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Vol. 51, No. 11
gle arylaldehyde, produced symmetrical diglycoside and (12H, OAc). 13C-NMR: 190.9 (CHO), 170.3, 170.1, 170.1, 169.3 (CϭO),
151.7, 150.9, 132.7 (s, aromatic), 125.4, 117.9, 110.6 (d, aromatic), 100.3
(d), 71.2, 70.5, 68.4, 66.7 (d), 61.3 (t), 56.1 (OMe), 20.6, 20.6, 20.6, 20.5
(OCOMe).
method B, which uses a mixture of glycosylated arylalde-
hyde and non-protected arylaldehyde, were appropriate to
yield unsymmetrical mono-glycoside. Removal of the boron
Acetylacetone–B2O3 Complex Boric oxide (B2O3) was dried under re-
group from the product was achieved by refluxing with
MeOH. Deacetylation from the sugar moiety was achieved in
good yield by treatment with methanolic ammonia.
duced pressure at 250 °C for 3 h. The dried oxide (0.13 g, 1.8 mmol) was
added to acetylacetone (0.25 g, 2.5 mmol) and the mixture was stirred at
room temperature for 30 min, and then used directly.
Synthesis of Curcuminoid Glycosides. Method A (Typical Example)
To a stirred solution of 8 (2.4 g, 5 mmol) in dry AcOEt (30 ml) was added
tri-(n-butyl) borate (BuO)3B (2.5 ml), and the mixture was stirred for 10 min
Experimental
Unless otherwise stated, the following procedure was adopted. Melting at room temperature. The above-prepared acetylacetone–B2O3 complex was
points were determined on a Yanaco melting point apparatus and are uncor- then added to this solution. After stirring for 10 min at room temperature, n-
rected. IR spectra were recorded on a JASCO IR-810 spectrophotometer, butylamine (0.05 ml) was added to the solution, and the reaction mixture
and data are given in cmϪ1. UV spectra were recorded on a Hitachi U-2000 was stirred at room temperature for 20 h. The mixture was concentrated to
spectrophotometer and the absorption wavelengths are expressed in nm fol- dryness in vacuo. MeOH (200 ml) was added to the residue and the solution
lowed by (e). 1H- and 13C-NMR spectra were taken with a JEOL JNM-EX90 was heated under reflux for 4 h, following which the solvent was evaporated
(90 MHz for 1H and 22.5 MHz for 13C) or JEOL JNM-AL300 (300 MHz for
under reduced pressure. The residue was purified by silica gel column chro-
1H and 75 MHz for 13C) spectrometer, in CDCl3 solutions with tetramethylsi- matography (AcOEt : hexaneϭ3 : 2) to give 11 (1.4 g, 51%). The following
lane as an internal standard and the chemical shifts are given in d values. compounds were prepared in this way.
High resolution (HR)-FAB-MS were recorded using a JEOL MStation JMS-
700 spectrometer, with 3-nitrobenzylalcohol as the matrix. Elemental analy- 172—174 °C. IR (KBr): 3450, 1760, 1630. UV (MeOH): 260 (16800), 408
ses of C and H were carried out on a Thermo Quest FlashEA 1112 microan-
(47000). 1H-NMR: 7.59 (2H, d, Jϭ15.6 Hz, H-1, 7), 7.27—7.10 (6H, m, Ar-
Diglucosylcurcumin Octaacetate 11: Yellow amorphous powder, mp
alyzer. TLC was performed on pre-coated Kieselgel 60 F254 plates and spots H), 6.56 (2H, d, Jϭ15.6 Hz, H-2, 6), 5.84 (1H, s, H-4), 5.26—5.06 (10H, m,
were monitored by UV (254 nm), then developed by spraying 0.5% Glc-H), 4.32—4.15 (4H, m, Glc-H), 3.87 (6H, s, OMe), 2.08—2.04 (24H,
Ce(SO4)2–0.5% (NH4)6Mo7O24 in 5% H2SO4 and heating the plates until col- m, OAc). HR-FAB-MS (positive-ion mode) m/z: 1029.3242 [MϩH]ϩ (Calcd
oration took place. Column chromatography was performed on Wakogel C- for C49H57O24: 1029.3240). Anal. Calcd for C49H56O24·1/2H2O: C, 56.70; H,
200 (silica gel). For medium-pressure liquid chromatography (MPLC), a Ku- 5.54. Found: C, 56.97; H, 5.51.
sano CPS-HS-221-1 column (silica gel, 22 mm i.d.ϫ100 mm) was used.
Identification of curcumin 1 and bis-demethoxycurcumin 3 was performed 5 mmol) was treated as described in method A with (BuO)3O (2.5 ml), ace-
by mp and TLC comparisons with the authentic specimen,8) respectively.
tylacetone–B2O3 complex which was prepared from acetylacetone (0.25 g,
Tetra-O-acetyl-a-D-glucopyranosyl Bromide To a mixture of penta-O- 2.5 mmol) and boric oxide (0.13 g, 1.8 mmol), and n-butylamine (0.05 ml) to
acetyl-b-D-glucopyranose (23.4 g, 60 mmol) and red phosphorous (3.6 g,
give 13 (1.2 g, 51%), as pale yellow amorphous powder, mp 185—188 °C.
Diglucosyl-bis-demethoxycurcumin Octaacetate 13: Compound 9 (2.26 g,
1
116 mmol) in CHCl3 (100 ml) was added Br2 (21.6 g, 135 mmol) carefully in IR (KBr): 1760, 1740. UV (CHCl3 : MeOHϭ10 : 1): 407 (43700). H-NMR
a dropwise manner and the resulting mixture was stirred for 30 min. Then (CDCl3ϩCD3OD): 7.61 (2H, d, Jϭ15.6 Hz, H-1, 7), 7.52, 7.01 (each 4H, d,
water (4 ml) was added dropwise, and the mixture was stirred at room tem- Jϭ8.7 Hz, Ar-H), 6.53 (2H, d, Jϭ15.6 Hz, H-2, 6), 5.82 (1H, s, H-4), 5.35—
perature for 2 h. After filtration of insoluble materials, the organic layer was 3.87 (14H, m, Glc-H), 2.30—2.06 (24H, m, OAc). HR-FAB-MS (positive-
washed with water and stirred vigorously with saturated aqueous NaHCO3
solution for 10 min. The organic layer was separated, washed with water, Calcd for C47H52O22·1/2H2O: C, 57.73; H, 5.46. Found: C, 57.73; H, 5.55.
dried over anhydrous Na2SO4, and concentrated. A solid residue was recrys-
Digalactosylcurcumin Octaacetate 15: Compound 10 (2.4 g, 5 mmol)
ion mode) m/z: 969.3053 [MϩH]ϩ (Calcd for C47H53O22: 969.3028). Anal.
tallized from hexane–Et2O to afford acetobromoglucose as colorless needles was treated as described in method A with (BuO)3O (2.5 ml), acetylace-
(20.83 g, 84%). mp 86—88 °C (lit. mp 88—89 °C12)).
tone–B2O3 complex which was prepared from acetylacetone (0.25 g,
Tetra-O-acetyl-a-D-galactopyranosyl Bromide Penta-O-acetyl-b-D-
2.5 mmol) and boric oxide (0.13 g, 1.8 mmol), and n-butylamine (0.05 ml) to
galactose gave acetobromogalactose in 90% yield as a colorless gum. This give 15 (1.54 g, 56%), as yellow amorphous powder, mp 102—105 °C. IR
was used for the next reaction without further purification.
(KBr): 1770, 1740. UV (MeOH): 260 (11900), 407 (39700). 1H-NMR: 7.60
Glycosylation of Hydroxyarylaldehyde (Typical Example) 1 N NaOH
(2H, d, Jϭ15.8 Hz, H-1, 7), 7.12—7.08 (6H, m, Ar-H), 6.53 (2H, d,
aq (150 ml) was added at room temperature to a stirred solution of vanillin 6 Jϭ15.8 Hz, H-2, 6), 5.85 (1H, s, H-4), 5.56—5.45 (4H, m, Gal-H), 5.14—
(13.6 g, 89.2 mmol), acetobromoglucose (18.3 g, 44.6 mmol) and Bu4NBr 4.96 (4H, m, Gal-H), 4.25—4.02 (6H, m, Gal-H), 3.88 (6H, s, OMe), 2.18—
(14.6 g, 44.6 mmol) in CHCl3 (150 ml). The resulting mixture was stirred 2.02 (24H, m, OAc). HR-FAB-MS (positive-ion mode) m/z: 1029.3235
vigorously at room temperature for 1 h. After dilution with AcOEt, the or- [MϩH]ϩ (Calcd for C49H57O24: 1029.3240).
ganic layer was washed with 1 N NaOH aq, water and brine, dried over anhy-
Method B (Typical Example) To a stirred solution of 8 (2.4 g, 5 mmol)
drous Na2SO4, and concentrated in vacuo. The crude product was recrystal- and vanillin 6 (0.765 g, 5 mmol) in dry AcOEt (30 ml) was added (BuO)3B
lized from EtOH to give 8 (10.8 g, 50%) as colorless needles. The following (5 ml) at room temperature, and the mixture was stirred for 10 min. Then
compounds were prepared in this way.
Tetra-O-acetyl-b-D-glucopyranosylvanillin 8: mp 135—137 °C (lit. mp
acetylacetone–B2O3 complex, prepared from B2O3 (0.25 g, 3.6 mmol) and
acetylacetone (0.5 g, 5 mmol), was added to the solution. After stirring for
142 °C16)). 1H-NMR: 9.90 (1H, s, CHO), 7.47—7.16 (3H, m, Ar-H), 5.35— 10 min at room temperature, n-butylamine (0.1 ml) was added, and the reac-
5.06 (4H, m, Glc-H), 4.28—4.22 (2H, m, Glc-H), 3.90 (3H, s, OMe), 3.88— tion mixture was stirred at room temperature for a further 20 h. The resulting
3.85 (1H, m, Glc-H), 2.07—2.05 (12H, OAc). 13C-NMR: 190.9 (CHO), mixture was concentrated in vacuo, and the residue was heated under reflux
170.5, 170.2, 169.4, 169.2 (CϭO), 151.0, 150.9, 132.8 (s, aromatic), 125.3, with MeOH (200 ml) for 4 h. Evaporation of the solvent and purification of
118.1, 110.7 (d, aromatic), 99.7 (d), 72.3, 72.2, 70.9, 68.2 (d), 61.8 (t), 56.1 the residue by MPLC (AcOEt : hexaneϭ3 : 2) gave curcumin 1 (281 mg,
(OMe), 20.7, 20.6, 20.6ϫ2 (OCOMe).
15%), monoglucoside 12 (1.2 g, 34%), and diglucoside 11 (204 mg, 4%).
The following compounds were synthesized in this way.
Monoglucosylcurcumin Tetraacetate 12: Yellow amorphous powder, mp
Tetra-O-acetyl-b-D-glucopyranosyl-4-hydroxybenzaldehyde 9: This was
obtained from 4-hydroxybenzaldehyde in 54% yield as colorless needles, mp
142—143 °C (lit. mp 145—147 °C17)). H-NMR: 9.93 (1H, s, CHO), 7.86 86—88 °C. IR (KBr): 3420, 1750. UV (MeOH): 259 (11700), 416 (41400).
1
(2H, d, Jϭ8.6 Hz, Ar-H), 7.11 (2H, d, Jϭ8.6 Hz, Ar-H), 5.34—5.16 (4H, m,
1H-NMR: 7.61, 7.56 (each 1H, d, Jϭ15.8 Hz, H-7, H-1), 7.12—6.91 (6H, m,
Glc-H), 4.33—4.16 (2H, m, Glc-H), 3.97—3.92 (1H, m, Glc-H), 2.08—2.05 Ar-H), 6.52, 6.47 (each 1H, d, Jϭ15.8 Hz, H-6, H-2), 5.81 (1H, s, H-4),
(12H, OAc). 13C-NMR: 190.7 (CHO), 170.4, 170.1, 169.3, 169.2 (CϭO), 5.31—3.80 (7H, m, Glc-H), 3.94, 3.86 (each 3H, s, OMe), 2.09—2.05 (12H,
161.2, 131.8 (s, aromatic), 131.8ϫ2, 116.7ϫ2 (d, aromatic), 98.0 (d), 72.5, m, OAc). HR-FAB-MS (positive-ion mode) m/z: 699.2311 [MϩH]ϩ (Calcd
72.2, 70.9, 68.0 (d), 61.8 (t), 20.6, 20.5, 20.5ϫ2 (OCOMe).
for C35H39O15: 699.2289).
Tetra-O-acetyl-b-D-galactopyranosylvanillin 10: This was obtained by the
Monoglucosyl-bis-demethoxycurcumin Tetraacetate 14: Compound 9
reaction of acetobromogalactose and vanillin in 85% yield, as colorless nee- (2.26 g, 5 mmol) and 4-hydroxybenzaldehyde 7 (614 mg, 5 mmol) were
dles, mp 124—125 °C (lit. mp 123—124 °C18)). 1H-NMR: 9.90 (1H, s, treated as described in method B with (BuO)3O (2.5 ml), acetylacetone–
CHO), 7.43—7.22 (3H, m, Ar-H), 5.59—5.46 (2H, m, Gal-H), 5.15—5.05 B2O3 complex which was prepared from acetylacetone (0.25 g, 2.5 mmol)
(2H, m, Gal-H), 4.28—4.14 (3H, m, Gal-H), 3.90 (3H, s, OMe), 2.18—2.03 and boric oxide (0.13 g, 1.8 mmol), and n-butylamine (0.05 ml) to give 3