M. Kajjout, C. Rolando / Tetrahedron 67 (2011) 4731e4741
4739
17. Compound 17 was prepared by benzylation of compound 16
under standard conditions (1.3 equiv of benzyl bromide and
1.5 equiv of potassium carbonate in DMF at room temperature for
12 h). (85% yield). Mp 92e96 ꢀC. 1H NMR (CDCl3): 1.99 (s, 3H), 2.02
(s, 3H), 2.07 (s, 3H), 2.09 (s, 3H), 3.92 (m, 1H), 4.18 (m, 2H), 5.01 (s,
2H), 5.06 (s, 2H), 5.11e5.36 (m, 3H), 5.17 (d, J¼7.0 Hz, 1H), 6.37 (d,
J¼2.2 Hz, 1H), 6.47 (d, J¼2.2 Hz, 1H), 6.87 (d, J¼8.3 Hz, 1H), 7.54 (dd,
J¼8.3, 1.7 Hz, 1H), 7.46 (d, J¼1.7 Hz, 1H), 7.06e7.60 (m, 20H). 13C
NMR (CDCl3): 20.3, 20.4, 20.6, 20.9, 61.9, 68.2, 70.5, 72.1, 72.4, 72.7,
94.1, 98.2, 99.3, 108.3, 109.2, 117.9, 124.0, 124.2, 126.2, 127.4, 128.2,
128.3, 128.4, 128.9, 129.4, 133.7, 137.3, 139.7, 147.2, 149.4, 156.6, 157.0,
162.0, 162.9, 169.6, 170.2, 170.3, 170.9, 177.4. HR-FABMS (m/z): ob-
served, 999.2852; calculated for C56H48O16Na: 999.2840 [MþNa]þ.
Elemental analysis: calculated for C36H28O7 C, 75.51; H, 4.93; O,
19.56. Observed C, 75.31; H, 5.10; O, 19.43.
4.5.2. 3,7-Bisbenzyloxy-2-(3-(2,3,4,6-tetra-O-acetyl)-b-D-glucopyr-
anosyloxy-4-benzyloxyphenyl)-5-hydroxyl-4H-chromen-4-one
2120. To a solution of compound 4 (1.00 g, 1.75 mmol) and TDA
(0.48 g, 3.5 mmol), in 40 ml of saturated K2CO3 aqueous, aceto-
bromoglucose (1.1 g, 2.7 mmol) dissolved in CH2Cl2 (40 ml) was
added under argon. The mixture reaction was agitated for 24 h. The
aqueous layer was extracted with CH2Cl2 (60 ml). The organic layer
was washed successively with NaOH 0.5% (50 ml), water (50 ml),
and 50 ml of HCl 2% (neutral pH). The residue obtained after
evaporation of the solvent was purified by flash column chroma-
tography using a mixture of CH2Cl2/EtOAc (70:30) as eluent (1.10 g,
70% yield). 1H NMR (CDCl3): 1.96 (s, 3H), 2.01 (s, 3H), 2.05 (s, 3H),
2.13 (s, 3H), 3.12 (m, 1H), 4.07 (m, 2H), 5.05 (s, 2H), 5.12 (s, 2H), 5.18
(s, 2H), 5.05e5.35 (m, 3H), 4.81 (d, J¼7.5 Hz, 1H), 6.65 (d, J¼2.0 Hz,
1H), 6.85 (d, J¼2.0 Hz, 1H), 6.95 (d, J¼8.3 Hz, 1H), 7.58 (dd, J¼8.3,
1.7 Hz, 1H), 7.74 (d, J¼1.7 Hz, 1H), 7.18e7.52 (m, 15H). 13C NMR
(CDCl3): 20.8, 20.9, 21.6, 61.9, 68.3, 70.8, 71.1 71.4, 72.1, 72.9, 74.2,
94.0, 99.2, 100.2, 106.2, 114.9, 119.5, 122.8, 124.9, 127.2, 127.4, 127.9,
128.2, 128.3, 128.5, 128.6, 128.7, 128.8, 128.9, 129.0, 135.7, 135.8,
136.4, 137.6, 139.3, 145.6, 147.9, 156.7, 162.0, 164.4, 169.8, 169.9,
170.6, 171.2, 178.9. HR-FABMS (m/z): observed, 925.2671; calculated
for C50H46O16Na, 925.2668 [MþNa]þ.
4.4.4. 2-(2,2-Diphenyl-benzo[1,3]dioxol-5-yl)-3,5-bisbenzyloxy 7-
b-
D-glucopyranosyloxy-4H-chromen-4-one 18. Compound 17 (500 mg,
0.51 mmol) was dissolved in 40 ml of a mixture MeOH/THF (50:50).
A solution of sodium methylate prepared from 10 mg of sodium
metal in methanol (10 ml) was added at room temperature. When
the deprotection was completed, the solution was neutralized by
adding 2.0 g of an ion-exchange resin (Hþ form). The agitation was
maintained for 30 min, then the resin was filtered. The MeOH was
eliminated by vacuum evaporation, at room temperature. (350 mg,
85% yield). Mp 140e144 ꢀC. 1H NMR (CDCl3): 3.15 (m, 1H),
3.28e3.62 (m, 5H), 4.76 (d, J¼6.7 Hz, 1H), 5.05 (s, 2H), 5.12 (s, 2H),
6.33 (d, J¼2.2 Hz, 1H), 6.43 (d, J¼2.2 Hz, 1H), 6.93 (d, J¼8.3 Hz, 1H),
7.12e7.77 (m, 22H). 13C NMR (CDCl3): 61.4, 68.9, 70.2, 71.7, 72.1,
73.4, 76.0, 94.8, 98.4, 107.4, 108.7, 109.1, 117.9, 123.9, 124.2, 126.3,
126.3, 126.6, 127.6, 127.8, 128.4, 128.5, 128.6, 128.8, 129.4, 136.0,
137.7, 139.6, 147.0, 149.3, 155.1, 158.7, 159.7, 162.7, 173.1. HR-FABMS
(m/z): observed, 831.2403; calculated for C49H40O12Na, 831.2417
[MþNa]þ.
4.5.3. 2-(3-(2,3,4,6-Tetra-O-acetyl)-b-D-glucopyranosyloxy-4-benzy-
loxyphenyl)-3,5,7-tribenzyloxy-4H-chromen-4-one 22. Compound
22 was prepared by benzylation of compound 21 under standard
conditions (1.3 equiv of benzyl bromide and 1.5 equiv of potassium
carbonate in DMF at room temperature for 12 h). (90% yield). 1H
NMR (CDCl3): 1.97 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 2.09 (s, 3H), 3.13
(m, 1H), 4.12 (m, 2H), 5.22 (s, 2H), 5.15 (s, 2H), 5.10 (s, 2H) 5.21 (s,
2H), 5.07e5.30 (m, 3H), 4.83 (d, J¼7.5 Hz,1H), 6.65 (d, J¼2.1 Hz,1H),
6.85 (d, J¼2.1 Hz, 1H), 6.92 (d, J¼8.1 Hz, 1H), 7.58 (dd, J¼8.1, 1.8 Hz,
1H), 7.74 (d, J¼1.8 Hz, 1H), 7.18e7.52 (m, 20H). 13C NMR (CDCl3):
20.5, 20.6, 20.7, 20.8, 61.0, 66.4, 68.1, 70.5, 70.8, 71.5, 73.1, 74.2, 74.6,
93.9, 98.2, 107.8, 113.7, 117.5, 123.5, 124.0, 127.3, 127.5, 127.7, 128.2,
128.5, 128.7, 128.9, 129.0, 129.2, 129.6, 135.7, 136.4, 137.4, 139.6,
140.3, 146.2, 150.6, 152.7, 159.0, 159.8, 162.9, 169.3, 169.6, 170.3,
170.7, 173.8. ESI-MS (m/z): observed, 1015.3; calculated for
C57H52O16Na, 1015.32 [MþNa]þ.
4.4.5. Quercetin 7-O-b-D
-glucopyranoside 1920,48. Compound 19 was
synthesized according to the procedure reported for 9. (78% yield).
1H NMR (DMSO-d6): 3,12e3.67 (m, 6H), 4.98 (d, J¼6.7 Hz, 1H), 6.37
(d, J¼2.2 Hz, 1H), 6.58 (d, J¼2.2 Hz, 1H), 6.86 (d, J¼8.5 Hz, 1H), 7.49
(dd, J¼8.5, 1.7 Hz, 1H), 7.64 (d, J¼1.7 Hz, 1H). 13C NMR (CD3OD): 61.0,
69.3, 72.9, 75.9, 77.0, 94.6, 99.0, 100.1, 104.9, 115.1, 115.9, 120.1, 122.0,
136.0, 144.7, 147.4, 147.7, 157.4, 160.1, 162.1, 175.1. HR-FABMS (m/z):
observed, 465.1040; calculated for C21H21O12, 465.1033 [MþH]þ.
4.4.6. Quercetin-7-O-b-D-glucuronide 20. Compound 20 was syn-
thesized according to the procedure reported for 10. (65% yield) 1H
NMR (CD3OD): 3.25e3.73 (m, 3H), 4.08 (d, J¼9.2 Hz, 1H), 5.12 (d,
J¼6.7 Hz, 1H), 6.42 (d, J¼2.2 Hz, 1H), 6.62 (d, J¼2.2 Hz, 1H), 6.85 (d,
J¼8.5 Hz, 1H), 7.61 (dd, J¼8.5, 1.8 Hz, 1H), 7.69 (d, J¼1.8 Hz, 1H). 13C
NMR (CD3OD): 73.2, 74.5, 76.5, 77.4, 95.7, 100.4, 105.1, 106.3, 116.1,
116.3,122.0,123.9,137.7,146.2,148.7,157.6,162.0,162.9,164.3,174.8,
177.4. HR-FABMS (m/z): observed: 479.0797; calculated for
C21H19O13, 479.0826 [MþH]þ.
4.5.4. 2-(3-b-D-Glucopyranosyloxy-4-benzyloxyphenyl)-3,5,7-tri-
benzyloxy-4H-chromen-4-one 23. Compound 22 (800 mg, 0.81
mmol) was dissolved in 40 ml of a mixture MeOH/THF (50:50).
A solution sodium methylate prepared from 10 mg of sodium metal
in methanol (15 ml) was added at room temperature. When the
deprotection was completed, the solution was neutralized by
adding 2.0 g of an ion-exchange resin (Hþ form). The agitation was
maintained for 30 min, then the resin was filtered. The MeOH was
eliminated by vacuum evaporation, at room temperature. (565 mg
85% yield). Mp 144e147 ꢀC. 1H NMR (CDCl3): 3.02e3.82 (m, 4H),
4.11 (m, 2H), 4.83 (d, J¼7.5 Hz, 1H), 5.05 (s, 2H), 5.09 (s, 2H), 5.12 (s,
2H) 5.18 (s, 2H), 6.59 (d, J¼2.1 Hz,1H), 6.82 (d, J¼2.1 Hz,1H), 6.95 (d,
J¼8.1 Hz, 1H), 7.61 (dd, J¼8.1, 1.8 Hz, 1H), 7.77 (d, J¼1.8 Hz, 1H),
7.18e7.52 (m, 20H). 13C NMR (CDCl3): 60.8, 70.5, 71.1, 71.2, 72.7,
73.2, 74.1, 76.7, 77.2, 94.2, 99.1,100.9, 108.9, 114.2,115.8, 123.0, 123.2,
126.8, 127.4, 127.7, 128.1, 128.3, 128.5, 128.7, 128.9, 129.1, 136.5,
136.8, 136.9, 138.9, 147.0, 149.8, 154.2, 158.1, 159.1, 163.0, 172.3. HR-
FABMS (m/z): observed 847.2745; calculated for C49H44O12Na,
847.2730 [MþNa]þ.
4.5. Synthesis of quercetin 30-O-
b-D-glucuronide 25
4.5.1. 3,7-Bisbenzyloxy-2-(4-benzyloxyphenyl)-5-hydroxy-4H-chro-
men-4-one 420,26,50. Compound 4 was prepared by benzylation of
quercetin under classical conditions (3.5 equiv of benzyl bromide
and 3.5 equiv of potassium carbonate in DMF at room temperature
for 12 h). (20% yield). Mp 150e152 ꢀC (lit.50 148e150 ꢀC; lit.26
155 ꢀC). 1H NMR (CDCl3): 5.03 (s, 2H), 5.12 (s, 2H), 5.18 (s, 2H),
6.41 (d, J¼2.1 Hz, 1H), 6.50 (d, J¼2.1 Hz, 1H), 6.94 (d, J¼8.7 Hz, 1H),
7.21e7.47 (m, 15H), 7.70 (dd, J¼8.7, 2.1 Hz, 1H), 7.72 (d, J¼2.1 Hz,
1H). 13C NMR (CDCl3): 70.4, 71.02, 74.04, 93.02, 98.72, 106.1, 111.6,
115.1,121.9,123.8,127.5,127.9,128.2,128.3,128.6, 128.7, 128.9, 135.7,
135.8, 136.5, 137.6, 145.6, 148.0, 156.3, 156.7, 161.9, 164.4, 178.8.
4.5.5. Quercetin 30-O- -glucopyranoside 2420,48. Compound 24
b-D
was synthesized according to the procedure reported for 9. (85%
yield). 1H NMR (DMSO-d6): 3.15e3.77 (m, 6H), 4.75 (d, J¼6.7 Hz,