PART I: CHLORONIUM-INDUCED SEMIPINACOL REARRANGEMENT FOR THE CONSTRUCTION OF THE TETRACYCLIC CORE OF ACUTUMINE AND PROGRESS TOWARD A TOTAL SYNTHESIS OF ACUTUMINE PART II: PROGRESS TOWARD A TOTAL SYNTHESIS OF PAECILOMYCINE A

Abstract

Acutumine is a highly functionalized tetracyclic natural product, containing a [4.3.3]-propellane core and a 5,5-spirocycle. We were inspired to develop a novel method to synthesize this natural product which possesses anti-amnesia and memory enhancing activity. We demonstrated that a chloronium-induced semipinacol rearrangement is a viable way to install the spirocycle in a model system containing much of the complexity of the natural product. We then pursued ways to incorporate all of the necessary functionality while still being able to make use of the key step we developed. We found a facile method to form a [3.3.0]-bicyclic core through an enyne hydrative cyclization, reducing the length of our synthesis significantly. Unfortunately, we were never able to elaborate this intermediate to the natural product.

We were also interested in a synthesis of the natural product paecilomycine A, which has potential to be a therapeutic agent in the treatment of neurodegenerative diseases. Paecilomycine A has a tetracyclic core with five stereogenic centers, four of which are contiguous, and two are adjacent quaternary centers. We proposed forming the adjacent quaternary stereogenic centers in a radical reaction, beginning from a radical epoxide opening which would lead to radical addition into a cyclopentenone moiety. We developed a convergent synthesis and synthesized the two fragments of the natural product, but have been unable to join these two fragments to test the key step.