The original goal of this grant was the development of new methodology in the area of synthetic organic chemistry, based upon novel photochemistry of 4-pyrones. This chemistry allows for the rapid construction of complex, polycyclic structures, corresponding in many cases to biomedically important natural products, from simple, readily available precursors. In the renewal, a variety of new directions are presented, along with further exploration of the issues covered during the current grant period. An important focus in this application is the development of stereoselective versions of the reactions at hand. As many as five new chiral centers are created from achiral precursors. Thus, methods for forming these centers with good control of absolute stereochemistry are critical to fully exploit this chemistry. In particular, the use of Lewis acids to control the torquoselectivity of the Nazarov electrocyclization reaction will be examined. Methodology already developed or under current development will be applied to the synthesis of two challenging natural product targets. The intramolecular crossed [4+4]-photocycloaddition chemistry of 2-pyrones will be used in a synthesis of 7,8-epoxy-4-basmen-6-one. Cyclization/fragmentation approaches, using either 4-pyrone photochemistry or the Nazarov reaction, will be applied to taxinine. Long term goals include the eventual application of this methodology to taxol and related analogues.
| Rostami, Ali; Wang, Yong; Arif, Atta M et al. (2007) Intramolecular azide trapping of the Nazarov intermediate: formation of peroxy-bridged indolizidinones via a deep-seated rearrangement and aerobic oxidation. Org Lett 9:703-6 |
| Mazzola Jr, Robert D; White, Timothy D; Vollmer-Snarr, Heidi R et al. (2005) Stereoselective Nazarov cyclizations of bridged bicyclic dienones. Org Lett 7:2799-801 |
