Biosynthesis of Resveratrol Dimers by Regioselective Oxidative Coupling Reaction

Abstract

A wide array of natural resveratrol dimers was prepared by the regioselective oxidative coupling reaction of 3,5-di-(tert-­butyl)resveratrol using several types of metal oxidants (Ag₂O, Ag₂CO₃, MnO₂, and FeCl₃˙6H₂O) in different solvent systems (benzene-acetone and dichloromethane). Subsequent debutylation of these coupling products resulted in racemic pallidol and ampelosin F.

Key words

resveratrol dimmer - pallidol - ampelosin F - oxidative coupling - biosynthesis

References and Notes

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9

The spectra data of compound 8 were completely consistent with literature data.⁸

10

Analytical Data for Compound 9
Pale yellow amorphous powder. IR (neat): 3641, 3348, 2957, 1688, 1605, 1510, 1432, 1238, 1018 cm^-¹. ^¹H NMR (400 MHz, acetone-d ₆): δ = 1.40 (s, 36 H, t-Bu), 3.91 (br s, 2 H, H-8, H-8′), 4.58 (br s, 2 H, H-7, H-7′), 5.84 (br s, 2H, OH), 6.18 (d, J = 2.0 Hz, 2 H, H-14, H-14′), 6.62 (d, J = 1.2 Hz, 2 H, H-12, H-12′), 7.06 (br s, 4 H, H-3, H-5, H-3′, H-5′), 7.88 (br s, 2 H, OH), 8.09 (br s, 2 H, OH). ^¹³C NMR (100 MHz, acetone-d ₆): δ = 30.8, 35.0, 54.5, 60.5, 102.3, 103.3, 123.4, 124.4, 137.6, 137.8, 150.2, 152.7, 155.3, 159.1. ESI-HRMS: m/z calcd for C₄₄H₅₄O₆ + H: 679.3993; found: 679.3999.

11

Analytical Data for Compound 10
Pale yellow amorphous powder. IR (neat): 3420, 2852, 1628, 1530, 1472, 1308, 1054 cm^-¹. ^¹H NMR (400 MHz, acetone-d ₆): δ = 1.25 (s, 18 H, t-Bu), 1.40 (s, 18 H, t-Bu), 3.28 (br s, 1 H, H-8), 3.67 (br s, 1 H, H-7′), 4.14 (br s, 1 H, H-8′), 4.22 (br s, 1 H, H-7), 5.73 (br s, 1 H, OH), 5.83 (br s, 1 H, OH), 6.08 (d, J = 1.6 Hz, 1 H, H-14), 6.15 (d, J = 2.0 Hz, 1 H, H-14′), 6.44 (d, J = 2.0 Hz, 1 H, H-12′), 6.50 (d, J = 1.6 Hz, 1 H, H-12), 6.71 (br s, 2 H, H-2′, H-6′), 7.12 (br s, 2 H, H-2, H-6), 7.35 (br s, 1 H, OH), 7.92 (br s, 1 H, OH), 7.93 (br s, 1 H, OH), 8.01 (br s, 1 H, OH). ^¹³C NMR (100 MHz, acetone-d ₆): δ = 30.6, 30.8, 35.0, 35.1, 48.0, 49.3, 51.9, 59.6, 101.6, 104.3, 105.7, 114.2, 124.8, 125.3, 128.2, 135.8, 137.4, 137.6, 138.2, 147.4, 147.8, 152.7, 153.0, 157.1, 157.9, 158.5. ESI-HRMS: m/z calcd for C₄₄H₅₄O₆ + H: 679.3993; found: 679.3988.

14

Representative Procedure
A solution of AlCl₃ (0.1 g, 0.72 mmol) in MeNO₂ (1 mL) was added to a solution of compound 9 (46 mg, 0.06 mmol) in dry toluene (10 mL) at 60 ˚C. The reaction mixture was stirred for 30 min. Then quenched with ice-water (5 mL), and extracted with EtOAc. The combined organic layer was washed with sat. brine and then dried over MgSO₄. The solvent was removed under reduced pressure and the residue puried on a silica gel (CH₂Cl₂-MeOH, 15:1) to afford (±)-pallidol (5, 24 mg, 85%) as a pale yellow amorphous powder. IR (neat): 3402, 2956, 2826, 1638, 1508, 1462, 1246, 1080 cm^-¹. ^¹H NMR (400 MHz, acetone-d ₆): δ = 3.80 (br s, 2 H, H-8, H-8′), 4.56 (br s, 2 H, H-7, H-7′), 6.18 (d, J = 2.0 Hz, 2 H, H-14, H-14′), 6.61 (d, J = 2.0 Hz, 2 H, H-12, H-12′), 6.70 (d, J = 8.4 Hz, 4 H, H-3, H-3′, H-5, H-5′), 6.97 (d, J = 8.4 Hz, 4 H, H-2, H-2′, H-6, H-6′), 7.84 (br s, 2 H, OH), 8.06 (br s, 2 H, OH), 8.08 (br s, 2 H, OH). ^¹³C NMR (100 MHz, acetone-d ₆): δ = 54.0, 60.5, 102.5, 103.4, 115.8, 123.2, 129.0, 137.7, 150.3, 155.3, 156.3, 159.4. ESI-HRMS: m/z calcd for C₂₈H₂₂O₆ + H: 455.1489; found: 455.1490.

15

Analytical Data for ()-Ampelosin F (6)
Pale yellow amorphous powder. IR (neat): 3380, 2854, 1628, 1495, 1354, 1205, 1055 cm^-¹. ^¹H NMR (400 MHz, acetone-d ₆): δ = 3.35 (br s, 1 H, H-8), 3.64 (br s, 1 H, H-7′), 4.12 (br s, 1 H, H-8′), 4.19 (br s, 1 H, H-7), 6.06 (d, J = 2.0 Hz, 1 H, H-14), 6.15 (d, J = 2.0 Hz, 1 H, H-14′), 6.44 (d, J = 2.0 Hz, 1 H, H-12′), 6.52 (d, J = 2.0 Hz, 1 H, H-12), 6.56 (d, J = 8.0 Hz, 2 H, H-3′, H-5′), 6.75 (d, J = 8.0 Hz, 2 H, H-3, H-5), 6.78 (d, J = 8.0 Hz, 2 H, H-2′, H-6′), 7.08 (d, J = 8.0 Hz, 2 H, H-2, H-6), 7.48 (br s, 1 H, OH), 7.88 (br s, 1 H, OH), 7.97 (br s, 1 H, OH), 8.03 (br s, 1 H, OH), 8.04 (br s, 1 H, OH), 8.10 (br s, 1 H, OH). ^¹³C NMR (100 MHz, acetone-d ₆): δ = 46.9, 49.4, 50.2, 58.0, 101.6, 101.9, 104.0, 105.4, 113.0, 113.1, 115.3, 127.5, 129.0, 129.6, 135.2, 138.1, 147.0, 147.3, 152.9, 156.0, 156.9, 157.5, 158.0, 158.4. ESI-HRMS: m/z calcd for C₂₈H₂₂O₆ + H: 455.1489; found: 455.1496.