SYNTHESIS OF BIOTINYLATED AND C4/N1 SUBSTITUTED β-LACTAMS
Degree awarded: M.S. Chemistry. American University
The spread of antibiotic resistance inexorably diminishes effective treatments available against bacterial infections. β-lactam antibiotics inhibit bacterial cell wall synthesis, pathways unique to bacteria, and thus are generally safe and effective. Monocyclic β-lactam antibiotics with aryl-thio moieties at C4 were shown to be effective against Moraxella catharralis (M. cat) and Mycobacterium tuberculosis (Mtb), bacteria traditionally resistant to β-lactams. A set of monocylic β-lactams with trifluoromethyl-substituted thiophenol moieties were synthesized and then carbamoylated. Their activity against M.cat. and Mtb. is reported. The mechanism and cellular target of these β-lactams is currently unknown. To that end, we have developed a novel synthesis to tag a derivative of these monocyclic β-lactams with Biotin (Vitamin H). The design, synthesis and evaluation of antimicrobial activity are described.