*2.1. Chemistry*

#### 2.1.1. General Information

Unless noted otherwise, all reactions were performed in dry solvents under anhydrous conditions and argon atmosphere. The reaction flasks were flame-dried before use, and all solvents for extraction and chromatography were reagen<sup>t</sup> grade. All reagents were purchased from commercial suppliers and were used without further purification. TLC (thin-layer chromatography) was conducted for monitoring reaction progress with 0.25 mm silica gel plates (Merck, Kenilworth, NJ, USA). Silica gel 60 (230–400 mesh, Merck, Kenilworth, NJ, USA) was used for flash column chromatography with the indicated solvents. 1H and 13C spectra were recorded on a Brucker Analytik ADVANCE digital 500 (500 MHz) (Billerica, MA, USA) or BRUKER AVANCE-800 (800 MHz) (Billerica, MA, USA). 1H-NMR data are reported as follows: chemical shift, multiplicity (singlet, s; doublet, d; triplet, t; quartet, q; broad b; and/or multiple resonances), coupling constant in hertz (Hz), and number of protons. Chemical shifts are stated in ppm (parts per million, δ) downfield from tetramethylsilane (TMS) and are referenced to the deuterated solvent (CDCl3 and DMSO-d6). IR (infrared) spectra were recorded on a FT-IR-4200 (JASCO, Tokyo, Japan) spectrometer. Low- and high-resolution mass spectra were acquired with JMS-700 (JEOL, Tokyo, Japan) equipment.

## 2.1.2. Experimental Section

*(E)-3-(2-(Benzyloxy)phenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)prop-2-en-1-one* (6). To a solution of 4,6-dimethoxy-2-hydroxybenzophenone 4 (700 mg, 3.57 mmol) and 2-(benzyloxy)benzaldehyde 5 (1100 mg, 5.35 mmol) in ethyl alcohol (11 mL), KOH (400 mg, 7.14 mmol) was added at room temperature. After stirring at the same temperature for 48 h, the reaction mixture was concentrated in vacuo. The reaction mixture was quenched with 1*N* aqueous solution of hydrochloric acid and extracted with EtOAc (ethyl acetate). The combined organic layer was washed with saturated sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Purification of the concentrated residue by flash column chromatography (EtOAc/*n*-Hexane = 1 : 40 to 1 : 10) afforded 1500 mg (75%) of chalcone 6 as a yellow powder. m.p.: 114–115 ◦C; Rf = 0.25 (EtOAc : *n*-Hexane = 1 : 10); 1H NMR (800 MHz, CDCl3) δ 14.37 (s, 1H), 8.17 (d, 1H, *J* = 15.8 Hz), 8.02 (d, 1H, *J* = 15.7 Hz), 7.62 (dd, 1H, *J* = 1.5, 7.7 Hz), 7.46 (d, 2H, *J* =7.6 Hz), 7.39-7.37 (m, 2H), 7.33-7.30 (m, 2H), 7.00 (t, 1H, *J* = 7.5 Hz), 6.87 (d, 1H, *J* = 8.2 Hz), 6.10 (d, 1H, *J* = 2.3 Hz), 5.91 (d, 1H, *J* = 2.3 Hz), 5.20 (s, 2H), 3.83 (s, 3H), 3.72 (s, 3H); 13C NMR (200 MHz, CDCl3) δ 193.3, 168.4, 166.2, 162.6, 157.9, 138.1, 136.9, 131.4, 129.5, 128.8, 128.5, 128.1, 127.3, 125.1, 121.2, 112.9, 106.6, 93.8, 93.8, 91.3, 70.5, 55.7, 55.7; IR (thin film, neat) νmax 1620, 1595, 1553, 1452, 1344, 1213, 1107, 984, 816, 760 cm-1; LR-MS (Low-Resolution Mass Spectroscopy) (FAB+) *m*/*z* 391 (M + H<sup>+</sup>); HR-MS (High-Resolution Mass Spectroscopy) (FAB+) calculated for C24H23O5 (M + H<sup>+</sup>) 391.1545; observed 391.1541.

*Oleracone E*. (3). To a solution of chalcone 6 (500 mg, 1.28 mmol) in ethyl alcohol (10 mL), catalytic amount of 5% activated palladium on carbon was added at room temperature. After stirring for 48 h under H2 atmosphere, the reaction mixture was filtered through a pad of Celite and concentrated in vacuo. Purification of the concentrated residue by flash column chromatography (EtOAc : *n*-Hexane = 1 : 10 to 1 : 3) afforded 340 mg (88%) of oleracone E (3) as a yellowish powder. The spectral data of 3 were consistent with previous data (Table S1). m.p.: 137–138 ◦C; Rf = 0.20 (EtOAc/*n*-Hexane = 1:5); 1H NMR (500 MHz, DMSO-d6) δ 13.63 (brs, 1H), 9.30 (brs, 1H), 7.06 (dd, 1H, *J* = 1.5, 7.4 Hz), 6.99 (brtd, 1H, *J* = 1.6, 7.7 Hz), 6.77(dd, 1H, *J* = 1.0, 8.0 Hz), 6.70 (td, 1H, *J* = 1.0, 7.4 Hz), 6.11 (d, 1H, *J* = 2.4 Hz), 6.09 (d, 1H, *J* = 2.4 Hz), 3.82 (s, 3H), 3.80 (s, 3H), 3.20 (brt, 2H, *J* = 7.7 Hz), 2.81 (brt, 2H, *J* = 7.7 Hz); 13C NMR (200 MHz, DMSO-d6) δ 205.4, 166.1, 166.0, 162.9, 155.5, 130.3, 127.7, 127.5, 119.5, 115.3, 106.0, 94.2, 91.2, 56.4, 56.1, 43.9, 25.5; IR (thin film, neat) νmax 1618, 1578, 1489, 1462, 1418, 1362, 1204, 1109, 999, 829, 758 cm-1; LR-MS (FAB+) *m*/*z* 303 (M + H<sup>+</sup>); HR-MS (FAB+) calculated for C17H19O5 (M + H<sup>+</sup>) 303.1232; observed 303.1226.

*Oleracone F*. (2). *<sup>N</sup>*,*<sup>N</sup>*-Dmethylformamide dimethyl acetal (0.053 mL, 0.40 mmol) was added to a solution of oleracone E (3) (100 mg, 0.33 mmol) in toluene (5.5 mL) at room temperature. The reaction mixture was refluxed for 2 h, and then cooled to room temperature. The reaction mixture was concentrated in vacuo. Purification of the concentrated residue by flash column chromatography (EtOAc : *n*-Hexane = 1 : 2) afforded 93 mg (90%) of oleracone F (2) as a yellow powder. The spectral data of 2 were consistent with previous data (Table S2). m.p.: 224–225 ◦C; Rf = 0.23 (EtOAc/*n*-Hexane = 1:2); 1H NMR (500 MHz, DMSO-d6) δ 9.46 (s, 1H), 7.88 (s, 1H), 7.07 (dd, 1H, *J* = 1.5, 7.5 Hz), 7.01 (brtd, 1H, *J* = 1.6, 7.7 Hz), 6.78 (dd, 1H, *J* = 1.0, 8.0 Hz), 6.70 (brtd, 1H, *J* = 1.1, 7.4 Hz), 6.61 (d, 1H, *J* = 2.3 Hz), 6.48 (d, 1H, *J* = 2.3 Hz), 3.86 (s, 3H), 3.81 (s, 3H), 3.52 (s, 2H); 13C NMR (200 MHz, DMSO-d6) δ 175.8, 164.1, 160.9, 160.0, 155.4, 151.9, 130.5, 127.9, 125.7, 123.8, 119.6, 115.6, 108.7, 96.4, 93.3, 56.5, 56.3, 25.6; IR (thin film, neat) νmax 1643, 1595, 1566, 1454, 1373, 1207, 1152, 1078, 824, 752 cm-1; LR-MS (FAB+) *m*/*z* 313 (M + H<sup>+</sup>); HR-MS (FAB+) calculated for C18H17O5 (M + H<sup>+</sup>) 313.1076; observed 313.1078.

*Oleracone D* (1). To a solution of oleracone F (2) (150 mg, 0.48 mmol) in methylene chloride (5 mL), 1.92 mL of BCl3 (1 M solution in CH2Cl2, 1.92 mmol) was slowly added at 0 ◦C. After stirring for 1 h at the same temperature, the reaction mixture was quenched with H2O, diluted with methylene chloride, stirred for an additional 1 h, and extracted with methylene chloride. The combined organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo. Purification of the concentrated residue by flash column chromatography (EtOAc : *n*-Hexane = 1:5) afforded 114 mg (80%) of oleracone D (1) as a yellowish powder. The spectral data of 1 were consistent with previous data (Table S3). m.p.: 154–155 ◦C; Rf = 0.31 (EtOAc : *n*-Hexane = 1 : 5); 1H NMR (500 MHz, DMSO-d6) δ 12.76 (s, 1H), 9.47 (brs, 1H), 8.06 (s, 1H), 7.08 (dd, 1H, *J* = 1.4, 7.5 Hz), 7.03 (brtd, 1H, *J* = 1.6, 7.7 Hz), 6.81 (dd, 1H, *J* = 0.8, 8.0 Hz), 6.71 (brtd, 1H, *J* = 1.4, 7.4 Hz), 6.61 (d, 1H, *J* = 2.3 Hz), 6.38 (d, 1H, *J* = 2.3 Hz), 3.84 (s, 3H), 3.61 (s, 2H); 13C NMR (200 MHz, DMSO-d6) δ 181.6, 165.6, 161.6, 158.2, 155.4, 155.3, 130.4, 128.0, 125.0, 121.4, 119.5, 115.4, 105.5, 98.4, 92.8, 56.4, 25.0; IR (thin film, neat) νmax 1647, 1585, 1510, 1435, 1368, 1240, 1163, 1051, 822, 754 cm-1; LR-MS (FAB+) *m*/*z* 299 (M + H<sup>+</sup>); HR-MS (FAB+) calculated for C17H15O5 (M + H<sup>+</sup>) 299.0919; observed 299.0915.
