Synthesis of uniflorol B, a chromanone metabolite of Calea uniflora, and investigation of novel analogues as anti-leishmanial agents

Abstract

In this work, we report the first synthesis of the anti-leishmanial natural product uniflorol B. Uniflorol B is a chromanone metabolite first isolated from the Brazilian medicinal plant Calea uniflora Less., and possesses anti-leishmanial activity. We prepared uniflorol B, the E isomer of the natural product, through an 8-step approach featuring Kabbe condensation, regioselective ketone reduction and Morita-Baylis-Hillman elaboration of the side chain. We extended the methodology to four novel analogues and tested all compounds for their activity against various species of Leishmania. The most potent activity was seen with compound 18, with an IC50 of 64.8 µM against L. braziliensis.