Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors

This work was funded by the Leverhulme Trust (GJF), and the Wellcome Trust (TKS, WT 093228).Neglected tropical diseases caused by parasitic infections are an on-going and increasing concern and burden to human and animal health, having the most devastating effect on the world’s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5 isoxazoles, furoxans and furazans. Several of these compounds maintain low micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.PostprintPeer reviewe

Radical oxidation of 17-functionalized 14alpha-hydroxy steroids

The radical oxidation of 14a-hydroxy steroids with various functional groups at C-17 was studied. Lead tetraacetate and ceric ammonium nitrate were used as oxidizing agents. It was shown that reactions of this type afforded complex mixtures of compounds. However, the radical oxidation of 14a-hydroxy-17-oxo steroid (lead tetraacetate version of the hypoiodite reaction) proceeded smoothly with formation of the 13,14-secosteroid in up to 85"ield. The structure and conformation of the formed 13a-iodo-3a,5-cyclo-13,14-seco-5a-androst-5-ene-14,17-dione was determined by X-ray analysi