Exploring a new pattern of Eugenol derivatives to tackle Leishmaniasis

The essential oil rich in eugenol presents anticancer, antifungal and anti-inflammatory activity, in addition to the leishmanicidal effect. It was also discovered that some of its derivatives have higher leishmanicidal activity than eugenol itself. Thus, this work aims the synthesis of a novel pattern of Eugenol derivatives bearing a 1,2,3-triazole ring with optimal activity. Defining eugenol as the starting material, its nitration led to the formation of 4-allyl-2-methoxy-6-nitrophenol in 71% yield, which was then used to obtain 4-allyl-2-amino-6-methoxyphenol in 64% yield using metal Zinc as a reducing agent. The azidation of the diazonium salt derived from 4-allyl-2-amino-6-methoxyphenol furnished the desired key intermediate (4-allyl-2-azido-6-methoxyphenol) in 92% yield. Functionalized alkynes were successfully employed for the synthesis of 1,2,3-triazol eugenol derivatives under copper catalysis (1,3-dipolar cycloaddition). The synthesis of twelve derivatives were already accomplished (yield 40-99%). A library of such patterned molecules is under preparation and their potential leishmanicidal activities will be evaluated.