(E)-1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-[4-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-en-1-one

Abstract

A novel prenylated chalcone, (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-[4-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-en-1-one was synthesized and the structure of the title compound was established by ¹H and ¹³C nuclear magnetic resonance (NMR), mass spectrometry (MS) and Fourier transform infrared (FT-IR) spectroscopy.

1. Introduction

Prenylated chalcones are associated with a variety of biological activities such as anti-malarial [1], antidiabetic [2], antifungal [3], antibacterial [4], antitumor [5], antioxidative [6] and anti-inflammatory [7] activities. Most of the above activities are influenced by the substitution of the flavonoid ring system with prenyl groups which increases the lipophilicity and confers the molecule a strong affinity to biological membranes [8]. These findings have prompted interest in the synthesis of naturally and non-naturally occurring prenylated flavonoids.

As part of our ongoing program on the studies of prenylated flavanoids [9], we report herein a facile synthetic approach in the synthesis of (E)-1-(2-hydroxy-4,6-dimethoxyphenyl)-3-[4-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-en-1-one (1). This prenylated chalcone is synthetically new and has not yet been isolated or reported elsewhere.

2. Synthesis

The starting material, 4-methoxy-3-(3-methylbut-2-enyl)benzaldehyde (2), was prepared according to the reported method [10]. Claisen-Schmidt condensation reaction of 4-methoxy-3-(3-methylbut-2-enyl)benzaldehyde (2) with compound (3) in aqueous/ethanolic solution by the action of potassium hydroxide-water-ethanolic [11] gave the desired chalcone in good yield (52.2%) with a melting point of 120–122 °C as a yellow crystalline solid. The structure of the compound was confirmed by IR, NMR (¹H and ¹³C) and MS.

3. Experimental

Melting points were recorded on a Leica Galen III Kofler micro melting point apparatus and are uncorrected. Infrared (IR) spectra were recorded on a Perkin-Elmer series 1600 spectrometer as thin film (NaCl windows) for liquid samples or KBr pellet for solid samples. Mass spectral data were recorded on a Thermo Scientific LTQ Orbitrap Discovery LCMS. The ¹H and ¹³C NMR spectra (300 and 75 MHz, respectively) were recorded on a Bruker Avance 300 spectrometer using CDCl₃ and acetone-d₆ as solvent. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.2 mm Merck pre-coated silica gel plates (60 F₂₅₄).

3.1. (E)-1-(2-Hydroxy-4,6-dimethoxyphenyl)-3-[4-methoxy-3-(3-methylbut-2-en-1-yl)phenyl]prop-2-en-1-one (1)

To a solution of 2-hydroxy-4,6-dimethoxyacetophenone (3) (100 mg, 0.39 mmol) and 4-methoxy-3-(3-methylbut-2-enyl)benzaldehyde (2) (100 mg, 0.43 mmol) in ethanol (10 mL) was added a 50% v/v aq. solution of KOH (0.8 mL). The mixture was then stirred at rt for 48 h. The mixture was poured into ice-water, acidified to pH ~5 with HCl (10%) (5 mL), and extracted with dichloromethane. The organic layer was washed with water and brine, dried over anhydrous MgSO₄, and evaporated under reduced pressure. The residual orange syrup was chromatographed on a silica gel column (PE:EtOAc, 9:1) to afford the title compound (1) (195 mg, 52.2%) as a yellow crystalline solid; R_f 0.52 (PE:EtOAc, 4:1).

m.p. 120–122 °C

IR ν_max (KBr) cm⁻¹: 1619 (C=O), 1581 & 1440 (C=C aromatic), 1158 (C-O)

¹H NMR (acetone-d₆) δ_H ppm: 1.76 (3H, s, H-4''), 1.77 (3H, s, H-5''), 3.35 (2H, d, J = 7.5 Hz, H-1''), 3.88 (3H, s, OCH₃), 3.92 (3H, s, OCH₃), 4.0 (3H, s, OCH₃), 5.36 (1H, m, H-2″), 6.10 (1H, d, J = 2.4 Hz, H-3'), 6.13 (1H, d, J = 2.4 Hz, H-5'), 7.04 (1H, d, J = 8.4 Hz, H-5), 7.55–7.58 (2H, m, with unresolved couplings due to overlapping, H-2 and H-6), 7.77 (1H, d, J = 15.6 Hz, H-α), 7.91 (1H, d, J = 15.6 Hz, H-β), 14.40 (1H, s, OH)

¹³C NMR (acetone-d₆) δ_C ppm: 17.33 (C-5'', CH₃), 25.46 (C-4'', CH₃), 28.5 (C-1'', CH₂), 55.51 (OCH₃), 55.57 (OCH₃), 55.97 (OCH₃), 90.51 (C-1', C-4°), 91.31 (C-5', C-H), 94.13 (C-3', C-H), 111.03 (C-5, C-H), 122.43 (C-2'', C-H), 125.07 (C-α, C-H), 128.12 (C-3, C-4°), 129.06 (C-6, C-H), 129.27 (C-2, C-H), 130.79 (C-1, C-4°), 132. 83 (C-3'', C-4°), 143.21 (C-β, C-H), 159.91 (C-2', C-4°), 163.14 (C-4, C-4°), 166. 80 (C-6', C-4°), 168.66 (C-4', C-4°), 192.78 (C=O, C-4°)

ESI-FTMS: m/z 383.25687 [M+H]⁺, C₂₃H₂₇O₅ requires 383.18585