An asymmetric total synthesis of the marine alkaloid nakadomarin A is proposed. This natural product exhibits a broad range of biological activities, including cytotoxicity against lymphoma cells, inhibition of cyclin dependent kinase 4, antifungal activity, and antibacterial activity. The proposed synthetic strategy includes a key diastereoselective and regioselective azomethine-ylide [1,3]-dipolar cycloaddition to establish three of the four stereocenters in the molecule. The synthesis also includes the use of transition metal catalysis for subsequent carbon-carbon bond forming reactions. Specifically, a tandem palladium-catalyzed furan synthesis and intramolecular Hock reaction are proposed for construction of the ABCDE pentacyclic core. Additionally, ring-closing metathesis reactions will be used to prepare the A, E and F rings of the natural product. Completion of the proposed research project will constitute the first total synthesis of nakadomarin A, and provide material for further biological investigations. In addition, the proposed synthetic analogs will provide information on structural features of nakadomarin A important for its biological activity.
| Ahrendt, Kateri A; Williams, Robert M (2004) A concise asymmetric synthesis of the ADE fragment of nakadomarin A. Org Lett 6:4539-41 |
