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postgraduate thesis: Studies towards syntheses of kainic acid

TitleStudies towards syntheses of kainic acid
Authors
Advisors
Advisor(s):Yang, D
Issue Date2012
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Xu, S. [许少波]. (2012). Studies towards syntheses of kainic acid. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979941
AbstractKainoid amino acids are a family of none proteinogenic pyrrolidine dicarboxylic acids with similar structures and can be viewed as conformationally restricted analogues of the mammalian neurotransmitter L-glutamic acid. As the parent structure of the kainoid amino acid family, (–)-kainic acid has attracted tremendous attention because of its neuroexcitatory properties in neuropharmacology to mimic the disease states of epilepsy, Alzheimer’s disease, and Huntington’s chorea. In this thesis, a formal synthesis of (±)-kainic acid has been achieved, via a Lewis acid-catalyzed carbonyl ene cyclization as the key step, from simple starting materials 3.1 (Scheme 1). In the key step, quantitative yield of cyclization was achieved by utilizing 0.3 equivalents of Gd(OTf)3 as the catalyst in anhydrous DCM, yielding key intermediate 3.25. Moreover, the Lewis acid-catalyzed enantioselective carbonyl ene cyclization of α-keto amides (Scheme 2) represents a powerful method for the preparation of substituted pyrrolidinones. [Cu(S,S)-phenyl](SbF6)2 was found to be the most efficient chiral Lewis acid, and high yields, excellent enantioselectivity were obtained in the products. The substrate scope, reaction mechanism, diastereoselectivity and enantioselectivity of the reaction have also been systematically investigated by both experimental and computational chemistry approaches. Finally, a formal synthesis of (–)-kainic acid have been accomplished via Lewis acid-promoted PhSe group transfer radical cyclization as key the step (Scheme 3). (–)-8-Phenylmenthol was employed as a chiral auxiliary in cyclization precursor 5.13 to control the diastereoselectivity and enantioselectivity of the radical cyclization.
DegreeDoctor of Philosophy
SubjectKainic acid - Synthesis.
Dept/ProgramChemistry
Persistent Identifierhttp://hdl.handle.net/10722/181508

 

DC FieldValueLanguage
dc.contributor.advisorYang, D-
dc.contributor.authorXu, Shaobo.-
dc.contributor.author许少波.-
dc.date.accessioned2013-03-03T03:20:30Z-
dc.date.available2013-03-03T03:20:30Z-
dc.date.issued2012-
dc.identifier.citationXu, S. [许少波]. (2012). Studies towards syntheses of kainic acid. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b4979941-
dc.identifier.urihttp://hdl.handle.net/10722/181508-
dc.description.abstractKainoid amino acids are a family of none proteinogenic pyrrolidine dicarboxylic acids with similar structures and can be viewed as conformationally restricted analogues of the mammalian neurotransmitter L-glutamic acid. As the parent structure of the kainoid amino acid family, (–)-kainic acid has attracted tremendous attention because of its neuroexcitatory properties in neuropharmacology to mimic the disease states of epilepsy, Alzheimer’s disease, and Huntington’s chorea. In this thesis, a formal synthesis of (±)-kainic acid has been achieved, via a Lewis acid-catalyzed carbonyl ene cyclization as the key step, from simple starting materials 3.1 (Scheme 1). In the key step, quantitative yield of cyclization was achieved by utilizing 0.3 equivalents of Gd(OTf)3 as the catalyst in anhydrous DCM, yielding key intermediate 3.25. Moreover, the Lewis acid-catalyzed enantioselective carbonyl ene cyclization of α-keto amides (Scheme 2) represents a powerful method for the preparation of substituted pyrrolidinones. [Cu(S,S)-phenyl](SbF6)2 was found to be the most efficient chiral Lewis acid, and high yields, excellent enantioselectivity were obtained in the products. The substrate scope, reaction mechanism, diastereoselectivity and enantioselectivity of the reaction have also been systematically investigated by both experimental and computational chemistry approaches. Finally, a formal synthesis of (–)-kainic acid have been accomplished via Lewis acid-promoted PhSe group transfer radical cyclization as key the step (Scheme 3). (–)-8-Phenylmenthol was employed as a chiral auxiliary in cyclization precursor 5.13 to control the diastereoselectivity and enantioselectivity of the radical cyclization.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.source.urihttp://hub.hku.hk/bib/B49799411-
dc.subject.lcshKainic acid - Synthesis.-
dc.titleStudies towards syntheses of kainic acid-
dc.typePG_Thesis-
dc.identifier.hkulb4979941-
dc.description.thesisnameDoctor of Philosophy-
dc.description.thesislevelDoctoral-
dc.description.thesisdisciplineChemistry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b4979941-
dc.date.hkucongregation2013-

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