Browsing by Subject "Quebrachamine"

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    Development of Stereoselective Cyanoamidation Reactions and Their Application to Natural Product Total Synthesis
    (2019-12) Eastwood, Matthew
    Chapter 1. A survey of the literature to date on the palladium-catalyzed cyanoamidation reaction, both in terms of synthesis and mechanism. Details of work expanding the substrate scope of diastereoselective alkene cyanoamidation, as well as studies toward the removal of the chiral directing group, which necessitated development of a method for chemoselective reduction of hindered lactams in the presence of nitriles. Chapter 2. A review of the literature regarding the synthesis of asymmetric Aspidosperma alkaloids quebrachamine and eburnamonine. Approaches to scalemic material by a wide variety of routes. Chapter 3. A discussion of work towards an enantioselective cyanoamidation of a highly functionalized aliphatic-tethered alkene towards the synthesis of Aspidosperma alkaloids is presented. Efforts toward the functionalization of cyanoamidation products towards quebrachamine, including attempts at forming the alkaloid’s nine-membered ring and the application of diastereoselective cyanoamidation, are discussed. A successful total synthesis of (+)-eburnamonine in four steps from the scalemic cyanoamidation product. Chapter 4. A review of the literature published to date on the synthesis of madangamine alkaloids, including approaches to the diazatricyclic core, macrocyclic rings, and completed total syntheses of various members of the madangamine family. Chapter 5. A discussion of the variety of approaches undertaken towards the synthesis of a di(cyanoformamide) thought to be a viable substrate for a cyanoamidation-based C–C bond activation cascade for making the madangamine core. Details of the development of said cascade reaction and successful synthesis of a madangamine core derivative.
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    Studies of Intramolecular Cyanoamidation with Alkenes and Application Toward the Total Synthesis of Natural Products
    (2017-10) Otte, Sadie
    Chapter One. A brief discussion of the relevant background in intramolecular cyanoamidation. Examples from successive methodology studies are given. The proposed mechanism and published mechanistic experiments are presented, along with its applications in the synthesis of complex molecules. Chapter Two. A summary of the design, discovery, and optimization of the diastereoselective intramolecular cyanoamidation reaction is presented. Significant findings are discussed along with a preliminary substrate scope. A detailed description of our attempts to cleave the chiral directing group is given. Chapter Three. An overview of the Aspidosperma alkaloid family with an emphasis on quebrachamine is presented. A discussion is given of the isolation, biological activity, and previous total syntheses of quebrachamine. Strategies for the synthesis of the all–carbon quaternary center and formation of the nine–membered ring are specified. Chapter Four. A novel strategy for the total synthesis of quebrachamine via intramolecular cyanoamidation is proposed. Three routes to the key cyanoformamide intermediate are presented. Optimization of the intramolecular cyanoamidation is described along with reproducibility studies. Progress toward the final ring closure between indole and nitrile groups via one– and two–step methods is discussed, along with future work. Chapter Five. The application of a serendipitously discovered Bischler–Napieralski-type reaction toward the total synthesis of eburnamonine is proposed. Optimization of the reaction is discussed along with attempts to grow high-quality crystals of the product. Subsequent efforts to hydrogenate the iminium ion product are presented.