Download or read book Studies on the Total Synthesis of Some Biologically Active Natural Products written by Yiwen Zhang and published by . This book was released on 2018 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The body of this thesis is comprised of four scientific journal articles and a patent. It is preceded by an overview that contextualizes all of this submitted/published work. The first major part of this thesis is comprised of Publication 1. This is a review concerned with the chemical syntheses of the cochliomycins, including congener A, and certain related resorcylic acid lactones (RALs). pecifically, Publication 1 reviews the recently published literature on the cochliomycins and related, co-occurring RALs and is accompanied by a brief commentary on the source organisms and certain of their biological properties. It serves to contextualize some of the author's other published research incorporated in the thesis. The second major part of this thesis is comprised of Publication 2. This details work concerned with establishing the true structure of the marine-derived RAL neocosmosin A. Specifically, the structure, A, originally assigned to neocosmosin A was synthesized with the key steps involving olefin-cross metathesis, ring-closing metathesis, palladium- catalyzed Meinwald rearrangement and Mitsunobu esterification reactions. A late-stage and simple modification to the reaction sequence also provided the enantiomer B that, in fact, represents the true structure of the natural product. The third major part of this thesis is comprised of Publication 3. This details the development of modular total syntheses of the marine-derived alkaloids discoipyrroles A and B. Specifically, the intermediates C and D (see below) were prepared from (parent) pyrrole using Ullmann-Goldberg and Suzuki-Miyaura cross-coupling, Vilsmeier-Haack formylation, electrophilic bromination, and Wittig olefination reactions as key steps. A late stage MoOPH-mediated oxidative cyclization reaction was then employed to assemble the novel heterobicyclic core of the target discoipyrroles. The fourth major part of this thesis is comprised of Publication 4. This details the first total synthesis of the most structurally complex member of the small family of marine- derived discoipyrroles, namely congener D. This synthesis, which used methodology developed during the course of the aforementioned syntheses of the discoipyrroles A and B, involved, as key steps, the MoOPH-mediated oxidative cyclization of precursor E and this was followed by conjugate addition and redox processes. The fifth and final part of this thesis is comprised of Publication 5. This patent details inventions related to methods for preparing a variety of discoipyrrole-like compounds and novel analogues, as well as pharmaceutical compositions comprising these compounds and their possible use in therapeutic settings. For example, compound F, which incorporates a discoipyrrole-like core structure, was synthesized in four steps from indole and involving the aforementioned MoOPH-mediated oxidative cyclization as one of the key processes. The Appendices to the thesis are comprised of a series of reports arising from single-crystal X-ray analyses of certain key compounds synthesized by the author. Drs Jas Ward, Paul Carr or Anthony Willis, members of the Research School of Chemistry's Crystallographic Analysis Unit, conducted these analyses.

Download or read book The Application of Pericyclic Photolytic Chemoenzymatic and Cross coupling Techniques to the Synthesis of Biologically Active Natural Products and Related Structures written by Qiao Yan and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The body of this thesis is comprised of four scientific articles and is preceded by an overview that contextualises all of this submitted/published work. The first major part of this thesis is comprised of Publication 1. This details work concerned with establishing the true structure of the sorbicillinoid-derived isolate rezishanone C by total synthesis. Specifically, the enantiomer of what proved to be the true structure of the sorbicillinoid rezishanone C (sorbivinetone) was synthesized from the homochiral cis-1,2-dihydrocatechol that is itself generated through the whole-cell biotransformation of toluene. These studies and dispersion-corrected DFT calculations support the proposal that rezishanone C is an artefact of the isolation process and arises through a Diels-Alder cycloaddition reaction between ethyl vinyl ether and sorbicillinol. The second major part of the thesis is comprised of Publication 2. This is concerned with the synthesis and photochemical rearrangements of enantiomerically pure, polysubstituted and, in some cases, variously annulated bicyclo[2.2.2]octenones. Specifically, then, a series of bicyclo[2.2.2]octenones has been prepared by engaging the enzymatically-derived and enantiomerically pure cis-1,2-dihydrocatechol in either inter- or intra-molecular Diels-Alder cycloaddition reactions with various dienophiles. These polycyclic adducts or simple derivatives thereof were shown to readily participate in both photochemically promoted 1,3-acyl migration and oxa-di-pi-methane rearrangement processes to give corresponding products. The third major part of the thesis is comprised of Publication 3. This details the establishment of a palladium-catalyzed Ullmann cross-coupling/reductive cyclization route to the carbazole natural products 3-methyl-9H-carbazole, glycoborine, glycozoline, clausazoline K, mukonine and karapinchamine A. These were prepared by reductive cyclisation of the relevant 2-arylcyclohex-2-en-1-one to the corresponding tetrahydrocarbazole and dehydrogenation of this to give the target carbazole. Compounds of 2-arylcyclohex-2-en-1-one were themselves prepared using a palladium-catalyzed Ullmann cross-coupling reaction that served to link the appropriate 2-iodocyclohex-2-en-1-one and o-halonitrobenzene. The fourth and final part of the thesis is comprised of Publication 4. This details a unified approach to the isomeric alpha-, beta-, gamma- and delta-carbolines via their 6,7,8,9-tetrahydro counterparts. Specifically, then, a cross-coupling/reductive cyclisation protocol has been employed in preparing all four carbolines. So, for example, the 2-nitropyridine derivative, which is readily generated through an efficient palladium-catalyzed Ullmann cross-coupling reaction, is reductively cyclized under conventional conditions to give 6,7,8,9-tetrahydro-alpha-carboline that is itself readily aromatized to give alpha-carboline.