Studies Towards the Total Synthesis of Imidazole-containing Natural Products

Download or read book Studies Towards the Total Synthesis of Imidazole-containing Natural Products written by Lawton Anthony II Seal and published by . This book was released on 2019 with total page 114 pages. Available in PDF, EPUB and Kindle. Book excerpt: Nature has inspired man in all aspects of life, chemistry included. The first antibiotic ever discovered came from nature, and since then, chemists have been probing nature for insights to guide drug discovery and development. Alkaloids are a class of naturally occurring molecules which contain nitrogen atoms and can be found in all forms of life. Imidazole is common structural unit found in many natural molecules, from the simple amino acid histamine to more complex structures like the marine sponge derived alkaloid palau'amine. Many imidazole-containing natural products are biologically active, such as inhibiting the growth of tumors, possessing antibacterial properties, and influencing signaling pathways of cells like an inflammatory response. Access to large quantities of these molecules would aid medical science in drug discovery and design, potentially impacting the overall quality of life for all. It is therefore essential for the chemical community to pursue the synthesis of natural products not only to gain more knowledge in the overall science, allowing for better isolation,characterization, and synthesis of molecules, but also to better the quality of life and health as a whole.Chapter 1 of this dissertation describes the isolation and characterization of spiroleucettadine and terrazoanthines A-C. It further describes, in detail, the unsuccessful attempts to synthesis spiroleucettadine, which prompted its structural revision, and the only reported synthesis of the revised structure.Chapter 2 focuses on our approach to the total synthesis of spiroleucettadine. Initially our strategy centered on employing a novel reaction discovered in our lab to help facilitate the construction of the spirocyclic center. However, we later found this route to not be viable,leading to a significant revision in our strategy.In chapter 3 describe our approach to total synthesis of terrazoanthines A-C. Besides its purification and structural assignment,there are no reports pertaining to this molecule in the literature. Of the 3 molecules, only one of them possesses multiple stereochemical centers. However, upon further examination of the core structure we proposed a concise synthetic route leading to not only all 3 molecule, all possible stereoisomers through the construction of a key symmetric intermediate.In chapter 4 we discuss the oxidative chemistry of tetrahydrobenzimidazole. The two oxidants used were dimethyldioxarine and oxaziridine. The results show the choice of oxidant, N-protecting group,and the functionalization at the C2-position can greatly affect the outcome of the reactions, leading to additions, cyclizations, and ring openings.