Regioselective Biomimetic Synthesis of Dimeric Oxyresveratrol Derivatives

Abstract

Oxyresveratrol and its methylated derivative as coupling precursors were efficiently prepared in four steps, with Wittig reactions and subsequent isomerization reactions as the key steps. The coupling reactions of oxyresveratrol under various oxidative conditions gave a complex and inseparable mixture of coupling products. The oxidative dimerizations of methylated oxyresveratrols catalyzed by horseradish peroxidase–H₂O₂ or FeCl₃·6H₂O in an acetone system predominantly produced the 8–5-coupled and 8–10-coupled dihydrobenzofuran-type dimers, respectively. This regioselective biomimetic strategy might be useful in synthesizing other dimeric oxyresveratrol derivatives.

Key words

oxyresveratrol - biomimetic synthesis - oligostilbenes - oxidative coupling - dimerization - regioselectivity

Publication History

Received: 08 July 2020

Accepted: 03 August 2020

Article published online:
01 September 2020

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• 14 5-[(E)-2-(4-Hydroxy-2-methoxyphenyl)ethenyl]benzene-1,3-diol [(E)-15] Pale-yellow oil; yield: 1.77 g (91%). ¹H NMR (500 MHz, acetone-d ₆): δ = 3.85 (s, 3 H), 6.24 (t, J = 2.0 Hz, 1 H), 6.46 (dd, J = 8.5, 2.0 Hz, 1 H), 6.49 (d, J = 2.0 Hz, 1 H), 6.52 (d, J = 2.0 Hz, 2 H), 6.88 (d, J = 16.5 Hz, 1 H), 7.30 (d, J = 16.5 Hz, 1 H), 7.45 (d, J = 8.5 Hz, 1 H), 8.16 (br s, 2 H), 8.51 (br s, 1 H). ¹³C NMR (125 MHz, acetone-d ₆): δ = 55.8, 99.8, 99.9, 102.4, 105.5 (2 C), 108.5, 118.7, 123.9, 126.8, 127.9, 141.5, 159.2, 159.5, 159.6. HRMS (ESI): m/z [M –H]⁺ calcd for C₁₅H₁₃O₄: 257.08193; found: 257.08191.
• 15 5-{(E)-2-[3-(3,5-Dihydroxyphenyl)-2-(4-hydroxy-2-methoxyphenyl)-6-methoxy-2,3-dihydro-1-benzofuran-5-yl]ethenyl}benzene-1,3-diol (16) Yellowish amorphous powder; yield: 31 mg (62%). ¹H NMR (500 MHz, acetone-d ₆): δ = 3.77 (s, 3 H), 3.94 (s, 3 H), 4.36 (d, J = 5.0 Hz, 1 H), 5.73 (d, J = 5.0 Hz, 1 H), 6.21 (d, J = 2.0 Hz, 2 H), 6.23 (t, J = 2.0 Hz, 1 H), 6.24 (t, J = 2.0 Hz, 1 H), 6.40 (dd, J = 8.5, 2.0 Hz, 1 H), 6.50 (d, J = 2.0 Hz, 2 H), 6.52 (d, J = 2.0 Hz, 1 H), 6.64 (d, J = 2.0 Hz, 1 H), 6.84 (d, J = 16.5 Hz, 1 H), 7.12 (d, J = 8.5 Hz, 1 H), 7.32 (d, J = 2.0 Hz, 1 H), 7.35 (d, J = 16.5 Hz, 1 H), 8.15 (br s, 2 H), 8.16 (br s, 2 H), 8.46 (br s, 1 H). ¹³C NMR (125 MHz, acetone-d ₆): δ = 55.7, 56.2, 89.8, 94.3, 100.0, 102.0, 102.5, 105.5, 105.6 (2 C), 107.0, 107.1 (2 C), 107.6, 119.8, 121.2, 122.9 (2 C), 123.4, 123.9, 126.8, 128.1, 141.4, 147.2, 159.0, 159.1, 159.5, 159.6 (2 C), 162.2. HRMS (ESI): m/z [M – H]⁺ calcd for C₃₀H₂₅O₈: 513.15549; found: 513.15547.
• 16 5-{6-Hydroxy-2-(4-hydroxy-2-methoxyphenyl)-5-[(E)-2-(3-hydroxy-5-methoxyphenyl)ethenyl]-2,3-dihydro-1-benzofuran-3-yl}benzene-1,3-diol (18) Yellowish amorphous powder; yield: 15 mg (45%). ¹H NMR (500 MHz, acetone-d ₆): δ = 3.76 (s, 3 H), 3.83 (s, 3 H), 4.36 (d, J = 5.0 Hz, 1 H), 5.67 (d, J = 5.0 Hz, 1 H), 6.20 (dd, J = 8.5, 2.0 Hz, 1 H), 6.26 (d, J = 2.0 Hz, 2 H), 6.34 (dd, J = 8.0, 2.0 Hz, 1 H), 6.36 (d, J = 2.0 Hz, 2 H), 6.41 (d, J = 2.0 Hz, 1 H), 6.51 (d, J = 2.0 Hz, 1 H), 6.68 (d, J = 2.0 Hz, 1 H), 6.76 (d, J = 16.5 Hz, 1 H), 7.05 (d, J = 8.0 Hz, 1 H), 7.15 (d, J = 16.5 Hz, 1 H), 7.16 (d, J = 8.0 Hz, 1 H). ¹³C NMR (125 MHz, acetone-d ₆): δ = 55.6, 55.7, 55.8, 89.1, 99.7, 99.8, 103.9, 107.0, 107.3, 108.3, 118.6, 120.1, 122.3, 123.8, 125.3, 125.6, 127.2, 127.8, 128.1, 128.4, 137.2, 148.1, 151.9, 158.5 (2 C), 159.3 (2 C), 159.5, 162.8 (2 C). HRMS (ESI): m/z [M – H]⁺ calcd for C₃₀H₂₅O₈: 513.15549; found: 513.15546.