Synthetic Approaches towards Azabicyclic Compounds

The overuse of antibiotics has contributed to a recent increase in drug-resistant strains of bacteria. Thus, research into new compounds that exhibit novel modes of action will aid in the development of antibiotics that are active against drug-resistant strains. Based on the promising activity of ficellomycin, which contains a unique and highly strained azabicyclo[3.1.0]hexane ring system, this project seeks to improve upon existing methodologies for the synthesis of the azabicycle moiety.  This work explores intramolecular reductive amination, via Lewis acid catalysis and subsequent imine hydrogenation, as a viable method of azabicycle synthesis. One possible route utilizes an alkylation reaction of protected pyrrolidine and piperidine methanols followed by the cyclization step. Another route begins with methyl acetoacetate and uses an alkylation followed by epoxidation and aziridination to form the molecule needed for cyclization.