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Synthesis of nicotine derivatives using solid supported reagents

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Research objectives and content The nicotine is a natural alkaloid with high complex physiological activity. It is widely accepted that nicotine and its agonists could be used for the treatment of Alzheimer'disease, Parkinson's disease and as ansyolitic, antidepressive and schizophrenic therapeutic agents. The low availability of compounds structurally related to nicotine is a serious obstacle for structure activity relationships. Therefore, a novel total synthesis based on the use of polymeric supported reagents should allow the preparation of a large number of similar nicotine derivatives in a automatic fashion. For example, the polymer supported perruthenate (PSP), prepared by the methodology develop by the group of Prof. S.V. Ley, already successful applied in the synthesis of chemical libraries of other natural products. Based on these results we propose here the use of this reagents in two steps of a synthesis of nicotine derivatives based on solid supported reagents. Training content (objective, benefit and expected impact) I consider that the University of Cambridge it is now one of the most important European research centers in Organic Chemistry. During my training stay there, under the supervision of Prof. Steven V. Ley, I expect to improve my knowledge and experience in Synthetic Organic Chemistry: At the moment I have carried out research directed to methodologic aspects and would gain very much by working on a total synthesis project. Links with industry / industrial relevance (22) The understanding of the structure/activity relationship of nicotine and their af antidepressive properties are of great relevance for medicine and the pharmaceutical industry.

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University of Cambridge
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Lensfield Road
CB2 1EW Cambridge
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