Synthesis of Alkyl Quercetin Derivatives
Mihyang Kim, Youngrong Park, Sooyoung Cho, Supawadee Burapan and Jaehong Han*
1. NMR data of the new quercetin derivatives…………………………………………….. 2
2. Experimental details ……………………………………………………………………. 3
3. Physical property ……………………………………………………………………… 12
1
1. NMR data of the new quercetin derivatives
Table S1. 1H NMR (600 MHz) and 13C NMR (150 MHz) data of the new quercetin alkyl
ether derivatives (δ ppm, CDCl3)
Compound
5
8
9
10
11
H6
6.32 (d, 2.2Hz)
6.32 (d, 1.9Hz)
6.32 (d, 2.0Hz)
6.32 (d, 2.2Hz)
6.24 (d, 2.6Hz)
H8
6.40 (d, 2.2Hz)
6.42 (d, 1.9Hz)
6.42 (d, 2.0Hz)
6.42 (d, 2.2Hz)
6.40 (d, 2.6Hz)
H2’
7.72 (d, 2.2Hz)
7.70 (m)
7.70 (d, 2.0Hz)
7.69 (d, 2.0Hz)
7.74 (d, 2.1Hz)
H5’
6.92 (d, 8.3Hz)
6.92 (d, 9.0Hz)
6.82 (d, 8.6Hz)
6.93 (d, 8.5Hz)
6.93 (ddd,
8.8Hz, 2.1Hz,
0.9Hz)
H6’
7.70 (dd,
2.2Hz, 8.3Hz)
7.70 (m)
7.68 (dd,
2.0Hz, 8.6Hz)
7.69 (dd,
2.0Hz, 8.5Hz)
7.73 (m)
3-OH
-
-
-
-
5.71
5-OH
12.66
12.66
12.68
12.66
11.79
3’-OH
5.77
5.75
-
5.70
-
R
1.34-1.50
(3CH3), 4.084.20 (3CH2)
0.96-1.08
(3CH3), 1.761.89 (3CH2),
3.95-4.09
(3CH2)
0.95-1.07
(4CH3), 1.751.89 (4CH2),
3.94-4.03
(4CH2)
0.91-1.01
(3CH3), 1.431.53 (3CH2),
1.72-1.85
(3CH2), 3.954.09 (3CH2)
0.67-1.02
(3CH3), 1.131.87 (6CH2),
3.99-4.11
(3CH2)
C2
155.8
155.8
156.1
155.8
165.1
C3
138.0
138.2
138.0
138.3
-
C4
178.9
179.0
178.9
178.9
169.7
C5
161.9
161.9
162.0
161.9
164.3
C6
98.1
98.2
98.1
98.2
99.8
C7
164.7
165.0
164.9
164.9
164.7
C8
92.4
92.4
92.6
92.5
99.8
C4a
105.9
106.0
105.9
105.9
103.6
C8a
156.7
156.7
156.7
156.7
152.6
C1’
123.6
123.6
123.0
123.6
123.6
C2’
110.9
111.0
112.5
111.0
110.6
C3’
145.4
145.5
151.5
145.5
145.4
C4’
147.9
148.1
148.5
148.0
150.4
C5’
114.4
114.5
114.2
114.4
116.1
C6’
121.6
121.6
122.3
121.6
122.4
R
14.5, 14.8,
15.5, 64.2,
64.6, 68.5
10.4 (3C), 22.3,
22.4, 23.3,
70.1, 70.5, 74.5
10.4 (3C), 10.5,
22.3, 22.5,
22.6, 23.4,
70.1, 70.4,
71.0, 74.5
13.8 (3C), 19.1,
19.2 (2C), 31.1
(2C), 32.1,
68.3, 68.8, 72.6
13.3, 13.7,
13.8, 18.9, 19.1
(2C), 30.1,
30.9, 31.0,
65.5, 68.2, 68.9
2
2. Experimental Details
Quercetin (97%) and benzyl bromide were purchased from Alfa Aesar (Ward Hill, MA,
USA). Potassium carbonate (99.5%), magnesium sulfate, anhydrous (99.5%), sodium
chloride (99.5%), celite 545, sea sand (15-20 mesh) and methyl iodide (99.0%) were
purchased from Samchun Chemicals (Pyeongtaek-si, Korea). Ethyl iodide purchased from
Junsei (Tokyo, Japan). 1-Bromopopane (98.0%) and 1-bromobutane (98.0%) were
purchased from TCI (Tokyo, Japan).
Progress of quercetin alkylation reaction were monitored by TLC with the solvent systems
of 2:1 or 1:1 mixture of hexanes and ethyl acetate. Visualization of the compounds on TLC
plates was commonly achieved by UV light and I2 vapor. The reaction mixture was isolated
by column chromatography or VLC (vacuum liquid chromatography) using hexanes/ethyl
acetate system or hexanes/acetone gradient. Melting point was measured by KRUSS M5000
melting point meter (Hamburg, Germany). NMR spectra were recorded on a Varian VNS
(600 MHz, California, USA). IR spectra of compounds in KBr pellet were obtained on a
Shimadzu FT-IR 8400S spectrophotometer (Tokyo, Japan). UV-vis spectra were recorded on
a Scinco S-3150 UV-Vis spectrophotometer (Seoul, Korea). ESI-MS spectra were recorded
on a Thermo LCQ fleet (Waltham, USA).
Quercetin methyl ether derivatives, 5,3’-dihydroxy-3,7,4’-trimethoxyflavone (2) and 5hydroxy-3,7,3’,4’-tetramethoxyflavone (3) To a solution of quercetin (1) (174 mg, 0.57
mmol) in DMF (20 ml) was added potassium carbonate (416 mg, 3.0 mmol, 5.3 eq) and
methyl iodide (0.17 ml, 2.75 mmol, 4.8 eq) at room temperature. After 12h reaction, the
reaction mixture was poured into water (100 ml), and the organic products were extracted
with ethyl acetate (100 ml) three times. The combined organic solution was washed with
3
brine (100 ml), dried over anhydrous MgSO4, filtered and concentrated under reduced
pressure. The crude extract was purified by column chromatography (10% ethyl acetate in
hexanes) to yield 5,3’-dihydroxy-3,7,4’-trimethoxyflavone (2, 44.5 mg, 26%) as yellow
powder, 5-hydroxy-3,7,3’,4’-tetramethoxyflavone (3, 85.5 mg, 48%) as yellow crystals, and
3,5,7,3’,4’-pentamethoxyflavone (4, 15mg, 8%) as white solids.
5,3’-Dihydroxy-3,7,4’-trimethoxyflavone (2)
Mp 168-170°C; 1H NMR (CDCl3, 600 MHz) δ 3.86 (s, 3H, -OCH3), 3.87 (s, 3H, -OCH3),
3.99 (s, 3H, -OCH3), 5.71 (s, 1H, 3’-OH), 6.40 (d, 1H, J = 2.2 Hz, 6-H), 6.44 (d, 1H, J = 2.2
Hz, 8-H), 6.97 (d, 1H, J = 8.6 Hz, 5’-H), 7.69 (d, 1H, J = 2.2Hz, 2’-H), 7.72 (dd, 1H, J =
2.2, 8.6 Hz, 6’-H), 12.63 (s, 1H, 5-OH); IR, cm-1: 1663 (C=O); UV-vis, λmax (ε M-1 cm-1,
MeOH): 255 (14300), 352 (13900); ESI-MS m/z: 345 [M+H]+.
5-Hydroxy-3,7,3’,4’-tetramethoxyflavone (3) Mp 161-162°C; 1H NMR (CDCl3, 600
MHz) δ 3.86 (s, 3H, -OCH3), 3.87 (s, 3H -OCH3),3.96(s, 3H -OCH3), 3.97(s, 3H -OCH3),
6.35 (d, 1H, J = 2.2 Hz, 6-H), 6.44 (d, 1H, J = 2.2 Hz, 8-H), 6.99 (d, 1H, J = 8.6 Hz, 5’-H),
7.68 (d, 1H, J = 2.1 Hz, 2’-H), 7.73 (dd, 1H, J = 2.1, 8.5 Hz, 6’-H), 12.63 (s, 1H, 5-OH); IR,
cm-1: 1663 (C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 252 (13000), 351 (14500); ESI-MS
m/z: 359 [M+H]+.
3,5,7,3’,4’-Pentamethoxyflavone (4) Mp 152-153°C; 1H NMR (CDCl3, 600 MHz) δ 3.87
4
(s, 3H, -OCH3), 3.89 (s, 3H, -OCH3), 3.95 (s, 9H, 3×-OCH3), 6.34 (d, 1H, J = 2.3 Hz, 6-H),
6.49 (d, 1H, J = 2.3 Hz, 8-H), 6.97 (d, 1H, J = 8.3 Hz, 5’-H), 7.69 (dd, 1H, J = 2.2 Hz, 8.3
Hz, 6’-H), 7.70 (d, 1H, J = 2.0 Hz, 2’-H); IR, cm-1: 1628 (C=O); UV-vis, λmax (ε M-1 cm-1,
MeOH): 250 (14100), 340 (16000); ESI-MS m/z: 373 [M+H]+.
Synthesis of 3,5,7,3’,4’-pentamethoxyflavone (4) To a solution of quercetin 1 (1.05 g, 3.0
mmol) in DMF (120 ml) was added potassium carbonate (12.52 g, 90.1 mmol, 30 eq) and
methyl iodide (5.7 ml, 90.6 mmol, 30 eq) at room temperature. After 3h, the reaction
mixture was poured into water (120 ml), and extracted with ethyl acetate (120 ml) three
times. The extract was washed with brine (120 ml), dried over anhydrous MgSO4, filtered
and concentrated. The crude extract was purified by VLC using hexanes and ethyl acetate to
yield 3,5,7,3’,4’-pentamethoxyflavone (4, 478mg, 43%) as white solid.
Quercetin ethyl ether derivatives, 5,3’-dihydroxy-3,7,4’-triethoxyflavone (5) and 5hydroxy-3,7,3’,4’-tetraethoxyflavone (6) To a solution of quercetin 1 (1.05 g, 3.0 mmol) in
DMF (100 ml) was added potassium carbonate (2.51 g, 18.1 mmol, 6 eq) and ethyl iodide
(1.37 ml, 16.5 mmol, 5.5 eq) at room temperature. After 12h, the reaction mixture was
poured into water (200 ml), and extracted with ethyl acetate (200 ml) five times. The extract
was washed with brine (250 ml), dried over anhydrous MgSO4, filtered and concentrated.
The crude extract was purified by column chromatography c to yield 5,3’-dihydroxy-3,7,4’triethoxyflavone (5, 654 mg, 56%) as yellow powder and 5-hydroxy-3,7,3’,4’tetraethoxyflavone (6, 215 mg, 17%) as yellow crystals.
5,3’-Dihydroxy-3,7,4’-triethoxyflavone (5) Mp 131°C. 1H NMR (CDCl3, 600 MHz) δ 1.34
(t, 3H, J = 7.0 Hz, -CH3), 1.44 (t, 3H, J = 7.0 Hz, -CH3), 1.50 (t, 3H, J = 7.0 Hz, -CH3),
4.08(q, 4H, J = 2.0, 7.0 Hz, 2×-CH2-), 4.20(q, 2H, J = 7.0 Hz, -CH2-), 5.77 (s, 1H, 3’-OH),
6.32 (d, 1H, J = 2.2 Hz, 6-H), 6.40 (d, 1H, J = 2.2 Hz, 8-H), 6.92 (d, 1H, J = 8.3 Hz, 5’-H),
5
7.70 (dd, 1H, J = 2.2, 8.6 Hz, 6’-H), 7.72 (d, 1H, J = 2.2 Hz, 2’-H), 12.66 (s, H, 5-OH); 13C
NMR (CDCl3, 150 MHz) δ 14.5, 14.8, 15.5, 64.2, 64.6, 68.5, 92.4 (C-8), 98.1 (C-6), 105.9,
110.9, 114.4, 121.6, 123.6, 138.0, 145.4, 147.9, 155.8, 156.7, 161.9, 164.7, 178.9; IR, cm-1:
1660 (C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 256 (18600), 353 (14600); ESI-MS m/z:
387 [M+H]+.
5-Hydroxy-3,7,3’,4’-tetraethoxyflavone (6) Mp 115-116 °C. 1H NMR (CDCl3, 600 MHz)
δ 1.33 (t, 3H, J = 7.0 Hz, -CH3), 1.44 (t, 3H, J = 7.0 Hz, -CH3), 1.50 (dt, 6H, J = 3.5, 7.0 Hz,
2×-CH3), 4.08 (m, 4H), 4.17 (m, 4H), 6.32 (d, 1H, J = 2.2, 6-H), 6.41 (d, 1H, J = 2.2 Hz,
8-H), 6.96 (d, 1H, J = 8.6 Hz, 5’-H), 7.69 (dd, 1H, J = 2.1, 8.6 Hz, 6’-H), 7.74 (d, 1H, J =
2.1 Hz, 2’-H), 12.68 (s, 1H, 5-OH); 13C NMR (CDCl3, 150 MHz) δ 14.6, 14.7, 14.8, 15.6,
64.2, 64.4, 64.7, 68.5, 92.5, 98.1, 105.9, 112.2, 113.6, 122.1, 123.0, 137.8, 148.1, 151.1,
156.1, 156.7, 162.0, 164.7, 178.9(C-4); IR, cm-1: 1663 (C=O); UV-vis, λmax (ε M-1 cm-1,
MeOH): 255 (16600), 352 (13700); ESI-MS m/z: 415 [M+H]+
Synthesis of 3,5,7,3’,4’-pentaethoxyflavone (7) To a solution of quercetin 1 (1.07 g, 3.0
mmol) in DMF (120 ml) was added potassium carbonate (12.57 g, 90.4 mmol, 30 eq) and
ethyl iodide (7.5 ml, 90.5 mmol, 30 eq) at room temperature. After 8h, the reaction mixture
was poured into water (120 ml), and extracted with ethyl acetate (120 ml) five times. The
extract was washed with brine (120 ml), dried over anhydrous MgSO4, filtered and
concentrated. The crude extract was purified by vacuum liquid chromatography to yield
3,5,7,3’,4’-pentaethoxyflavone (7, 875 mg, 66%) as white solid; mp 116-118 °C. 1H NMR
(CDCl3, 600 MHz) δ 1.31 (t, 3H, -CH3), 1.45 (t, 3H, -CH3), 1.48 (t, 6H, 2×-CH3), 1.54 (t,
3H, -CH3), 4.08 (p, 4H, J = 6.2, 7.0 Hz), 4.14 (m, 6H), 6.30 (d, 1H, J = 2.2 Hz, 6-H), 6.44
(d, 1H, J = 2.2 Hz, 8-H), 6.94 (d, 1H, J = 8.5 Hz, 5’-H), 7.66 (dd, 1H, J = 2.0, 8.5 Hz, 6’-H),
7.75 (d, 1H, J = 2.0 Hz, 2’-H); 13C NMR (CDCl3, 150 MHz) δ 14.6, 14.6, 14.7, 14.8, 15.7,
6
64.0, 64.4, 64.7, 65.0, 68.0, 92.8, 97.0, 109.5, 112.3, 113.7, 121.6, 123.6, 140.0, 148.0,
150.4, 152.7, 158.7, 160.3, 163.0, 174.0; IR, cm-1: 1634 (C=O); UV-vis, λmax (ε M-1 cm-1,
MeOH): 249 (22000), 341 (21000); ESI-MS m/z: 443 [M+H]+.
Synthesis of 5,3’-dihydroxy-3,7,4’-tripropoxyflavone (8) and 5-hydroxy-3,7,3’,4’tetrapropoxyflavone (9) To a solution of quercetin 1 (1.04 g, 3.0 mmol) in DMF (100 ml)
was added potassium carbonate (12.91 g, 92.9 mmol, 30 eq) and 1-bromopropane (8.3 ml,
89.9 mmol, 30 eq). After stirring at 0°C for 1h, the reaction mixture was warm up to room
temperature and stirred for 12h. After 12h, the reaction mixture was poured into water (200
ml), and extracted with ethyl acetate (200 ml) five times. The extract was washed with brine
(200 ml), dried over anhydrous MgSO4, filtered and concentrated. The crude extract was
purified by column chromatography (10% ethyl acetate in hexanes) to yield 5,3’-dihydroxy3,7,4’-tripropoxyflaovne (8, 296 mg, 23%) as yellow solid and 5-hydroxy-3,7,3’,4’tetrapropoxyflavone (9, 263 mg, 19%) as yellow solid.
5,3’-Dihydroxy-3,7,4’-tripropoxyflavone (8) Mp 138 °C. 1H NMR (CDCl3, 600 MHz) δ
0.96 (t, 3H, -CH3), 1.04 (t, 3H, -CH3), 1.08 (t, 3H, -CH3), 1.76 (m, 2H, J = 7.0 Hz), 1.83 (m,
2H, J = 7.0 Hz), 1.89 (m, 2H, J = 7.0 Hz), 3.95 (t, 2H, J = 6.8 Hz), 3.97 (t, 2H, J = 6.6 Hz),
4.09 (t, 2H, J = 6.5 Hz), 5.75 (s, 1H, 3’-OH), 6.32 (d, 1H, J = 1.9 Hz, 6-H), 6.42 (d, 1H, J =
1.9 Hz, 8-H), 6.92 (d, 1H, J = 9.0 Hz, 5’-H), 7.70 (m, 2H,2’-H, 6’-H), 12.66 (s, 1H, 5-OH);
C NMR (CDCl3, 150 MHz) δ 10.4, 10.4, 10.4, 22.3, 22.4, 23.3, 70.1, 70.5, 74.5,92.4, 98.2,
13
106.0, 111.0, 114.5, 121.6, 123.6, 138.2, 145.5, 148.1, 155.8, 156.7, 161.9, 165.0, 179.0;
IR, cm-1: 1663 (C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 257 (12500), 354 (9700).
5-Hydroxy-3,7,3’,4’-tetrapropoxyflavone (9) Mp 103-105 °C. 1H NMR (CDCl3, 600
MHz) δ 0.95 (t, 3H, -CH3), 1.03(t, 3H, -CH3), 1.07 (t, 6H, -CH3), 1.75 (q, 2H, J = 7.2 Hz),
1.83 (q, 2H, J = 7.2 Hz) 1.89 (m, 4H), 3.94 (t, 2H), 3.98 (t, 2H), 4.03 (m, 4H,), 6.32 (d, 1H, J
7
= 2.0 Hz, 6-H), 6.42 (d, 1H, J = 2.0 Hz, 8-H), 6.82 (d, 1H, J = 8.6 Hz, 5’-H), 7.68 (dd, 1H, J
= 2.0, 8.6 Hz, 6’-H), 7.70 (d, 1H, J = 2’- Hz), 12.68 (s, 1H, 5-OH); 13C NMR (CDCl3, 150
MHz) δ 10.4, 10.4, 10.4, 10.5, 22.3, 22.5, 22.6, 23.4, 70.1, 70.4, 71.0, 74.5,92.6, 98.1, 105.9,
112.5, 114.2, 122.3, 123.0, 138.0, 148.5, 151.5, 156.1, 156.7, 162.0, 164.9, 178.9; IR, cm-1:
1663 (C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 258 (20000), 300 (11300), 352 (11700);
ESI-MS m/z: 471 [M+H]+.
Synthesis of 5,3’-dihydroxy-3,7,4’-tributoxyflavone (10) and 3,5-dihydroxy-7,3’,4’tributoxyflavone (11)
To a solution of quercetin 1 (1.05 g, 3.0 mmol) in DMF (100 ml) was added potassium
carbonate (2.52 g,18.1mmol, 6eq) and 1-bromobutane (1.8 ml, 16.4mmol, 5.5eq). After
stirring at 0°C for 1h, the reaction mixture was warm up to room temperature and stirred for
24h. After 24h, the reaction mixture was poured into water (200 ml), and extracted with
ethyl acetate (200 ml) five times. The extract was washed with brine (200 ml), dried over
anhydrous MgSO4, filtered and concentrated. The crude extract was purified by column
chromatography (10% ethyl acetate in hexanes) and vacuum liquid chromatography using
hexanes and acetone to yield 5,3’-dihydroxy-3,7,4’-tributoxyflavone (10, 48.2 mg, 3%) as
yellow solid and 3,5-dihydroxy-7,3’,4’-tributoxyflavone (11, 31.9 mg, 2%) as white crystal.
5,3’-Dihydroxy-3,7,4’-tributoxyflavone (10) Mp 83-85 °C. 1H NMR (CDCl3, 600 MHz) δ
0.91 (t, 3H, -CH3), 0.99 (t, 3H, -CH3), 1.01 (t, 3H, -CH3), 1.43 (m, 2H), 1.50 (m, 2H), 1.53
(m, 2H), 1.72 (m, 2H), 1.79 (m, 2H), 1.85 (m, 2H), 5.70 (s, 1H, 3’-OH), 6.32(d, 1H, J = 2.2
Hz, 6-H), 6.42 (d, 1H, J = 2.2 Hz, 8-H), 6.93 (d, 1H, J = 8.6 Hz, 5’-H), 7.69 (d, 1H, J = 2.0
Hz, 2’-H), 7.70 (dd, 1H, J = 2.2, 8.5 Hz, 6’-H), 12.66 (s, 1H, 5-OH); 13C NMR (CDCl3, 150
MHz) δ 13.8, 13.8, 13.8, 19.1, 19.2, 19.2, 31.1, 31.1, 32.1, 68.3, 68.8, 72.6, 92.46, 98.2,
105.9, 111.0, 114.4, 121.6, 123.6, 138.3, 145.5, 148.0, 155.8, 156.7, 161.9, 164.9, 178.9; IR,
cm-1: 1662 (C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 256 (16000), 353 (13400).
8
3,5-Dihydroxy-7,3’,4’-tributoxyflavone (11) Mp 101-102 °C. 1H NMR (CDCl3, 600 MHz)
δ 0.67 (t, 3H, -CH3), 0.97 (t, 3H, -CH3), 1.02 (t, 3H, -CH3), 1.13 (m, 2H, -CH2-), 1.23 (m,
2H, -CH2-), 1.48 (m, 2H, -CH2-), 1.53 (m, 2H, -CH2-), 1.76 (m, 2H, -CH2-), 1.87 (m, 2H, CH2-), 3.99 (t, 2H, -OCH2-), 4.11 (t, 2H, -OCH2-), 4.16 (t, 2H, -OCH2-), 5.71 (s, 1H, -OH),
6.24 (d, 1H, J = 2.5 Hz, 6-H), 6.40 (d, 1H, J = 2.6 Hz, 8-H), 6.93 (dd, 1H, J = 1.3, 7.5 Hz),
7.74 (d, 1H, J = 0.8 Hz), 7.75 (dd, 1H, J = 2.1, 8.3 Hz), 11.79 (s, 1H); 13C NMR (CDCl3,
150 MHz) δ 13.3, 13.7, 13.8, 18.9, 19.1, 19.1, 30.1, 30.9, 31.0, 65.5, 68.2, 68.9, 99.8, 100.5,
103.6, 110.6, 116.1, 122.4, 123.6, 145.4, 150.4, 152.6, 164.3, 164.7, 165.1, 169.7; IR, cm-1:
1743 (C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 262 (16200), 300 (9600).
Synthesis of 5,3’-dihydroxy-3,7,4’-tribenzoxyflavone (12) and 5-hydroxy-3,7,3’,4’tetrabenzoxylflavone (13)
To a solution of quercetin 1 (1.05 g, 3.0 mmol) in DMF (100 ml) was added potassium
carbonate (2.51 g, 18.0 mmol, 6 eq) and benzyl bromide (2.0 ml, 16.6 mmol, 5.5 eq). After
stirring at 0°C for 2h, the reaction mixture was warm up to room temperature and stirred for
12h. After 12h, the reaction mixture was poured into water (200 ml), and extracted with
ethyl acetate (200 ml) five times. The extract was washed with brine (250 ml), dried over
anhydrous MgSO4, filtered and concentrated. The crude extract was purified by column
chromatography (10% ethyl acetate in hexanes) to yield5,3’-dihyroxy-3,7,4’tribenzoxyflavone (12, 78.7mg, 5%) as yellow solid and 5-hydroxy-3,7,3’,4’tetrabenzoxyflavone (13, 715.6mg, 36%) as yellow solid.
5,3’-Dihydroxy-3,7,4’-tribenzoxyflavone (12) Mp 156-158 °C. 1H NMR (CDCl3, 600
MHz) δ 5.07 (s, 2H), 5.13 (s, 2H), 5.19 (s, 2H), 5.72 (s, 1H, 3’-OH), 6.44 (d, 1H, J =2.2 Hz,
6-H), 6.46 (d, 1H, J =2.2 Hz, 8-H), 6.95 (d, 1H, J =9.2 Hz, 5’-H), 7.38 (m, 15H),7.62 (d, 1H,
J =2.0 Hz, 2’-H), 7.62 (dd, 1H, J =2.2, 9,2 Hz, 6’-H), 12.69 (s, 1H, 5-OH); IR, cm-1: 1658
(C=O); 13C NMR (CDCl3, 150 MHz) δ 70.4, 71.1, 74.2, 111.5, 114.9, 121.9, 124.0, 127.4,
9
127.9, 128.1, 128.3, 128.3, 128.7, 128.7, 128.8, 128.8, 135.6, 135.8, 136.4, 145.6, 147.8,
158.3, 156.7, 162.0, 164.4, 178.8; UV-vis, λmax (ε M-1 cm-1, MeOH): 256 (15700), 352
(13600).
5-Hydroxy-3,7,3’,4’-tetrabenzoxyflavone(13) Mp 142 °C. 1H NMR (CDCl3, 600 MHz) δ
4.99 (s, 2H), 5.04 (s, 2H), 5.13 (s, 2H), 5.25 (s, 2H), 6.44(d, 1H, J =2.2 Hz, 6-H), 6.50 (d,
1H, J =2.2 Hz, 8-H), 6.96 (d, 1H, J =8.6 Hz, 5’-H), 7.34 (m, 20H), 7.55 (dd, 1H, J =2.2, 8.6
Hz, 6’-H), 7.71 (d, 1H, J =2.1 Hz, 2’-H),12.69 (s, 1H, 5-OH); 13C NMR (CDCl3, 150 MHz)
δ 70.4, 80.9, 71.1, 74.3, 127.2, 127.3, 127.4, 127.9, 128.0, 128.3, 128.3, 128.3, 128.5, 128.6,
128.7, 128.8, 135.8, 136.6, 148.2, 151.1, 156.3, 156.7, 162.1, 164.4, 178.8; IR, cm-1: 1655
(C=O); UV-vis, λmax (ε M-1 cm-1, MeOH): 256 (19300), 351 (14200).
Antioxidant activity Free radial scavenging activity of alkyl quercetin derivatives was
measured by 2,3-diphenyl-2-picryhadray (DPPH). One concentration of samples (60-250 μg
/mL) prepared in methanol.
Each concentration (50 μg /mL) was mixed with DPPH
solution (950 μL) DPPH solution and vortexed. DPPH radical scavenging activity was
measured at 516 nm. Radical scavenging activity was calculated using the following
formula:
% Inhibition = [(AB-AS)/AB]×100
AB = absorbance of the blank sample, and AS= absorbance of the sample.
Table S2. IC50 and DPPH inhibition % of alkyl quercetin derivatives.
Compound
1
2
3
4
5
6
7
8
9
IC50 (µg/mL)
5.6
-
DPPH inhibition %
97.80a
37.51b
0.55a
-0.33c
2.83a
1.80e
0.55a
1.08a
0.27d
10
10
11
12
13
Ascorbic acid
3.53a
2.88a
-3.22f
-2.22f
5.5
a. Sample concentration at DPPH inhibition %: 250µg/ml
b. Sample concentration at DPPH inhibition %: 200µg/mL
c. Sample concentration at DPPH inhibition %: 100µg/mL
d. Sample concentration at DPPH inhibition %: 140µg/mL
e. Sample concentration at DPPH inhibition %: 120µg/mL
f. Sample concentration at DPPH inhibition %:60µg/mL
Antibacterial activity of alkyl quercetin derivatives was tested by the agar well diffusion
method. Escherichia coli TISTR780, Staphyloccousaureus TISTR1466, Salmonella
typhimurium TISTR292, Enterobacteraerogenes TISTR1540, Bacillus cereus TISTR678
and Enterococcus feacalis TISTR379 were inoculated into medium by gently mixing 0.1 ml
of the 24 h fresh cultures. The antibacterial assay plates were incubated at 37 °C for 24 h.
The control and the alkyl quercetin derivatives (10 mg or 20 mg/1 mL-DMSO) were
introduced in the holes on the agar plate (6 mm diameter) (20 µL).The diameter of the zones
of inhibition around each of the wells or discs was taken as measure of the antimicrobial
activity. LB agar plate was prepared by dissolving NaCl (5 g), trypton (5 g), yeast extract
(2.5 g), and 7.5 g agar in 500 ml distilled water and sterilized by autoclaving at temperature
121 ◦C for 20 min. (for LB liquid media growing bacteria in the tube used LB without agar).
Each experiment was carried out in triplicate and the mean diameter of the inhibition zone
was reported.
Table S3. Bacterial growth inhibition zone for alkyl quercetin derivatives.
Test strain
E. Coli
TISTR780
S. aureus
TISTR1466
S. typhimurium
TISTR292
E. aerogenes
TISTR1540
1
2
3
Zone of growth inhibition (mm)
4
5
6
7
8
9 10
11
12
13
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
11
B. cereus
TISTR678
E. feacalis
TISTR379
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni
ni. No inhibiton
3. Solubility of alkyl quercetin derivatives
Table S4. Solubility table of alkyl quercetin derivatives.
THF
Ether
DCM
Chloroform
EtOAc
MeOH
EtOH
ACN
DMSO
1
◎
×
×
×
×
◎
◎
△
◎
2
◎
×
◎
○
◎
○
×
○
◎
3
◎
×
◎
◎
○
○
×
○
○
4
◎
×
◎
◎
◎
△
○
◎
○
5
◎
○
◎
◎
◎
○
○
◎
◎
6
◎
◎
◎
◎
◎
△
△
◎
○
7
◎
○
◎
◎
◎
○
○
◎
○
8
◎
◎
◎
◎
◎
○
○
◎
◎
9
◎
◎
◎
◎
◎
△
○
◎
○
10
◎
◎
◎
◎
◎
○
○
◎
◎
11
◎
◎
◎
◎
◎
○
△
◎
◎
12
◎
×
◎
◎
◎
×
×
△
◎
13
◎
×
◎
◎
○
×
×
×
○
◎: Immediately soluble
○: Soluble.
△: Sparingly soluble.
×: Rarely soluble.
12