Synthesis and antileishmanial activity of natural dehydrodieugenol and its mono- and dimethyl ethers

Abstract

The study of chemistry of naturally occurring compounds and the synthesis of their derivatives is fundamentally important for the development of new drugs. In this work, dehydrodieugenol (DHDE) was obtained through oxidative coupling of eugenol, promoted by an aqueous mixture of potassium ferricyanide (K3[Fe(CN)6]) and NH3 · H2O. The partial methoxylation of DHDE with MeI and K2CO3 mainly resulted in the molecular‐shaped monomethyl ether (DHDE‐1MeO) and its dimethyl ether derivative (DHDE‐2MeO). The products from the reactions were characterized by 1H‐ and 13C‐NMR spectroscopy. Additionally, these studies have reported the antileishmanial activity of DHDE against Leishmania amazonensis (IC50 value of 42.20 μg ml−1) and shown that partial methoxylation of DHDE results in a significant increase in its antiparasitic activity (IC50 value of 13.68 μg ml−1). Based on in vitro bioassays, DHDE‐1MeO has shown the highest leishmanicidal activity in promastigota form. Production by direct one‐step synthesis of this monomethoxylated compound can be considered to be a cost‐effective and environmentally friendly method with a short reaction time.