Thursday, August 25, 2016 - 11:00am Chemistry Building, Room 400 Organic Seminar Total Synthesis of Pyrrole Imidazole Alkaloids enabled by a Unique Chemoselective Oxidation The Axinellamines, Massadines, and Palau’amine are complex marine natural products belonging to the oroidin family isolated from sponge agelas oroides. Their complex structures, varying modes of functionalities, and biological activities have made them attractive targets for total synthesis. Although isolated in 1993, Palau’amine was not synthesized until seven years later due to the incorrect structure being reported. Revision of the structure, as well as the development of a unique chemoselective oxidation enabled the total synthesis of this natural product as well as the Axinellamines and Massadines. The approach taken by many groups towards the total syntheses of these natural products was to build a common core. The direct oxidation created by Baran and coworkers bridged the gap between building a core and total synthesis. Baran’s chemoselective oxidation provided a direct route from the guanidine moiety to the hemiaminal functionality present in these complex structures. Before the syntheses of these pyrrole imidazole alkaloids, the chemistry of building a core was approached in ways that would already have a pre-oxidized carbon installed to access the hemiaminal without the use of a direct oxidation step. Baran’s unique chemoselective oxidation took a direct approach and is the first for this kind of chemistry. The unique selectivity this oxidation delivered is highlighted by the installation of the hydroxyl despite the many functionalities present in these complex structures. 1. Baran, P. S., et al. Angew. Chem. Int. Ed. 2007, 46, 6586-6594. 2. Baran, P. S., et al. Angew. Chem. Int. Ed. 2010, 49, 1095-1098. 3. Ferreira-Pereira, A., et al. J. Nat. Prod. 2011, 74, 279–282 4. Rasapalli, S., et al. Org. Biomol. Chem. 2013, 11, 4133-4137 5. Chen, C., et al. Chem. Commun. 2014, 50, 8628-8639 6. Quinn, R. J., et al. J. Org. Chem. 1999, 64, 731-735. 7. Baran, P. S., et al. Angew. Chem. Int. Ed. 2008, 47, 3578-3580. 8. Carreira, E. M., et al. J. Am. Chem. Soc. 2000, 122, 8793-8794. 9. Lovely, C. J., et al. Org. Lett. 2007, 9, 3861-3864. 10. Baran, P. S., et al. Angew. Chem. Int. Ed. 2008, 47, 3581-3583. 11. Hampson, N. A.; Lee, J. B. J. Chem. Soc. C, 1970, 815-817 12. Lee, J. B. et al. Tetrahedron. 1972, 29, 751-752. 13. Fusetani, N., et al. Org. Lett. 2003, 5, 2255-2257. 14. Kock, M.; Baran, P. S. Angew. Chem. Int. Ed. 2007, 46, 6721-6724. 15. Baran, P. S., et al. Angew. Chem. Int. Ed. 2008, 49, 16490-16491. 16. Scheuer, P. J., et al. J. Am. Chem. Soc. 1993, 115, 3376-3377. 17. Scheuer, P. J., et al. J. Org. Chem. 1998, 63, 3281-3286. 18. Kock, M., et al. Angew. Chem. Int. Ed. 2007, 46, 2320 –2324. 19. Romo, D., et al. Org. Lett. 2001, 3, 1535-1538. 20. Overman, L. E., et al. Tetrahedron. 2004, 60, 9559-9568. 21. Baran, P. S., et al. Chem. Soc. Rev., 2011, 40, 1976–1991 22. Namba, K., et al. Nature Commun. 2015, 6, 1-9.