Synthesis of Unusual Ellagitannins
J . Org. Chem., Vol. 63, No. 24, 1998 8727
1-O-(o-Nitr oben zyl)-2,3-O-[(R)-2,2′,3,3′,4,4′-h exa ben zyl-
oxyd ip h en oyl]-â-D-glu cop yr a n osid e (9). A solution of ben-
zylidene acetal 8 (3.08 g, 2.47 mmol) in THF (65 mL), was
treated dropwise at 60 °C with 2 N HCl (65 mL) and the
reaction mixture was refluxed at 78 °C for 6 h. After cooling
to room temperature, the reaction mixture was carefully
neutralized with a saturated NaHCO3 solution and extracted
five times with EtOAc (80 mL). The combined organic phases
were dried (Na2SO4) and filtered, and the solvent was removed
in vacuo to give an orange residue. Column chromatography
on silica gel (CH2Cl2/EtOAc, 80:20) gave the diol 9 (2.65 g, 86%,
74 (t), 75.87 (t), 79.67 (2 × d), 90.95 (d), 109.64 (d), 109.93 (d),
110.10 (d), 110.17 (d), 124.79 (s), 124.92 (s), 125.03 (s), 125.11
(s), 126.60 (s), 128.06 (d), 128.26 (d), 128.29 (d), 128.55 (d),
128.63 (d), 128.78 (d), 128.81 (d), 128.91 (d), 128.98 (d), 129.12
(d), 129.33 (d), 136.67 (s), 136.83 (s), 136.91 (s), 137.02 (s),
137.13 (s), 137.19 (s), 137.95 (s), 138.01 (s), 138.08 (s), 143.17
(s), 143.75 (s), 143.86 (s), 152.56 (s), 152.68 (s), 153.11 (s),
153.34 (s), 153.62 (s), 153.72 (s), 165.35 (s), 165.52 (s), 166.43
(s), 167.78 (s); MS (FAB/NBA) m/z (rel intensity) 1867 (M+
+
1, 9), 1775 (M+ - C7H7, 100). Anal. Calcd for C118H98O22: C,
75.87; H, 5.29. Found: C, 75.88; H, 5.29.
20
mp 72-73 °C) as a faintly yellow powder: [R]D +46° (c 0.05,
2,3-O-[(R)-2,2′,3,3′,4,4′-Hexa h yd r oxyd ip h en oyl]-4,6-d i-
O-ga lloyl-D-glu cosid e (P a r iin M) (2). A suspension of
benzylprotected compound 11 (0.40 g, 0.21 mmol), Pd/C (0.20
g, 10%), and dry THF (25 mL) was degassed with argon (3
times) to remove O2, and H2 was conducted slowly through
the reaction mixture for 24 h at room temperature. The
reaction mixture was filtered through Celite, and the Celite
was washed with a mixture of acetone/MeOH (70:30, 100 mL).
The solvent was removed in vacuo to give an oil. Reversed
phase chromatography (H2O/MeOH, 80:30) gave debenzylated
product 2 (0.14 g, 83%, dec > 230 °C, powder) as an anomeric
CH2Cl2); IR (KBr, cm-1) ν 1718 (CO, ester); UV/vis (λmax (lg ꢀ))
1
270 nm (4.41); H NMR (CDCl3, 300 MHz) δ 3.32-3.46 (m, 2
H), 3.76 (dd, J ) 4.2 Hz, J ) 12.0 Hz, 1 H), 3.86 (dd, J ) 3.0
Hz, J ) 12.0 Hz, 1 H), 4.38-5.16 (m, 16 H), 5.24 (d, J ) 14.6
Hz, 1 H), 6.64 (s, 1 H), 6.67 (s, 1 H), 6.80-7.39 (m, 31 H), 7.49
(t, J ) 7.5 Hz, J ) 7.6 Hz, 1 H), 7.71 (d, J ) 7.6 Hz, 1 H), 7.95
(dd, J ) 8.1 Hz, J ) 1.0 Hz, 1 H); 13C NMR (CDCl3, 75 MHz)
δ 62.08 (t), 68.42 (d), 68.69 (t), 71.41 (t), 71.59 (t), 75.45 (t),
75.63 (t), 75.69 (t), 75.87 (t), 76.45 (2 × d), 82.55 (d), 99.98 (d),
111.05 (d), 124.63 (s), 125.35 (d), 127.53 (d), 127.61 (d), 127.89
(d), 127.93 (d), 127.97 (d), 128.10 (d), 128.17 (d), 128.21 (d),
128.25 (d), 128.36 (d), 128.47 (d), 128.57 (d), 129.00 (d), 133.27
(s), 133.52 (d), 136.12 (s), 136.22 (s), 136.98 (s), 137.23 (s),
137.25 (s), 137.36 (s), 147.34 (s), 151.93 (s), 152.27 (s), 152.64
(s), 168.40 (s), 169.03 (s); MS (FAB/NBA) m/z (rel intensity)
1158 (M+ + 1, 37), 1157 (M+, 48), 1066 (M+ - C7H7, 94), 1021
(M+ - C7H6NO2, 100). Anal. Calcd for C69H59O16N: C, 71.55;
H, 5.13; N, 1.21. Found: C, 71.37; H, 5.10; N, 1.15.
20
20
mixture (R:â, 70:30): [R]D -5° (c 0.2, MeOH), [R]D -6° (c
0.13, MeOH); IR (KBr, cm-1) ν 1718 (CO, ester); UV/vis (λmax
(lg ꢀ)) 281 nm (4.38); H NMR (acetone-d6/D2O, 200 MHz) δ
1
3.99-4.20 (m, 3 H), 4.41-4.67 (m, 4 H), 4.74 (dd, J ) 3.4 Hz,
J ) 9.7 Hz, 1 H), 5.00 (d, J ) 7.8 Hz, 1 H), 5.16-5.25 (m, 2
H), 5.29-5.37 (m, 2 H), 5.44 (d, J ) 3.4 Hz, 1 H), 6.73 (br. s,
2 H), 6.90 (br. s, 2 H), 7.03 (s, 2 H), 7.05 (s, 2 H), 7.09 (s, 2 H),
7.12 (s, 2 H); 13C NMR (acetone-d6/D2O, 50 MHz) δ 62.87 (2 ×
t), 67.92 (d), 68.60 (d), 68.86 (d), 73.39 (d), 76.28 (2 × d), 78.29
(d), 78.67 (d), 90.45 (d), 94.35 (d), 108.08 (d), 109.68 (d), 109.92
(d), 116.79 (s), 117.39 (s), 117.49 (s), 119.57 (s), 120.31 (s),
120.85 (s), 136.94 (s), 137.32 (s), 138.30 (s), 138.85 (s), 139.30
(s), 139.35 (s), 144.24 (s), 144.34 (s), 144.46 (s), 144.85 (s),
144.96 (s), 145.42 (s), 145.49 (s), 145.53 (s), 165.82 (s), 166.99
(s), 168.81 (s), 169.07 (s), 169.44 (s), 169.70 (s) {the signals of
the quarternary HHDP-C-6R/6â and HHDP-C-6′R/6′â at ca.
125 ppm could not unambiguously be assigned, because of their
low-intensities}; MS (FAB/NBA) m/z (rel intensity) 786 (M+,
5), 153 (100). Anal. Calcd for C34H26O22‚3H2O: C, 48.58; H,
3.84. Found: C, 48.44; H, 4.05.
1-O-(o-Nitr oben zyl)-2,3-O-[(R)-h exa ben zyloxyd ip h en -
oyl]-4,6-d i-O-(3,4,5-tr i-O-ben zylga lloyl)-â-D-glu cop yr a n o-
sid e (10). A mixture of diol 9 (1.63 g, 1.41 mmol), 3,4,5-tri-
O-benzylgallic acid (1.49 g, 3.38 mmol), DCC (0.70 g, 3.38
mmol) and DMAP (0.41 g, 3.38 mmol) in dry CH2Cl2 (100 mL)
was refluxed under argon for 24 h. After cooling to room
temperature, the white precipitate (dicyclohexylurea) was
filtered off. The organic phase was washed twice with water
(60 mL) and dried (Na2SO4), and the solvent was removed in
vacuo to give an oil. The product was chromatographed on
silica gel (CH2Cl2/Et2O, 99:1) to yield 10 (2.00 g, 71%, mp 76-
20
77 °C) as a faintly yellow powder: [R]D -14° (c 0.1, CH2Cl2);
IR (KBr, cm-1) ν 1723 (CO, ester); UV/vis (λmax (lg ꢀ)) 270 nm
(4.64); 1H NMR (CDCl3, 200 MHz) δ 4.05-4.11 (m, 1 H, H-5),
4.39 (dd, J ) 6.0 Hz, J ) 12.1 Hz, 1 H), 4.54 (d, J ) 10.7 Hz,
1 H), 4.62 (d, J ) 11.2 Hz, 1 H), 4.69 (dd, J ) 3.4 Hz, J ) 12.1
Hz, 1 H), 4.85-5.24 (m, 27 H), 5.35 (d, J ) 14.8 Hz, 1 H,),
6.81-7.47 (m, 67 H), 7.56 (t, J ) 7.1 Hz, J ) 7.8 Hz, 1 H),
7.81 (d, J ) 7.8 Hz, 1 H), 8.04 (d, J ) 8.1 Hz, 1 H); 13C NMR
(CDCl3, 50 MHz) δ 64.12 (t), 69.05 (t), 70.40 (d), 71.47 (t), 71.63
(t), 71.76 (t), 72.81 (d), 75.70 (t), 75.80 (t), 75.91 (t), 76.16 (t),
78.48 (2 × d), 100.36 (d), 109.62 (d), 110.06 (d), 124.64 (s),
125.04 (s), 125.44 (d), 125.90 (s), 126.43 (s), 128.20 (d), 128.28
(d), 128.46 (d), 128.59 (d), 128.75 (d), 128.89 (d), 129.09 (d),
129.12 (d), 129.30 (d), 129.52 (d), 133.76 (s), 134.19 (d), 136.70
(s), 137.06 (s), 137.19 (s), 137.29 (s), 137.93 (s), 138.03 (s),
138.09 (s), 138.15 (s), 143.27 (s), 143.69 (s), 148.05 (s), 152.74
(s), 152.80 (s), 153.14 (s), 153.25 (s), 165.52 (s), 166.19 (s),
167.35 (s), 168.37 (s); MS (FAB/NBA) m/z (rel intensity) 2002
(M+ + 1, 8), 2001 (M+, 15), 1850 (100). Anal. Calcd for
1,4,6-T r i-O -(3,4,5-t r i-O -b e n zy lg a llo y l)-2,3-O -[(R )-
2,2′,3,3′,4,4′-h exa ben zyloxyd ip h en oyl]-â-D-glu cop yr a n o-
sid e (12). A solution of 11 (0.60 g, 0.32 mmol), 3,4,5-tri-O-
benzylgalloyl chloride (0.22 g, 0.48 mmol), dry triethylamine
(3 drops), and dry CH2Cl2 (15 mL) was refluxed for 4 h. The
reaction mixture was allowed to cool to room temperature, and
the solvent was removed in vacuo. The residue was separated
by column chromatography (CH2Cl2) to give the anomeric
acylated compound 12 (0.51 g, 69%, mp 78-79 °C) as a faintly
yellow powder: [R]D -13.5° (c 0.2, CH2Cl2); IR (KBr, cm-1) ν
20
1725 (CO, ester); UV/vis (λmax (lg ꢀ)) 273 nm (4.86); 1H (CDCl3,
300 MHz) δ 4.29-4.32 (m, 1 H), 4.39 (dd, J ) 6.4 Hz, J ) 11.8
Hz, 1 H), 4.60 (d, J ) 10.8 Hz, 1 H), 4.76-4.82 (m, 1 H), 4.90-
5.46 (m, 33 H), 6.84-7.59 (m, 83 H); 13C NMR (CDCl3, 50 MHz)
δ 63.79 (t), 69.78 (d), 71.56 (t), 71.83 (t), 72.09 (t), 73.58 (d),
75.68 (t), 75.74 (t), 75.83 (t), 78.82 (d), 78.95 (d), 92.47 (d),
109.58 (d), 110.45 (d), 124.13 (s), 124.41 (s), 125.05 (s), 126.60
(s), 126.69 (s), 128.08 (d), 128.24 (d), 128.35 (d), 128.40 (d),
128.55 (d), 128.59 (d), 128.72 (d), 128.79 (d), 128.90 (d), 128.96
(d), 129.12 (d), 129.27 (d), 136.52 (s), 136.56 (s), 136.94 (s),
137.02 (s), 137.24 (s), 137.69 (s), 137.84 (s), 137.90 (s), 138.07
(s), 143.17 (s), 143.97 (s), 144.23 (s), 147.05 (s), 152.26 (s),
152.56 (s), 153.10 (s), 153.28 (s), 153.33 (s), 153,40 (s), 164.66
(s), 165.16 (s), 166.20 (s), 166.65 (s), 167.97 (s); MS (FAB/NBA)
m/z (rel intensity) 2195 (M+ + 1 - C6H6O, 6). Anal. Calcd
for C146H120O26: C, 76.56; H, 5.28. Found: C, 76.62; H, 5.19.
1,4,6-Tr i-O-ga lloyl-2,3-O-[(R)-2,2′,3,3′,4,4′-h exa h yd r oxy-
C
125H103NO24: C, 74.95; H, 5.18; N, 0.70. Found: C, 74.88;
H, 5.13; N, 0.80.
2,3-O-[(R)-2,2′,3,3′,4,4′-H exa b en zyloxyd ip h en oyl]-4,6-
d i-O-(3,4,5-tr i-O-ben zylga lloyl)-D-glu cosid e (11). A solu-
tion of compound 10 (1.45 g, 0.72 mmol) in THF (120 mL),
EtOH (120 mL), and H2O (1 mL) was irradiated at 320 nm in
a PYREX apparatus for 6 h. The solvent was removed in vacuo
to give an oil. The product was chromatographed on silica gel
(CH2Cl2/Et2O, 97:3) to yield glucoside 11 (1.19 g, 88%, mp 158-
159 °C, yellow powder) as an R,â-anomeric mixture (R:â, ca.
80:20): [R]D20 +10° (c 0.1, CH2Cl2); IR (KBr, cm-1) ν 1724 (CO,
ester); UV/vis (λmax (lg ꢀ)) 270 nm (4.91). Data for the R-anomer
(R-11): 1H NMR (CDCl3, 200 MHz) δ 4.24-5.34 (m, 31 H),
6.83-7.46 (m, 66 H); 13C NMR (CDCl3, 50 MHz) δ 63.40 (t),
68.08 (d), 71.11 (d), 71.59 (t), 71.74 (t), 71.84 (t), 71.96 (t), 75,
d ip h en oyl]-â-D-glu cop yr a n osid e (Ma h ta bin A) (1).
A
suspension of benzylated substance 12 (0.40 g, 0.17 mmol),
Pd/C (0.20 g, 10%) in dry THF (25 mL) was treated with
hydrogen, according to the procedure for 2, to give after
reversed phase chromatography (H2O/MeOH, 80:40) the depro-
tected compound 1 (0.14 g, 85%, dec > 225 °C) as a powder: