Abstract:

Human Babesiosis is a parasitic disease of the red blood cells caused primarily by the parasite Babesia duncani. Part one of this talk will discuss our work toward developing labeled analogs of the anti-hypertensive compound Fosinopril, which was found to possess potent anti-babesial activity. A range of C–H azidation techniques were attempted, but success was found in amidation of Fosinopril with a novel biotin derivative. Bromination of Fosinopril proved successful, though subsequent cross-couplings failed with functionalized biotin derivatives

Part two will discuss our synthesis of novel pyrroloiminiquinone (PIQ) alkaloids with potent anti-parasitic activity against both P. falciparum and B. duncani. A readily prepared common intermediate was elaborated to a variety of unnatural PIQ alkaloids, some with sub-nanomolar activity against B. duncani. Progress toward a novel synthetic sequence employing a Fischer indolization to produce a key indole scaffold will also be discussed. Currently we are investigating mild conditions to perform the desired Fischer indolization on an azide-containing substrate.