Total synthesis of 11-membered cytochalasins as new molecular tools

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Cytochalasine are members of a group of natural products, which effect a variety of biological activities based on one common backbone. The observation that natural products can address different biological targets using one common backbone can also be made for other natural products. A systematical deconvolution of this phenomenon and the identification of the factors controlling specificity can be of important value for the field of natural products as well as for medicinal chemistry. For the identification of biological targets and the description of factors that result in addressing these targets synthetic access is essential. For six members of the group of 11-membered Cytochalasins synthetic access will be secured with this project and provided for biological investigations. The syntheses propose a late-stage incorporation of amino side chains and thus enable the rapid synthesis of a variety of derivatives. Besides the incorporation of side chains of proteinogenic amino acids, fluorescente aromatic compounds can be incorporated as well. These compounds can be used for target identification and cell localization. The syntheses use two cis or trans-substituted side chains which synthesis was established in our group. For the macro cyclization a Ramberg-Bäcklund reaction will be used and thus establish an unprecedented strategy for cytochalasin synthesis which will enhance cyclisation efficiency.