Abstract
Chagas disease and visceral leishmaniasis are neglected protozoan diseases with significant impact in developing countries. Due to the limited number and toxicity of current therapies, new drug leads are urgently needed. In this work, four aporphine natural products were synthesized using an enantioselective, modular and convergent strategy, comprising eight steps in the longest linear sequence; key steps included Bischler-Napieralski cyclization/Noyori asymmetric reduction to construct the tetrahydroisoquinolines, and palladium-catalyzed arylation to close the C ring. Norglaucine, nordicentrine and dicentrine showed promising bioactivity against T. cruzi and L. infantum, suggesting potential for further development of these scaffolds as antiparasitic agents.
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