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RESEARCH PROJECT Dottorato di ricerca-XX ciclo DOTTORANDO: PAPANDREA GIOVANNI TUTOR: Prof. PONTICELLI FABIO TITLE: Design and Stereoselective Synthesis of Highly Substituted Cyclohexenes/Cyclohexanes and Cyclopentenes/Cyclopentanes Initial scientific support: A number of reports in the literature lead to design potential drugs in which the cyclopentene/cyclopentane and cyclohexene/cyclohexane rings served as scaffold for substituents (carboxilate, guanidine, acetamido, azido, alkyl, hydroxyl group, ….). We find some of these compound in neuromidase inhibitors1 (1 and 2), in ligands for the FP-receptor2 (3), in adenylyl cyclase inhibitors3 (4), in antiviral agents4 (5). CO2H CO2H O HO CO2H N H H NH2 HN X O NH2 HN NHCOCH3 1 HO OH 3 2 NH2 x= N, S O N N N N N N HN N NH2 OH OH 4 5 CO2CH3 Research target : Formation and transformations of bonds, interconversion of functional groups of easily starting materials into complex building blocks is very important in Organic Chemistry. Generally, in this work the starting materials are cyclic 1,3-dienes (cyclopentadienes and cyclohexadienes) on which different functional groups will be introduced. However, the intricate access to functionalized cycloalkenes often is the major drawback to a practical use of these reactions. One solution to by pass this problem is based on Diels-Alder reactions, in fact several research groups have elegantly demonstrated the synthetic versatility of numerous organic system involving DielsAlder chemistry and many of them have just been exploited for the synthesis of cyclopentensulfonic amino acid with good yield. Another utility of Diels-Alder approach is the high degree of regio and stereo selectivity, due to the concerted mechanism. As a conseguence, it is well known that after the syn introduction of the first functional group by Diels-Alder cycloaddition, there is a sure dependence upon the future stereochemistry of the next substituents around the cyclopentene/cyclohexene ring tether, which will be continued to probe through the synthesis of all possible stereoisomers. In fact, this study will be focused not only on the rigidity of the synthetic tether, but also it will take in to account the spatial aspects of molecules within the tether, having in mind the regio and stereoselective synthesis of all possible isomers because the biological properties of organic molecules largely depend on their stereochemistry. Bibliography: 1. BioCryst Pharmaceutical, J. Med. Chem., 2004, 47, 1919-1929. 2. Procter and Gamble Pharmaceutical, J. Med. Chem., 2000, 43, 945-952. 3. Danilel E. Levy et al., J. Med. Chem., 2003, 46, 2177-2186. 1. Jing Wang et al., J. Med. Chem., 2000, 43, 736-745.