Human African trypanosomiasis, also known as African sleeping sickness, is a neglected tropical disease with inadequate therapeutic options. We have launched a collaborative new lead discovery venture using our repository of extracts and natural product compounds as input into our growth inhibition primary screen against Trypanosoma brucei. Careful evaluation of the spectral data of the natural products and derivatives allowed for the elucidation of the absolute configuration (using the modified Mosher's method) of two new peroxiterpenes: (+)-muqubilone B (1a) and (-)-ent-muqubilone (3a). Five known compounds were also isolated: (+)-sigmosceptrellin A (4a), (+)-sigmosceptrellin A methyl ester (4b), (-)-sigmosceptrellin B (5), (+)-epi-muqubillin A (6), and (-)-epi-nuapapuin B methyl ester (7). The isolated peroxiterpenes demonstrated activities in the range IC(50) = 0.2-2 mug/mL.