OMe), 3.95–4.02 (1 H, m, 3-H), 4.63 (1 H, d, J 8.2, 2-H), 4.99
(2 H, s, CH2-Bn), 5.02 (2 H, s, CH2-Bn), 5.15 (2 H, s, CH2-Bn),
6.21 (1 H, d, J 2.2, 8-H), 6.27 (1 H, d, J 2.2, 6-H), 6.91 (1 H, d,
J 7.9, 5Ј-H), 6.95 (1 H, dd, J 7.9 and 1.8, 6Ј-H), 7.02 (1 H, d,
J 1.8, 2Ј-H), 7.27–7.43 (15 H, m, Ph); δC (75 MHz, CDCl3) 27.6,
56.1, 68.2, 69.9, 70.1, 71.0, 81.6, 93.8, 94.3, 102.3, 111.8, 112.8,
120.5, 127.1, 127.5, 127.9, 128.5, 128.6, 130.0, 136.8, 148.9,
150.1, 155.3, 157.8, 158.8; m/z (EI, 70 eV) 574 (Mϩ, 60%), 319
(100), 165 (43), 91 (95); m/z (CI, NH3) 575 (100%), 485 (26), 274
(47); HR m/z (EI) 574.2347 1.4 ppm C37H34O6.
Synthesis of trimethylated catechin derivatives 24 and 25
The final deprotection of compounds 23a,b was carried out as
described previously for compounds 18a,b. After purification
by flash column chromatography with AcOEt–hexane (50 : 50)
as eluent, a mixture of compounds 24 and 25 was separated by
preparative HPLC. HPLC separations of the two trimethylated
analogues were achieved on a 250 × 4.6 mm id column packed
with 5 µm Hypersil ODS C18 stationary phase. The mobile
phase consisted of acetonitrile–methanol 38 : 62, and with
0.2% formic acid. The column eluent was directed to a UV
detector set at 280 nm.
Synthesis of 4Ј-methylcatechin 21 and 3Ј-methylcatechin 22
(2R,3S)-5,7-Dimethoxy-2-(4Ј-hydroxy-3Ј-methoxyphenyl)-
chroman-3-ol (24). Yield 35%; mp 157–158 ЊC; [α]2D0 Ϫ12.5Њ
(c 0.15, MeOH); δH (300 MHz, CDCl3) 2.58 (1 H, dd, J 16.2
and 9.0, 4a-H), 3.07 (1 H, dd, J 16.2 and 5.8, 4b-H), 3.74 (3H,
s, OMe), 3.80 (3 H, s, OMe), 3.90 (3 H, s, OMe), 4.01–4.08
(1 H, m, 3-H), 4.63 (1 H, d, J 8.4, 2-H), 6.10 (1 H, d, J 2.2,
8-H), 6.13 (1 H, d, J 2.2, 6-H), 6.93–6.97 (3 H, br d, 6Ј-H and
5Ј-H and 2Ј-H); δC (75 MHz, CDCl3) 27.7, 55.4, 55.5, 55.9,
68.3, 81.9, 91.9, 93.0, 101.7, 109.4, 114.6, 120.6, 129.6, 146.1,
146.9, 155.3, 158.7, 159.7.
The final deprotection of compounds 19 and 20 was carried out
as described previously for 3Ј,4Ј-dimethylcatechin 14.
(2R,3S)-2-(4Ј-Hydroxy-3Ј-methoxyphenyl)chroman-3,5,7-triol
(21).14a,16b,29c,30 Yield 85%; mp 186–187 ЊC; [α]2D0 ϩ4.0Њ (c 0.28,
acetone); δH (300 MHz, [D6]acetone) 2.52 (1 H, dd, J 16.0 and
8.8, 4a-H), 2.97 (1 H, dd, J 16.0 and 5.5, 4b-H), 3.84 (3H, s,
OMe), 3.94–4.05 (1 H, m, 3-H), 4.56 (1 H, d, J 8.1, 2-H), 5.87
(1 H, d, J 2.1, 8-H), 6.03 (1 H, d, J 2.1, 6-H), 6.80 (1 H, d, J 8.1,
6Ј-H), 6.88 (1 H, dd, J 8.1 and 1.7, 5Ј-H), 7.02 (1 H, d, J 1.7,
2Ј-H); δC (75 MHz, [D6]acetone) 27.9, 56.1, 68.0, 82.9, 95.4,
96.0, 100.7, 111.7, 115.3, 121.4, 131.7, 147.2, 148.0, 156.9,
157.1, 157.7; m/z (EI, 70 eV) 304 (59), 166 (100), 139 (76), 128
(72), 77 (73); m/z (CI, NH3) 305 (100); HR m/z (EI) 304.0948
0.4 ppm C16H16O6.
(2R,3S)-5,7-Dimethoxy-2-(3Ј-hydroxy-4Ј-methoxyphenyl)-
chroman-3-ol (25).30a Yield 40%; mp 154–155 ЊC; [α]2D0 Ϫ8.0Њ
(c 1.00, acetone); δH (300 MHz, CDCl3) 2.58 (1 H, dd, J 16.3
and 8.8, 4a-H), 3.02 (1 H, dd, J 16.3 and 5.5, 4b-H), 3.74
(3H, s, OMe), 3.79 (3 H, s, OMe), 3.90 (3 H, s, OMe), 4.02–
4.12 (1 H, m, 3-H), 4.66 (1 H, d, J 8.1, 2-H), 6.09 (1 H, d, J 2.3,
8-H), 6.12 (1 H, d, J 2.3, 6-H), 6.87 (1 H, d, J 8.2, 5Ј-H), 6.93
(1 H, dd, J 8.2 and 1.9, 6Ј-H), 7.02 (1 H, d, J 1.9, 2Ј-H);
δC (75 MHz, CDCl3) 27.3, 55.3, 55.5, 56.0, 68.1, 81.5, 91.9,
93.0, 101.5, 110.7, 113.1, 119.2, 131.0, 146.0, 146.9, 155.2,
158.7, 159.7.
(2R,3S)-2-(3Ј-Hydroxy-4Ј-methoxyphenyl)chroman-3,5,7-triol
(22).15b,28,30a,30b Yield 87%; mp 152–153 ЊC (Found: C, 59.25; H,
5.82%; C16H16O6ؒH2O requires C, 59.62; H, 5.63%; [α]2D0 ϩ20.6Њ
(c 0.65, acetone); δH (300 MHz, [D6]acetone) 2.52 (1 H, dd,
J 16.0 and 8.2, 4a-H), 2.91 (1 H, dd, J 16.0 and 5.4, 4b-H), 3.83
(3H, s, OMe), 3.97–4.03 (1 H, m, 3-H), 4.59 (1 H, d, J 7.5, 2-H),
5.88 (1 H, d, J 2.0, 8-H), 6.02 (1 H, d, J 2.0, 6-H), 6.84 (1 H, dd,
J 8.3 and 1.8, 5Ј-H), 6.91 (1 H, d, J 8.3, 6Ј-H), 6. 92 (1 H, d,
J 1.8, 2Ј-H); δC (75 MHz, [D6]acetone) 29.0, 56.2, 68.2, 82.5,
95.4, 96.0, 100.5, 111.9, 114.9, 119.6, 133.4, 147.1, 148.0, 156.8,
157.1, 157.7; m/z (EI, 70 eV) 304 (Mϩ, 100%), 166 (99), 139 (95);
m/z (CI, NH3) 305 (100%); HR m/z (EI) 304.0951 1.3 ppm
C16H16O6.
Acknowledgements
We thank Dr Yves Plancke for the purification of the methyl-
ated catechin isomers and Dr Jean-Michel Wieruszeski for the
NOE, NOESY and ROESY experiments. The authors grate-
fully acknowledge the reviewers for their suggestions and for
the careful reading of the manuscript. This work was supported
by the European Community (European Contract QLK1-
CT-199–00505 POLYBIND) and the Conseil Régional Nord,
Pas-de-Calais.
Synthesis of the compounds 23a,b
To a stirred solution of compounds 16a,b (0.5 g, 1.12 mmol)
in acetone (30 mL) was added potassium carbonate (0.16 g,
4.48 mmol) and methyl iodide (0.28 mL, 4.48 mmol). The reac-
tion was stirred at room temperature for 12 h. Acetone was
removed under vacuum and the resulting mixture was washed
with water (20 mL). The aqueous layer was extracted with
AcOEt (3 × 30 mL) and dried over MgSO4. Evaporation of
the solvent furnished on oily product which was purified by
flash column chromatography using AcOEt–hexane (40 : 60) as
eluent to give a 50 : 50 mixture of products 23a,b.
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