Browsing by Subject "Diels-Alder"
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Item Access to Indoles via Diels-Alder reactions of vinylpyrroles.(2009-05) Lanzatella, Nicholas PeterThe indole moiety is extremely common in biologically active natural and un-natural products. Exploration and discovery of methods for generating the indole nucleus provides new and potentially more efficient options for synthetic approaches to indole-containing compounds. Vinylpyrroles have electron-rich pi systems and perform well as dienes in normal electron-demand Diels-Alder reactions with sufficiently electron-deficient dienophiles. The resulting substituted dihydro- or tetrahydroindoles are dehydrogenated to the corresponding indoles. Tosylation of pyrrole promotes acylation under Friedel-Crafts conditions at the difficult-to-access 3-position, which after reduction and dehydration gives 3-vinylpyrroles. These partially deactivated stable crystalline pyrroles have sufficient electron density to provide a novel and advantageous [4+2] cycloaddition route to indoles. Due to the high reactivity and consequent tendency of pyrroles to undergo undesired side-reactions, protecting groups are often desirable in pyrrole chemistry. However, the requirement for a sufficiently electron-rich diene, along with the sensitive nature of pyrroles, restricts the use of traditional blocking groups. Methylthio-protected 2-vinylpyrroles are shown to act as effective dienes in Diels-Alder reactions, demonstrating new blocking group techniques for chemistry involving sensitive pyrroles.Item Spontaneity to serendipity: from an enediyne core biosynthetic hypothesis to the hexadehydro-Diels-Alder reaction(2014-08) Woods, Brian PatrickEnediyne containing natural products have promising potential as cancer therapeutics due to their unique molecular architecture. The (Z)-1,5-diyn-3-ene subunit in the enediyne core can undergo cycloaromatization to yield a diradical capable of scission of the DNA double helix. While the biological mechanism of action is well established, almost nothing is known about the biosynthesis of the enediyne core. Specifically, researchers have been unable to identify a cyclase enzyme capable of ring-closing acyclic precursors. In the case of 9-membered enediynes, we propose that the bicyclic enediyne core is formed biosynthetically via spontaneous (i.e. non-enzymatic) cyclization from an acyclic precursor. In the course of examining this hypothesis, we serendipitously encountered a [4+2] cyclization between a diyne and an alkyne. The product of such a cycloaddition is one of the oldest and most interesting reactive intermediates in organic chemistry, o-benzyne. This process, which we have termed a hexadehydro-Diels-Alder (HDDA) reaction, has remained almost entirely unexploited until now. The strategy unites an entirely atom-economical, thermal generation of arynes with their in situ elaboration into a diverse set of polysubstituted benzenoids. HDDA precursor triynes cycloisomerize in a very exergonic fashion to produce complex benzyne intermediates, which are trapped with a variety of inter- and intra-molecular functionalities in an efficient and selective manner. The byproduct-free environment in which the benzynes are generated allows for new trapping reactions to be discovered and for mechanistic pathways to be interrogated and elucidated.Item A synthesis of the octalin core of integramycin, isolation of alkaloids from Amazonian plants, and polyols from renewable resources(2012-07) Emond, Susanna JeanThis document is a presentation and discussion on three projects in three parts. Part One is a detailed summary of organic chemistry efforts in the synthesis of a model of the natural product integramycin. This concludes six years of work on various synthetic routes and analysis of spontaneous Diels-Alder chemistry. The goal was to probe part of our group's larger biosynthetic hypothesis concerning spontaneity in the biosynthesis of polyketides. Part Two summarizes the natural products chemistry that I performed while being supported by a UMN Graduate School Interdisciplinary Doctoral Fellowship. This was a year-long effort (academic year 2010-2011) in identifying the main chemical components of various plant samples from the Amazon. The goal was to isolate new natural products, elucidate their novel structures, and study the biological activity of these constituents. Part Three is a summary of the advances I made as a polymer chemist through the support of the UMN Center for Sustainable Polymers. This work began in the summer of 2010 and includes the investigation of both soybean oil and natural terpenoids as precursors to polyols for use in polyurethanes. The goal was to prepare sustainable polyurethanes for flexible foam applications.Item Toward a total synthesis of Englerin A(2014-12) Goebel, Erik S.Englerin A is a guiane sesquiterpenoid isolated from the spurred potato-bush Phyllanthus engleri that has shown potent and selective activity against renal cancer cell lines. Our approach to the synthesis of englerin A features a Diels-Alder reaction between an axially chiral allene and a 3-siloxyfuran. We have found the oxabicyclo[2.2.1]heptane framework to be a sterically formidable structure and have discovered a novel decomposition pathway of acetyl-oxabicyclo[2.2.1]heptanes to 3(2H)-furanones.