instead, assemble terpenes via intramolecular rearrangements of a single substrate. Herein, we report the structure and molecular details of a new family of prenyltransferases from marine algae that repurposes the terpene cyclase structural fold for the N-prenylation of glutamic acid during the biosynthesis of the potent neurochemicals domoic acid and kainic acid. We solved the X-ray crystal structure of the prenyltransferase found in domoic acid biosynthesis, DabA, and show distinct active site binding modifications that remodel the canonical magnesium (Mg2+)-binding motif found in terpene cyclases. We then applied our structural knowledge of DabA and a homologous enzyme from the kainic acid biosynthetic pathway, KabA, to reengineer their isoprene donor specificities (geranyl diphosphate [GPP] versus dimethylallyl diphosphate [DMAPP]) with a single amino acid change. While diatom DabA and seaweed KabA enzymes share a common evolutionary lineage, they are distinct from all other terpene cyclases, suggesting a very distant ancestor to the larger terpene synthase family.
High-pressure Diels-Alder approach to natural kainic acid
Pandey, Sushil K.,Orellana, Arturo,Greene, Andrew E.,Poisson, Jean-Francois
, p. 5665 - 5668 (2006)
The first Diels-Alder based synthesis of (-)-kainic acid is described. Danishefsky's diene and a vinylogous malonate derived from 4-hydroxyproline combine under high pressure to afford a key bicyclic intermediate with virtually no loss of enantiopurity. This adduct can be converted into the natural product with complete stereocontrol.
Total Synthesis of (-)-α-Kainic Acid
Cooper, Jeremy,Knight, David W.,Gallagher, Peter T.
, p. 553 - 560 (1992)
N-Alkylation of the β-amino acid derivative 16, derived from (L)-aspartic acid, by the allylic chloride 12b followed by deprotection and lactonization leads to the nine-membered azalactone 18.Enolate Claisen rearrangement of this leads stereospecifically, via a boat-like transition state (cf. 6), to the pyrrolidine acid 19; subsequent one-carbon homologation, oxidation and deprotection affords (-)-(α)-kainic acid 1.
Enantioselective total synthesis of (-)-kainic acid and (+)-acromelic acid C: Via Rh(i)-catalyzed asymmetric enyne cycloisomerization
Lei, Honghui,Xin, Shan,Qiu, Yifan,Zhang, Xumu
, p. 727 - 730 (2018)
A diversity-oriented synthetic strategy was developed for the total synthesis of kainoid amino acids, which led to the enantioselective synthesis of (-)-kainic acid and the first total synthesis of (+)-acromelic acid C. Rh(i)-catalyzed asymmetric enyne cycloisomerization served as the key reaction in this strategy for the rapid construction of highly functionalized lactam, and the resulting vinyl acetate moiety was further utilized as a versatile building block for the installation of both isopropylidene and 2-pyridone units existing in natural kainoids.
Scalable Biosynthesis of the Seaweed Neurochemical, Kainic Acid
Chekan, Jonathan R.,McKinnie, Shaun M. K.,Moore, Malia L.,Poplawski, Shane G.,Michael, Todd P.,Moore, Bradley S.
, p. 8454 - 8457 (2019/05/21)
Kainic acid, the flagship member of the kainoid family of natural neurochemicals, is a widely used neuropharmacological agent that helped unravel the key role of ionotropic glutamate receptors, including the kainate receptor, in the central nervous system. Worldwide shortages of this seaweed natural product in the year 2000 prompted numerous chemical syntheses, including scalable preparations with as few as six-steps. Herein we report the discovery and characterization of the concise two-enzyme biosynthetic pathway to kainic acid from l-glutamic acid and dimethylallyl pyrophosphate in red macroalgae and show that the biosynthetic genes are co-clustered in genomes of Digenea simplex and Palmaria palmata. Moreover, we applied a key biosynthetic α-ketoglutarate-dependent dioxygenase enzyme in a biotransformation methodology to efficiently construct kainic acid on the gram scale. This study establishes both the feasibility of mining seaweed genomes for their biotechnological prowess.
Synthesis of (±)-β-Allokainic Acid
Piotrowski, Mathew L.,Kerr, Michael A.
, p. 3122 - 3126 (2019/06/08)
The total synthesis of kainoid alkaloid, (+/–)-β-allokainic acid is reported. The key step is a vinylogous Cloke–Wilson rearrangement followed by Lewis acid and transition metal induced transformations to prepare a highly functionalized pyrrolidine suitable for conversion to the target molecule.
Synthesis of Kainoids and C4 Derivatives
Tian, Zhenlin,Menard, Frederic
, p. 6162 - 6170 (2018/05/23)
A unified stereoselective synthesis of 4-substituted kainoids is reported. Four kainic acid analogues were obtained in 8-11 steps with up to 54% overall yields. Starting from trans-4-hydroxy-l-proline, the sequence enables a late-stage modification of C4 substituents with sp2 nucleophiles. Stereoselective steps include a cerium-promoted nucleophilic addition and a palladium-catalyzed reduction. A 10-step route to acid 21a was also established to enable ready functionalization of the C4 position.
Total synthesis of (-)-kainic acid and (+)-: Allo -kainic acid through SmI2-mediated intramolecular coupling between allyl chloride and an α,β-unsaturated ester
Suzuki, Junya,Miyano, Natsumi,Yashiro, Shunpei,Umezawa, Taiki,Matsuda, Fuyuhiko
, p. 6557 - 6566 (2017/08/16)
A 3,4-disubstituted pyrrolidine ring was effectively cyclized through SmI2-mediated reductive coupling between allyl chloride and an α,β-unsaturated ester, although little has been reported about SmI2-promoted C-C bond formation of an allyl chloride with an α,β-unsaturated ester. Selection of either the 3,4-cis- or 3,4-trans-selective cyclization can be accomplished simply by changing the additives from NiI2 to HMPA during reductive cyclization conducted in H2O-THF. Total synthesis of (-)-kainic acid and (+)-allo-kainic acid, which are pyrrolidine alkaloids used in neuroscience and neuropharmacology as useful molecular probes, was successfully achieved by using the stereo-complementary ring closure reactions promoted by SmI2 for the construction of the 2,3,4-trisubsituted pyrrolidine scaffold of kainoids.
Synthetic method of kainic acid
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Paragraph 0012, (2016/10/07)
The invention discloses a synthetic method of kainic acid. The synthetic method comprises the steps of carrying out single-step series connection N-allylation-SN2' reaction on (S)-5-oxo-tetrahydrofuran-3-carbamic acid benzyl ester as a raw material to construct a kainic acid core framework-trans-2,3-cis-3,4-trans-trisubstituted pyrrolidine intermediate, reducing and oxidizing an ester group in the intermediate into an aldehyde group, carrying out Horner-Wordsworth-Emmons reaction and mercury ion accelerated methanol hydrolysis reaction to obtain the ester group added with a carbon atom, finally carrying out ester exchange, oxidization and hydrolysis, so as to obtain kainic acid. The synthetic method has the beneficial effects that the raw material cost is low, the reaction steps are short, the operation process is simple and convenient, the total yield of kainic acid is high, the synthetic cost of kainic acid can be greatly lowered, and the industrial production of kainic acid is hopefully realized.
