The Application of Pericyclic, Photolytic, Chemoenzymatic and Cross-coupling Techniques to the Synthesis of Biologically Active Natural Products and Related Structures
Creators: name: Yan, Qiao
Publisher: name: The Australian National University
Year: 2017
Subjects: Rezishanone C
Photochemical Rearrangements
Carbazole
Carboline

description: 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.