Presenter: Muhammad Khalifa
Mentor: Michael Haley
Oral Presentation
Major: Biochemistry
Aryl amidines have been used against a variety of diseases, most notably pneumocystis pneumonia. They continue to be relevant in the search for cures against malaria, Alzheimer’s disease, and myotonic dystrophy type
1 (DM1). Current methods of amidine synthesis feature harsh, acidic reaction conditions that limit possibilities for functionalization of the amidine group, a process of particular interest in developing small molecule therapeutics
for DM1. Preparation of amidines via basic conditions has been described, but not well studied. Here we outline a method of preparing N-substituted aryl amidines under alkaline conditions and examine the accessibility of series
of amidines to delineate important properties of this synthetic approach. Our results indicate that increasing the nucleophilicity of the amine and/or increasing the electrophilicity of the nitrile afford higher yields of the desired amidine. Results also show that alkaline synthesis is sufficiently chemoselective to form amidines in the presence of competing, nucleophilic aromatic substitution sites on the nitrile. Featuring reaction times at least 50% shorter, up to 40% greater yields, and better compatibility with a broad range of starting materials, our method of alkaline amidine synthesis makes accessible a host of new N-substituted amidines for study in a variety of diseases previously described.