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The Global ETD Search service is a free service for researchers
to find electronic theses and dissertations. This service is
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Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 1 to 2 of 2 (0.047 seconds)Spelling suggestions: "subject:"benzofuranones"" "subject:"benzofurane""
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Total syntheses of sanggenon-type natural products and rearrangements of 3-substituted flavone ethersXiong, Yuan 22 January 2016 (has links)
An efficient approach to the hydrobenzofuro[3,2-b]chromenone core of sanggenon-type natural products has been developed. The key transformation involves a protecting group-free double rearrangement of a bis-allyloxyflavone ether substrate. A sequence involving asymmetric 3-allyl rearrangement followed by aromatic Claisen rearrangement has been established for the asymmetric synthesis of the hydrobenzofuro[3,2-b]chromenone core structure. This methodology has been successfully applied to asymmetric syntheses of both sanggenol F and sanggenon A.
Efficient chiral, racemic syntheses for sanggenons C and O have been achieved. The key transformation entails a biomimetic Diels-Alder cycloaddition between a flavonoid diene and a 2'-hydroxychalcone. The flavonoid diene was produced from a protected flavonoid chromene via isomerization.
Metal-catalyzed alkynyl Claisen (Saucy-Marbet) rearrangements of 3-alkynyl flavone ethers have been evaluated, and a 1,2-acyl migration cascade which afforded novel furanyl benzofuranone scaffolds was discovered. Mechanistic studies have revealed that the rearrangement is likely initiated by 5-endo enyne cyclization to a platinum-containing spiro-oxocarbenium intermediate, which may be intercepted by methanol to produce a spirodihydrofuran or further rearranged to afford allenyl chromanediones and benzofuranones at higher reaction temperature. Lewis acid-catalyzed [1,3]-rearrangements of 3-aryl substituted flavone ethers have also been developed.
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Homology modeling and structural analysis of the antipsychotic drugs receptoromeLópez Muñoz, Laura 22 June 2010 (has links)
Classically it was assumed that the compounds with therapeutic effect exert their action interacting with a single receptor. Nowadays it is widely recognized that the pharmacological effect of most drugs is more complex and involves a set of receptors, some associated to their positive effects and some others to the side effects and toxicity. Antipsychotic drugs are an example of effective compounds characterized by a complex pharmacological profile binding to several receptors (mainly G protein-coupled-receptors, GPCR). In this work we will present a detailed study of known antipsychotic drugs and the receptors potentially involved in their binding profile, in order to understand the molecular mechanisms of the antipsychotic pharmacologic effects.The study started with obtaining homology models for all the receptors putatively involved in the antipsychotic drugs receptorome, suitable for building consistent drug-receptor complexes. These complexes were structurally analyzed and compared using multivariate statistical methods, which in turn allowed the identification of the relationship between the pharmacological properties of the antipsychotic drugs and the structural differences in the receptor targets. The results can be exploited for the design of safer and more effective antipsychotic drugs with an optimum binding profile. / Tradicionalmente se asumía que los fármacos terapéuticamente efectivos actuaban interaccionando con un único receptor. Actualmente está ampliamente reconocido que el efecto farmacológico de la mayoría de los fármacos es más complejo y abarca a un conjunto de receptores, algunos asociados a los efectos terapéuticos y otros a los secundarios y toxicidad. Los fármacos antipsicóticos son un ejemplo de compuestos eficaces que se caracterizan por unirse a varios receptores simultáneamente (principalmente a receptores unidos a proteína G, GPCR). El trabajo de la presente tesis se ha centrado en el estudio de los mecanismos moleculares que determinan el perfil de afinidad de unión por múltiples receptores de los fármacos antipsicóticos.En primer lugar se construyeron modelos de homología para todos los receptores potencialmente implicados en la actividad farmacológica de dichos fármacos, usando una metodología adecuada para construir complejos fármaco-receptor consistentes. La estructura de estos complejos fue analizada y se llevó a cabo una comparación mediante métodos estadísticos multivariantes, que permitió la identificación de asociaciones entre la actividad farmacológica de los fármacos antipsicóticos y diferencias estructurales de los receptores diana. Los resultados obtenidos tienen interés para ser explotados en el diseño de fármacos antipsicóticos con un perfil farmacológico óptimo, más seguros y eficaces.
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