A bi-directional centrosymmetric strategy towards the synthesis of marine polyether natural products Sophie Woolford, Dr Chih-Chung Tseng , and Prof. J. Stephen Clark University of Glasgow, UK Over the years numerous marine polycyclic ether natural products have been isolated from algal bloom causing dinoflagellate species, and have since become particularly interesting targets for total synthesis due to their complex structures and diverse biological activities. 1 Many of these natural products are associated with human sea food poisoning and are potent neurotoxins to mammals due to their high affinities to voltage-sensitive ion- channel proteins. 2 A large number also show potent antifungal and cytotoxic activities, however the full scope of their biological activities remain unknown and therefore development of efficient strategies towards their synthesis is invaluable. 3,4
This project utilizes the apparent and latent symmetry embedded within these natural products to construct fragments through a bi-directional centrosymmetric approach, which allows for rapid and efficient elaboration of the ring systems. These achiral centrosymmetric systems can be rapidly built up, and then desymmetrisation and selective functionalisation can be carried out utilising methods such as methyl group insertion or ring expansion chemistry to give a variety of natural product fragments.
Three key methodologies have now been developed: in-situ epoxidation and allylation to access the diketone functionality; Michael addition/RCM to build up sequential rings; and desymmetrisation to differentiate between the sides of the molecule with excellent enantioselectivity.
With all key methodology established, work is currently ongoing utilising this for the elaboration of common intermediates into several marine polyether natural product fragments. References 1. C. Nicolaou, M. O. Frederick, R. J. Aversa, Angew. Chem. Int. Ed. 2008 , 47 , 7182 2. Yasumoto, M. Murata, Chem. Rev. 1993 , 93 , 1897 3. Nagai, M. Murata, K. Torigoe, M. Statke, T. Yasumoto, J. Org. Chem. 1992 , 57 , 5448 4. Satake, M. Shoji, Y. Oshima, H. Naoki, T. Fujita, T. Yasumoto, Tetrahedron Lett. 2002 , 43 , 5829
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