Organic Catalysts Incorporating Catalytic Triads

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New chemical compounds which exhibit potentially useful biological activity / be it toxicity against cancer cells or antibiotic properties, are identified on an almost daily basis in both natural organisms and collections of man-made compounds. Subsequently, closely related structures are often examined to determine which parts of these molecules are responsible for the beneficial effects. In the course of this drug development process, thousands of molecules may be synthesized in pursuit of just one that has the desirable medical effects, is readily absorbed by the body and is non-toxic. Synthetic chemistry is therefore of fundamental importance at every stage. Meanwhile, the many recent advances in the biological sciences (such as the completion of the human genome sequence) have increased the rate at which potential targets for new disease treatments can be identified. As a consequence, the demand for drug molecules directed towards these new targets is increasing rapidly, and efficient, effective methods of chemical synthesis, particularly those which result in the construction of structural features common in drugs, are of paramount importance.The proposed research focuses on the development of new 'catalytic' methods for chemical synthesis, in which only a small quantity of chemical reagent (a 'catalyst') is required in order to convert much larger quantities of starting materials into products. The catalyst design will be inspired by natural enzymes, which are able to carry out countless chemical reactions in a catalytic fashion. We will also take inspiration from existing chemical methods for carrying out the reactions under investigation, adapting them for use in a catalytic manner. The chemical reactions which we will concentrate on have been identified in a number of recent documents (published by representatives of the global pharmaceutical industry, the American Chemical Society and the UK government research councils) as being of fundamental importance in the synthesis of drug molecules. These documents noted that there is currently a lack of efficient and environmentally-friendly chemical methods for carrying out these processes and that academic research directed towards developing such methods is urgently required.For example, amide bonds are found in more than 25% of existing drug molecules, as well as in naturally occurring molecules such as proteins, and their formation is amongst the most common of all transformations in organic chemistry. There are, however, currently no effective catalytic methods for forming these bonds. Indeed, the existing, non-catalytic technologies often require large quantities of chemical reagents that are expensive and/or toxic. We will aim to develop simple organic (carbon-based) molecules as catalysts for this reaction which will act by 'holding onto' and 'organising' the starting materials, and directing them to react together to form the amide bond. The only chemical by-products of this new process will be water and the small quantity of the catalyst itself, which can be recovered and recycled. Such a catalyst would have immediate and far-reaching application in many avenues of scientific research. The concepts outlined in this work will also be applied to the development of catalysts for many other important chemical reactions.These new catalysts will have widespread application in the synthesis of molecules for use as new drugs and agrochemicals and in the study of living cell processes, and as such will be beneficial to scientists working in many areas of chemistry, medicine and biology.