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 · H2 O. The partial methoxylation of DHDE with MeI and K2 CO3 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 (1) H- and (13) C-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.

Neolignans isolated from twigs of Nectandra leucantha Ness & Mart (Lauraceae) displayed in vitro antileishmanial activity

“…The pattern related to a tetrasubstituted aromatic ring confirmed the C-C linkage between two aromatic rings. The spectroscopic data of 1 – 6 were in accordance with those previously reported in the literature [ 6 , 7 , 12 – 18 ], allowing the identification of dehydrodieugenol B ( 1 ), 1-(8-propenyl)-3-[3′-methoxy-1′-(8-propenyl)phenoxy]-4,5-dimethoxybenzene ( 2 ), 1-[(7R)-hydroxy-8-propenyl]-3-[3′-methoxy-1′-(8′-propenyl)-phenoxy]-4-hydroxy-5-methoxybenzene ( 3 ), 1-[(7R)-hydroxy-8-propenyl]-3-[3′-methoxy-1′-(8′-propenyl)-phenoxy]-4,5-dimethoxybenzene ( 4 ), dihydrodieugenol ( 5 ), and dehydrodieugenol dimethyl ether ( 6 ) as shown in Fig. 2 .…”

“…Compound 6 conforms with many of these criteria and could be eventually be addressed to the hit-to-lead optimization phase. Although the activity of compound 6 against promastigote forms of L. (L.) amazonensis has previously been reported in the literature [ 18 ], the present work described the activity of compound 6 against intracellular amastigotes of L. (L.) infantum , the clinically relevant form of Leishmania , which results in a fatal visceral disease if untreated [ 22 ].…”

Biseugenol Exhibited Anti-Inflammatory and Anti-Asthmatic Effects in an Asthma Mouse Model of Mixed-Granulocytic Asthma

“…1 H and 13 C NMR (nuclear magnetic resonance) as well as HRESIMS (high resolution electrospray ionization mass spectrometry) spectra (see Supplementary Materials ) of natural product were compared with those reported in the literature [ 9 ], allowing for the identification of biseugenol ( Figure 1 ). Based on the reduced amounts of natural biseugenol, insufficient to perform the biological assays, the preparation of this compound was performed using oxidative coupling of eugenol (70% yield).…”

“…The preparation of biseugenol involved the dimerization of commercial eugenol through an oxidative coupling reaction, according to the procedure previously reported in the literature [ 9 ]. Briefly, from 1.64 g of K 3 [Fe(CN) 6 ] and 820 mg of eugenol, 560 mg of biseugenol was obtained (70% yield) after recrystallization using absolute EtOH.…”

Use of Natural Products in Leishmaniasis Chemotherapy: An Overview

“…The efficacy of a lignin found in garlic (Allium sativum) against L. amazonensis promastigotes was investigated. Dehydrodieuginol (DHDE), an ortho-biphenyl neolignan, showed an IC 50 value of 42.2 µg/mL (Rodrigues et al, 2016). The efficacy of 2,3-dihydrobenzofuran, a neolignan used to treat liver diseases and vascular diseases of the brain and found in propolis and other plants, against L. amazonensis was studied.…”