DeriVatiVes of Catechin Gallate and Epicatechin Gallate
in enhancement at 3.90 (H3) (9.78%); 13C NMR (100 MHz, CDCl3)
161.2, 159.0, 156.6, 149.6, 149.4, 137.6, 137.5, 136.9, 136.7, 135.5,
131.9, 128.9, 128.8, 128.7, 128.5, 128.4, 128.1, 128.1, 127.8, 127.5,
121.6, 116.8, 115.1, 114.8, 103.7, 94.7, 93.7, 77.2, 71.8, 71.7, 71.6,
70.8, 70.7, 70.4 and 68.9; m/z (ES) 729.2 (MNa+, 100%); found
729.2838; C46H42O7Na requires 729.2822.
Method 1. General Procedure for C-4 Nucleophilic Substitu-
tion of 5,7,3′,4′-Tetra-O-benzyl-4â-O-allyl-catechin (7). 5,7,3′,4′-
Tetra-O-benzyl-4â-O-allyl-catechin 7 (1 equiv) was placed in an
oven dried flask under an Argon atmosphere. Nucleophile (3 equiv)
was added followed by dry DCM (1 mL per 50 mg 7), the solution
was cooled to -78 °C. BF3‚OEt2 (1.5 equiv) was added dropwise
to the reaction, and the mixture was stirred at -78 °C for 1 h. The
reaction was quenched at -78 °C with saturated aqueous NaHCO3
solution (1 mL), and the reaction was allowed to warm to room
temperature. The mixture was diluted with CHCl3 (15 mL) and
washed with H2O (10 mL) and brine (10 mL), dried (Na2SO4), and
the solvent was evaporated under reduced pressure. The crude
product was preabsorbed onto silica and purified by column
chromatography.
with 1:10 EtOAc-petrol to yield 5,7,3′,4′-tetra-O-benzyl-4â-
(phenylsulfanyl)-catechin 16 (47 mg, 75%) as a pale red solid; Rf
0.6 (2:3 EtOAc-petrol); mp 141-143 °C; [R]26 +85.3 (c 0.86,
D
CHCl3); νmax/cm-1 (CHCl3 soln) 3574, 2927, 1615, 1591 and 1454;
1H NMR (400 MHz, CDCl3) 7.51-7.27 (21H, m), 7.19-7.10 (5H,
m), 7.06 (1H, br dd, J ) 8.4 and 2.0) 7.00 (1H, br d, J ) 8.4),
6.32 (1H, d, J ) 2.0), 6.18 (1H, d, J ) 2.0), 5.19 (4H, br s), 5.09
(1H, d, J ) 11.2), 5.04 (1H, d, J ) 11.2), 5.01 (2H, br s), 4.93
(1H, d, J ) 9.6), 4.85 (1H, d, J ) 4.4) and 4.22 (1H, dd, J ) 9.6
and 4.4); NOE irradiation at 4.22 (H3) results in enhancement at
4.85 (H4) (10.12%), irradiation at 4.85 (H4) results in enhancement
at 4.22 (H3) (6.51%); 13C NMR (100 MHz, CDCl3) 160.6, 157.9,
155.3, 149.7, 149.4, 137.5, 137.4, 136.9, 136.6, 136.5, 131.7, 131.0,
129.3, 129.1, 128.9, 128.8, 128.8, 128.7 128.3, 128.2, 128.1, 128.1,
127.9, 127.9, 127.8, 127.8, 127.8, 127.5, 127.4, 127.2, 121.7, 115.1,
114.9, 103.3, 94.4, 94.3, 78.5, 71.7, 71.5, 70.7, 70.5, 70.4 and 49.3;
m/z (ES) found 781.2588 (MNa+); C49H42O6SNa requires 781.2594.
5,7,3′,4′-Tetra-O-benzyl-4R-(1,3,5-trimethoxybenzene)-cat-
echin (17). Following Method 1, 5,7,3′,4′-tetra-O-benzyl-4â-O-
allyl-catechin 7 (50 mg, 0.07 mmol) and 1,3,5-trimethoxybenzene
(36 mg, 0.21 mmol) gave a crude product, which was purified by
column chromatography (gradient elution 20:80 f 30:70 EtOAc-
petrol) to give pure 5,7,3′,4′-tetra-O-benzyl-4R-(1,3,5-trimethoxy-
benzene)-catechin 17 (46 mg, 80%) as a colorless foam; Rf 0.1 (20:
80 EtOAc-petrol); [R]26D -76.4 (c 1.52, CHCl3); νmax/cm-1 (CHCl3
soln) 3584, 2936, 2838, 1610, 1591 and 1454; 1H NMR (400 MHz,
CDCl3) 7.49-7.25 (18H, m), 7.17 (1H, d, J ) 2.0), 7.08 (1H, dd,
J ) 8.4 and 2.0), 6.98 (1H, d, J ) 8.4), 6.94-6.92 (2H, m), 6.27
(1H, d, J ) 2.4), 6.18 (1H, d, J ) 2.4), 6.11 (1H, br s), 5.98 (1H,
br s), 5.22-5.14 (4H, m), 5.00 (2H, br s), 4.77 (1H, d, J ) 11.2),
4.65 (1H, d, J ) 8.8), 4.58 (1H, d, J ) 11.2), 4.22 (1H, dd, J )
9.6 and 8.8), 3.80 (3H, s), 3.47 (3H, s) and 3.42 (3H, s); NOE
irradiation at 4.58 (H2) results in enhancement at 4.65 (H4) (2.69%);
13C NMR (100 MHz, CDCl3) 159.7, 159.6, 159.0, 158.1, 157.9,
157.4, 149.4, 149.4, 137.6, 137.5, 137.3, 137.0, 131.9 128.8, 128.7,
128.7, 128.3, 128.2 128.2, 128.1, 128.0, 127.8, 127.8, 127.5, 127.3,
121.3, 115.3, 114.8, 113.3, 109.1, 94.9, 94.5, 92.7, 91.6, 82.5, 73.9,
71.7, 71.6, 70.3, 70.3, 56.3, 56.0, 55.5 and 37.5; m/z (ES) 839.3
(MNa+, 32%) found 839.3169; C52H48O9Na requires 839.3190.
5,7,3′,4′-Tetra-O-benzyl-4R-(1,3,5-tribenzylphloroglucinol)-
catechin (18). Following Method 1, 5,7,3′,4′-tetra-O-benzyl-4â-
O-allyl-catechin 7 (50 mg, 0.07 mmol) and 1,3,5-tribenzylphloro-
glucinol (84 mg, 0.21 mmol) gave a crude product, which was
purified by column chromatography (gradient elution 5:95 f 10:
90 EtOAc-petrol) to give pure 5,7,3′,4′-tetra-O-benzyl-4R-(1,3,5-
tribenzylphloroglucinol)-catechin 18 (50 mg, 68%) as a colorless
foam; Rf 0.3 (20:80 EtOAc-petrol); [R]26D -63.6 (c 1.50, CHCl3);
5,7,3′,4′-Tetra-O-benzyl-4â-azido-catechin (14). Following
Method 1, 5,7,3′,4′-tetra-O-benzyl-4â-O-allyl-catechin 7 (0.2 g, 0.28
mmol) and azidotrimethylsilane (112 µL, 0.84 mmol) gave a crude
product, which was purified by column chromatography (gradient
elution 5:95 f 20:80 EtOAc-petrol) to give pure 5,7,3′,4′-tetra-
O-benzyl-4â-azido-catechin 14 (0.117 g, 60%) as a colorless solid;
Rf 0.4 (20:80 EtOAc-petrol); mp 120-122 °C; [R]26 +62.1 (c
D
0.76, CHCl3); νmax/cm-1 (CHCl3 soln) 3578, 2930, 2110, 1617, 1592
and 1454; 1H NMR (400 MHz, CDCl3) 7.48-7.31 (20H, m), 7.09
(1H, br s), 7.02 (1H, br d, J ) 8.4), 7.99 (1H, br d, J ) 8.4), 6.32
(1H, d, J ) 1.6), 6.20 (1H, d, J ) 1.6), 5.19 (5H, br s), 5.12 (1H,
d, J ) 11.6), 5.06 (1H, d, J ) 11.6,), 5.01 (2H, br s), 4.85 (1H, d,
J ) 10.0), 3.99-3.96 (1H, m) and 1.99 (1H, d, J ) 6.4); NOE
irradiation at 3.97 (H3) results in enhancement at 5.19 (H4) (5.79%);
13C NMR (100 MHz, CDCl3) 161.5, 158.6, 156.1, 149.9, 149.4,
137.4, 137.3, 136.7, 136.5, 130.4, 128.9, 128.8, 128.8, 128.5, 128.4,
128.1, 128.1, 127.9, 127.8, 127.8, 127.5, 121.6, 115.1, 114.7, 101.2,
94.7, 94.1, 77.4, 71.6, 71.5, 70.7, 70.4, 70.2 and 56.0; m/z (ES)
692.2 (MH+, 20%) 649.2 (M-N3, 100%); found 692.2795;
C43H38N3O6 requires 692.2761.
5,7,3′,4′-Tetra-O-benzyl-4â-allyl-catechin (15). Following Method
1, 5,7,3′,4′-tetra-O-benzyl-4â-O-allyl-catechin 7 (0.1 g, 0.14 mmol)
and allyltributyltin (132 µL, 0.42 mmol) gave a crude product,
which was purified by column chromatography eluting with 10:90
EtOAc-petrol) to give a semi-purified product. The residue was
redissolved in MeCN (20 mL) and washed with hexane (2 × 10
mL) to remove any traces of organotin residues. Evaporation of
the MeCN layer under reduced pressure yielded pure 5,7,3′,4′-tetra-
O-benzyl-4â-allyl-catechin 15 (44 mg, 45%) as a colorless solid;
Rf 0.55 (20:80 EtOAc-petrol); mp 83-86 °C; [R]25D +12.2 (c 0.80,
CHCl3); νmax/cm-1 (CHCl3 soln) 3576, 2915, 1615, 1591 and 1454;
1H NMR (400 MHz, CDCl3) 7.49-7.31 (20H, m), 7.08 (1H, br d,
J ) 1.2), 7.00 (1H, br dd, J ) 8.4 and 1.2), 6.98 (1H, br d, J )
8.4), 6.31 (1H, d, J ) 2.4), 6.21 (1H, d, J ) 2.4), 5.99 (1H, dddd,
J ) 17.2, 10.0, 7.6 and 6.8), 5.22-5.15 (4H, m), 5.08-5.00 (5H,
m), 4.95 (1H, d, J ) 10.0), 4.94 (1H, m), 4.02 (1H, dd, J ) 10.0
and 5.6), 3.54-3.50 (1H, m), 2.74-2.67 (1H, m) and 2.54-2.48
(1H, m); NOE irradiation at 4.02 (H3) results in enhancement at
3.52 (H4) (6.24%), irradiation at 3.52 (H4) results in enhancement
of at 4.02 (H3) (5.00%); 13C NMR (100 MHz, CDCl3) 159.3, 157.9,
155.1, 149.7, 149.4, 139.2, 137.4, 137.3, 137.1, 131.7, 128.9, 128.8,
128.8, 128.7, 128.3, 128.1, 128.1, 127.9, 127.8, 127.6, 127.5, 121.4,
115.5, 115.2, 114.4, 106.9, 94.4, 93.9, 77.5, 71.9, 71.6, 71.5, 70.3,
70.3, 35.7 and 35.5; m/z (ES) 691.3 (MH+, 27%); found 691.3090;
C46H43O6 requires 691.3054.
ν
max/cm-1 (CHCl3 soln) 3586, 2872, 1608, 1591, 1454 and 1375;
1H NMR (400 MHz, CDCl3) 7.49-7.14 (34H, m), 7.05 (1H, br s),
6.99-6.92 (3H, m), 6.32 (1H, d, J ) 2.4), 6.24 (1H, d, J ) 2.4),
6.16 (1H, d, J ) 2.4), 6.11 (1H, d, J ) 2.4), 5.18 (2H, br s), 5.09
(1H, d, J ) 11.6), 5.02 (2H, br s), 5.02 (1H, d, J ) 11.6), 4.87
(1H, d, J ) 12.0), 4.86 (1H, d, J ) 8.8), 4.80-4.71 (2H, m), 4.75
(1H, d, J ) 12.0), 4.62 (1H, d, J ) 11.2), 4.61 (1H, d, J ) 9.6),
4.52 (1H, d, J ) 12.0) and 4.37 (1H, dd, J ) 9.6 and 8.8); 13C
NMR (100 MHz, CDCl3) 158.9, 158.5, 158.1, 157.8, 157.5, 157.2,
157.0, 149.2, 149.1, 137.5, 137.4, 137.2, 137.1, 137.1, 137.0, 136.8,
132.0, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.2, 128.2, 128.1,
128.0, 127.8, 127.8, 127.7, 127.6, 127.5, 127.4, 127.3, 127.2, 121.1,
115.0, 113.9, 113.1, 108.7, 94.9, 94.3, 93.9, 93.7, 82.1, 73.0, 71.4,
71.2, 71.0, 70.6, 70.2, 70.2, 70.0, 69.7 and 37.5; m/z (ES) found
1067.4129 (MNa+); C70H60O9Na requires 1067.4129.
5,7,3′,4′-Tetra-O-benzyl-4-(5,7,3′,4′-tetra-O-benzylcatechin)-
catechin (19). Following Method 1, 5,7,3′,4′-tetra-O-benzyl-4â-
O-allyl-catechin 7 (100 mg, 0.14 mmol) and 5,7,3′,4′-tetra-O-
benzylcatechin (276 mg, 0.42 mmol) gave a crude product, which
was purified by column chromatography (gradient elution 20:80
f 25:75 EtOAc-petrol) to give pure 5,7,3′,4′-tetra-O-benzyl-4-
(5,7,3′,4′-tetra-O-benzylcatechin)-catechin 19 (95 mg, 52%, 3.5:1
5,7,3′,4′-Tetra-O-benzyl-4â-(phenylsulfanyl)-catechin (16). Fol-
lowing Method 1, 5,7,3′,4′-tetra-O-benzyl-4â-O-allyl-catechin 7 (58
mg, 0.08 mmol) and thiophenol (25 µL, 0.24 mmol) gave a crude
product, which was purified by column chromatography eluting
J. Org. Chem, Vol. 71, No. 26, 2006 9707