Journal of Natural Medicines
was extracted with EtOAc. The EtOAc extract was washed
with aq. satd. NaCl, then dried over MgSO4. Removal of
the solvent from the EtOAc extract under reduced pres-
sure gave a residue, which was purifed by column chroma-
tography (SiO2 15 g, n-hexane:EtOAc = 2:3) to aford 17
(335 mg, 97%). 2,3-O-Bis-tribenylgalloyl-1-O-methyl glu-
cose 17; a colorless amorphous powder, 1H-NMR (CDCl3)
δ: 3.38 (2.52H, s, β-isomer), 3.45 (0.48H, s, α-isomer),
3.78–3.98(4H, m), 4.55 (0.16H, d, J = 7.9 Hz, α-isomer),
4.86–5.00 (12H, m), 5.06–5.08 (1.68H, m, β-isomer), 5.20
(0.16H, dd, J = 9.2, 9.2 Hz, α-isomer), 5.32 (0.16H, dd,
J=7.9, 9.2 Hz, α-isomer), 5.58 (0.84H, dd, J=9.2, 9.2 Hz,
β-isomer), 7.13–7.35 (34H, m). IR (KBr): 2922, 1734 cm−1;
FAB-MS m/z: 1041 (M+H)+. HRFAB-MS m/z: 1041.3987
(Calcd for C63H61O14+: 1041.3983). [β]2D4 +40.8° (c 0.72,
MeOH).
Preparation of protected HHDP 13
Carbomethoxy carboxylic acid 12 (1.6 g, 1.8 mmol) was
treated with methanolic KOH (3 M, 9.0 mL, 27 mmol)
at 40 °C for 3 h. After cooling to room temperature, aq.
satd. KHSO4 was added to the reaction mixture, then the
whole was extracted with CH2Cl2. The CH2Cl2 extract
was dried over MgSO4. Removal of the solvent from the
CH2Cl2 extract under reduced pressure gave a residue,
which was purifed by column chromatography (SiO2 50 g,
CHCl3:MeOH: H2O=30:3:1 [lower layer]) to aford lactone
13 (990 mg, 65%).
Protected HHDP 13; a colorless amorphous pow-
1
der, H-NMR (CDCl3) δ: 5.08 (4H, s), 6.91–7.09 (12H,
m), 7.45–7.66 (20H, m). IR (KBr): 3063, 3032, 1698,
1611 cm−1. FAB-MS m/z: 869 (M+Na)+. HRFAB-MS m/z:
869.2469 (Calcd for C54H38O10Na+: 869.2465). [β]D24 −36.6°
(c 0.50, MeOH).
Preparation
of 2,3‑O‑bis‑tribenylgalloyl‑4,6‑O‑protected
HHDP‑1‑O‑methyl glucose 18
Preparation of 4,6‑O‑acetonide‑1‑O‑methyl glucose
15
A solution of 17 (335 mg, 0.31 mmol) and protected HHDP
(263 mg, 0.31 mmol) in CH2Cl2 (3.1 mL) was treated with
2-methyl-6-nitrobenzoic anhydride (MNBA, 640 mg,
1.9 mmol) in the presence of triethylamine (0.43 mL,
3.1 mmol) and DMAP (113 mg, 0.93 mmol) at room tem-
perature for 3 h. To the reaction mixture, aq. satd. NaCl was
added, then the whole was extracted with EtOAc. The EtOAc
extract was washed with 5% HCl, aq. satd. NaHCO3 and aq.
satd. NaCl sequentially, then dried over MgSO4. Removal
of the solvent from the EtOAc extract under reduced pres-
sure gave a residue, which was purifed by column chroma-
tography (SiO2 15 g, benzene:n-hexane:EtOAc=10:10:1)
to aford 18a (β-isomer, 349 mg, 61%) and 18b (α-isomer,
69 mg, 12%).
A solution of 1-O-methyl glucose 14 (96 mg, 0.49 mmol)
in DMF (1.0 mL) was treated with 2,2-dimethoxypropane
(0.48 mL, 3.9 mmol) and p-toluenesulfonic acid (4.2 mg,
0.025 mmol) at room temperature for 1 h. To the reaction
mixture, aq. satd. NaHCO3 was added, then the whole was
extracted with CH2Cl2. The CH2Cl2 extract was dried over
MgSO4. Removal of the solvent from the CH2Cl2 extract
under reduced pressure gave a residue, which was purifed
by column chromatography (SiO2 50 g, CHCl3:MeOH:
H2O=50:3:1 [lower layer]) to aford 15 (75 mg, 65%). The
structure of 15 was identifed by comparison of spectro-
scopic data with reported one [26].
18a; a colorless amorphous powder, 1H-NMR (CDCl3) δ:
3.42 (3H, s), 3.94 (1H, d, J=12.8 Hz), 4.43 (1H, dd, J=7.9,
9.7 Hz), 4.67–5.09 (17H, m), 5.23 (1H, d, J = 3.7 Hz),
5.28–5.34 (2H, m), 5.91 (1H, dd, J = 9.8, 10.4 Hz), 6.69
(1H, s), 6.73 (1H, s), 6.82–7.59 (64H, m). IR (KBr): 3090,
3034, 1747 cm−1. FAB-MS m/z: 1849 (M+H)+. HRFAB-
MS m/z: 1849.6080 (Calcd for C117H93O22+: 1849.6114).
[β]2D4 +12.5° (c 0.78, MeOH).
Preparation of 2,3‑O‑bis‑tribenylgalloyl‑1‑O‑methyl
glucose 17
A solution of 15 (75 mg, 0.32 mmol) in CH2Cl2 (3.2 mL)
was treated with tri-O-benzylgallic acid (16, 352 mg,
0.8 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodi-
imide hydrochloride salt (EDCI·HCl, 368 mg, 1.9 mmol) in
the presence of 4-dimethylaminopyridine (DMAP, 19 mg,
0.16 mmol) at room temperature overnight. To the reac-
tion mixture, aq. satd. NaCl was added, then the whole was
extracted with EtOAc. The EtOAc extract was washed with
5% HCl, aq. satd. NaHCO3 and aq. satd. NaCl sequentially,
then dried over MgSO4. Removal of the solvent from the
EtOAc extract under reduced pressure gave a crude bis-
tribenylgalloyl product (488 mg). A solution of the crude
product (488 mg) in MeOH (6.4 mL) was treated with I2
(81.2 mg, 0.32 mmol) under refux for 1 h. To the reac-
tion mixture, aq. satd. Na2S2O3 was added, then the whole
18b; a colorless amorphous powder, 1H-NMR (CDCl3) δ:
3.53 (3H, s), 4.03 (1H, d, J=12.8 Hz), 4.35 (1H, dd, J=6.1,
10.4 Hz), 4.61 (1H, d, J=7.3 Hz), 4.91–5.12 (16H, m), 5.31
(1H, dd, J=9.8, 10.4 Hz), 5.38 (1H, dd, J=6.1, 12.8 Hz),
5.44 (1H, dd, J=7.3, 9.8 Hz), 5.59 (1H, dd, J=9.8, 9.8 Hz),
6.74 (1H, s), 6.81 (1H, s), 6.82–7.59 (64H, m). IR (KBr):
3063, 2932, 1732 cm−1. FAB-MS m/z: 1849 (M + H)+.
+
HRFAB-MS m/z: 1849.6110 (Calcd for C117H93O22
:
1849.6114). [β]D24 +11.6° (c 0.88, MeOH).
1 3