Design, synthesis and biological evaluations of quinolone amides against African trypanosomiasis with improved solubility.

The human African trypanosomiasis is a devastating parasitic infection, which is caused by the protozoan Trypanosoma brucei and transmitted by the bite of the tsetse fly. An untreated infection usually results in death and only few drugs with significant drawbacks are currently available for treatment. Previous investigations revealed the quinolone amide MB007 as a lead compound with an excellent selectivity for T.

Apical Functionalization of Tribenzotriquinacenes.

The introduction of one alkyne moiety at the central carbon atom of the tripodal tribenzotriquinacene scaffold allows easy access to a great variety of apically functionalized derivatives. The spatially well-separated arrangement of different functional units on the convex face and outer rim was further proven by single-crystal X-ray studies. Subsequent modifications that feature a general protecting group-free strategy for the demethylation of protected catechols in the presence of a terminal alkyne group, an azide-alkyne Huisgen cycloaddition, and Sonogashira cross-coupling reactions showcase the high synthetic potential of this modular approach for tribenzotriquinacene derivatization.