Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules ....Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules being sought in the development of new therapeutic agents and/or materials. The combined application of molecular biological, microbiological and chemical synthesis techniques in a concerted manner in the one location will lead to a raft of new opportunities for the biotech and pharmaceutical industries in Australia.Read moreRead less
Eradicating bacterial biofilms with nitroxide-antimicrobial hybrids. This project aims to develop new antimicrobials to address the rise of drug-resistant infections and resilient bacterial communities called biofilms. We aim to break new ground in our fundamental knowledge of antimicrobial mechanisms and exploit this understanding by fusing cellular/molecular microbiology and synthetic chemistry approaches. We seek to gain an in-depth understanding of how nitroxides induce bacterial biofilm dis ....Eradicating bacterial biofilms with nitroxide-antimicrobial hybrids. This project aims to develop new antimicrobials to address the rise of drug-resistant infections and resilient bacterial communities called biofilms. We aim to break new ground in our fundamental knowledge of antimicrobial mechanisms and exploit this understanding by fusing cellular/molecular microbiology and synthetic chemistry approaches. We seek to gain an in-depth understanding of how nitroxides induce bacterial biofilm dispersal, which is critical for the discovery of anti-biofilm molecules that do not fail due to resistance development. These breakthroughs should induce a step-change in our ability to reduce the occurrence of biofilm-related infection in fields ranging from medical and veterinary to biotechnology and agriculture.Read moreRead less
pH Switching of Radical Reactivity and Orbital Conversion. Radicals are reactive species that have an unpaired electron, which is usually located in the highest occupied orbital. This proposal uses a combination of theory and experiment to design a new class of radical anions whose unpaired electron is not the highest occupied orbital, and whose electronic configuration reverts to the normal aufbau configuration upon protonation. These special radical anions will display unprecedented radical st ....pH Switching of Radical Reactivity and Orbital Conversion. Radicals are reactive species that have an unpaired electron, which is usually located in the highest occupied orbital. This proposal uses a combination of theory and experiment to design a new class of radical anions whose unpaired electron is not the highest occupied orbital, and whose electronic configuration reverts to the normal aufbau configuration upon protonation. These special radical anions will display unprecedented radical stability that is pH switchable, as well as ferromagnetism and conductivity upon oxidation. This project will exploit these unusual properties in the design of pH-switchable protecting groups for radicals for synthesis and polymerisation, and determine their role in oxidative stress and enzyme kinetics.Read moreRead less
New Horizons in Diels-Alder Chemistry. Using a unique joint experimental-computational approach, we will develop reliable ways to predict the outcome of one of the most important chemical reactions. Practical applications of these new predictive tools will be developed involving powerful new versions of the reaction. Several different classes of biologically active natural products will be prepared including molecules with antitumor and antiretroviral activities. Libraries of structurally-relate ....New Horizons in Diels-Alder Chemistry. Using a unique joint experimental-computational approach, we will develop reliable ways to predict the outcome of one of the most important chemical reactions. Practical applications of these new predictive tools will be developed involving powerful new versions of the reaction. Several different classes of biologically active natural products will be prepared including molecules with antitumor and antiretroviral activities. Libraries of structurally-related analogues of natural compounds will be synthesised for biological evaluation.Read moreRead less
Enhanced Synthetic Efficiency For Molecular Complexity and Diversity. This project aims to introduce new, broad-spectrum strategies that permit more efficient and selective ways to access complex organic molecules. The approach involves maximising the molecule-building potential of some of the smallest accessible molecular building blocks. Significant outcomes expected from this work include much shorter chemical syntheses of important organic substances and much improved, broad scope synthetic ....Enhanced Synthetic Efficiency For Molecular Complexity and Diversity. This project aims to introduce new, broad-spectrum strategies that permit more efficient and selective ways to access complex organic molecules. The approach involves maximising the molecule-building potential of some of the smallest accessible molecular building blocks. Significant outcomes expected from this work include much shorter chemical syntheses of important organic substances and much improved, broad scope synthetic methods. The concepts introduced by this work aims to benefit industry and manufacturing by introducing more efficient methods for fine chemical manufacture, while simultaneously lowering energy use and producing less waste.Read moreRead less
Exploitation of unusual patterns of reactivity of peptides towards radicals. Life depends on free radical reactions of peptides and proteins but, for these compounds to exist, these must be inherently resistant to radicals. This project aims to combine state-of-the-art experiment and theoretical computations to build a detailed picture of peptide and protein radical reactivity, in order to explain this paradox and resolve ambiguities regarding processes through which radical damage to peptides o ....Exploitation of unusual patterns of reactivity of peptides towards radicals. Life depends on free radical reactions of peptides and proteins but, for these compounds to exist, these must be inherently resistant to radicals. This project aims to combine state-of-the-art experiment and theoretical computations to build a detailed picture of peptide and protein radical reactivity, in order to explain this paradox and resolve ambiguities regarding processes through which radical damage to peptides occurs and is repaired. The project also aims to critically evaluate the basic concept of the fidelity of amino acid incorporation during protein biosynthesis. The results of this project could underpin the development of new strategies and therapeutics to treat human diseases, and new materials and synthetic methods to increase the utility of peptides in biotechnology.Read moreRead less
Biomimetic Synthesis of Dimeric Natural Products. The aim of this research is to use nature as a source of inspiration and direction to improve and develop synthetic organic chemistry. Through targeted total syntheses this project will investigate and learn about the highly sophisticated way nature utilises dimerizations to rapidly generate molecular complexity. This project will demonstrate the power of this biomimetic strategy by synthesising a wide variety of complex dimeric natural products ....Biomimetic Synthesis of Dimeric Natural Products. The aim of this research is to use nature as a source of inspiration and direction to improve and develop synthetic organic chemistry. Through targeted total syntheses this project will investigate and learn about the highly sophisticated way nature utilises dimerizations to rapidly generate molecular complexity. This project will demonstrate the power of this biomimetic strategy by synthesising a wide variety of complex dimeric natural products including phenylethanoids, alkaloids, lignans, terpenes and coumarins. The expected outcome will be uniquely efficient synthetic strategies that significantly surpass all previous approaches and new synthetic methodology that will be of broad use in organic synthesis.Read moreRead less
New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bact ....New Protocols for the Chemical Synthesis of Biologically Relevant Systems. Enzyme- and metal-catalysed processes will be developed and exploited for the purpose of establishing concise syntheses of biologically active and otherwise inaccessible natural products and their analogues. The range of structures to be targeted is structurally diverse and these have the potential to act as agrochemicals and/or as therapeutic agents for the treatment of a range of disease states in mammals including bacterial and viral infections, neuro-degenerative conditions and impaired cognitive function. Anti-angiogenic compounds that control otherwise unregulated cellular growth may also arise from these studies. The generation of new, homochiral metabolites for use in chemoenzymatic synthesis should also emerge from this project.Read moreRead less
Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically ....Harnessing strain for chemical synthesis: The cyclopropane angle. This project aims to develop new reaction pathways of cyclopropanes, the smallest and most strained monocyclic ring systems, but which are also stable and easily prepared. Cyclopropanes have unique capacities to serve as highly effective building blocks in the synthesis of a wide range of otherwise difficult to access and biologically active molecular frameworks. This project will use cyclopropanes to rapidly assemble biologically active systems, especially pharmaceutically or agrochemically valuable natural products and relevant analogues.Read moreRead less
Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules ....Generation of Novel Fermentation Products and their Exploitation in the Synthesis of Biologically Active Organic Compounds with Therapeutic Potential. Collections of new micro-organisms and their metabolites suitable for use in the chemical synthesis programs will emerge from the proposed research. This will provide a potentially highly-valuable national resource that could serve the needs of many laboratories around Australia by allowing them to establish more direct routes to target molecules being sought in the development of new therapeutic agents and/or materials. The combined application of molecular biological, microbiological and chemical synthesis techniques in a concerted manner in the one location will lead to a raft of new opportunities for the biotech and pharmaceutical industries in Australia. Read moreRead less