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Total synthesis of spongistatin 1

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Spongistatin 1, also known as Aftohyrtin A, is currently one of the most exciting and sought after targets among synthetic organic chemists. It belongs to a family of extraordinary potent antitumor compounds that have been isolated from marine sponges. Spongistatin 1 appears to be the most potent antimitotic cancer cell growth inhibitor ever discovered. However, the natural supply of the product is very limited and therefore, a chemical synthesis is urgently required in order to dispose of sufficient amount of the compound to carry out further biological testing. Such synthesis should be both convergent and versatile, leading itself to the easy preparation of structural analogues of the spongistatins. This will in turn allow the structure-activity relationships of the molecule to be probed and may lead to a structurally simpler but equally powerful antitumor agent ameanable to large-scale production. Existing and new synthetic methodology will be challenged by this highly complex molecule synthesis. Moreover, novel methods are likely to be discovered to overcome unforeseen problems. These will benefit the synthetic community as a whole as we gain insights into how to synthesize molecules with ever increasing complexity. Research at Cambridge University is universally recognized as being world class by any standard. The Department of Chemistry is one of the largest and most active in Europe. It has demonstrated over many years that it produces some of the best students who go into industry and rise to high positions within those companies. The skill base available is excellent as one of the top rated institutions in the world and this department provides outstanding training of Ph. D. and postdoctoral students many of whom find their way into the chemical industry particularly the pharmaceutical and agrochemical sectors. In this context, I expect to improve my knowledge and experience in synthetic organic chemistry and also hope that I will learn new experimental and structural determination techniques and I will be involved in the general activities of the Department. My contribution to Prof. Ley's research group will be based on my experience in organic and organometallic chemistry, as well as NMR elucidation.

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