Enantioselective Total Synthesis of Dideoxyverticillin

A synthesis of the alkaloid dideoxyverticillin should be performed. The main issue of the planned synthesis is the stereoselective construction of the disulfide bridges of the target molecule. A reaction sequence of this kind has only been performed on much simpler molecules previously and was not stereoselective. It is intended that a stereoselective synthesis of the alkaloid dideoxyverticillin will be completed during a post- doctoral stay in the research group of Prof. Larry E. Overman. Many members of this class of compounds are distinguished by high cytotoxicity as well as antibacterial activity. A synthesis of a typical member of this class of compounds therefore is not only of academic but also of medicinal and pharmaceutical interest. The first steps of the reaction sequence make use of procedures developed by Overman et al. during the syntheses of related compounds. Improvements in the current procedures are envisioned by the use of a novel catalyst. The planned reaction sequence involves technology developed during the syntheses of simpler, structurally related compounds. The most important structural feature of the target molecule, the disulfide bridges, should be introduced in the final steps of the sequence. A combination of known procedures, used for much simpler compounds, and the experience of the Overman group with the sterically demanding carbon skeleton of the target molecule, should allow a stereoselective synthesis of the disulfide bridges. After the successful synthesis of dideoxyverticillin studies towards the syntheses of chaetocin and dihydroxychaetocin will be undertaken.