Erinacines A through 1, cyathane diterpenes, are of significant medicinal interest because they are potent stimulators of nerve growth (NGF) synthesis. NGF is a potential treatment for degenerative neural disorders such as Alzheimer's disease and for promoting peripheral nerve regeneration. However, NGF's inability to cross the blood-brain barriers limits its utility. Potential drugs that stimulate NGF synthesis by brain cell show great promise as new medicines. Considering the therapeutic potential of the Erinacines combined with their limited ability, a general and concise route to these molecules and potential derivatives would be of great interest. This proposal outlines a synthesis of complex 7-membered rings by focusing on the first application of the Rh (I) catalyzed [5+2] intramolecular cycloaddition between an alkene and a vinylcylcopropane. Additionally, the application of this methodology to the total synthesis of Erinacine E is proposed. The synthesis should be valuable for finding new therapeutic leads while simultaneously developing an approach to an important and emerging class of natural products.
