A rise in antibiotic resistant bacteria due to the overuse of antibiotics has led to a deficit in potent antibiotics. 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 work seeks to use intramolecular reductive amination, via Lewis acid catalysis and subsequent imine hydrogenation, as a viable method of azabicycle synthesis. Current work is focused on optimizing a synthetic route towards less strained 5,5 and 5,6 azabicyclic rings and then synthesizing analogs of the 5,3 ring present in ficellomycin. One route utilizes an alkylation reaction of N-benzyl and N-trifluoroacetoacetate pyrrolidine and piperidine methanols followed by the cyclization step. A second route transforms methyl acetoacetate into an aziridine, which can then be cyclized. Additional routes are also being explored to achieve the quick and inexpensive synthesis of azabicyclic compounds.

Synthesis of azabicycles using intramolecular reductive amination

251st National Meeting (2016)

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