9270 J . Org. Chem., Vol. 64, No. 25, 1999
Notes
EtOAc, washing with brine, drying over Na2SO4, and evapora-
tion in vacuo.
CO3 solution, and worked up to give a colorless solid. Recrys-
tallization of the solid from EtOH gave 8 (4.7 g, 92%) as colorless
crystals: mp 143-144 °C; [R]20D +0.98 (c 0.51, CHCl3); 1H NMR
(270 MHz, CDCl3) δ 1.78, 1.94 (s, 3 H each), 2.87 (t, J ) 7.0, 2
H), 3.10 (dd, J ) 2.4, 10.3, 1 H), 3.16 (dd, J ) 4.9, 10.3, 1 H),
3.44-3.51 (m, 1 H), 3.50 (t, J ) 9.5, 1 H), 3.69 (dt, J ) 7.0, 9.5,
1 H), 4.01 (m, 2 H), 4.12 (dt, J ) 6.5, 9.5, 1 H), 4.39 (d, J ) 7.8,
1 H), 4.97-5.08 (m, 4 H), 5.11 (s, 2 H), 5.03-5.20 (m, 2 H), 5.73
(ddt, J ) 5.7, 10.5, 17.0, 1 H), 6.72 (dd, J ) 1.9, 8.1, 1 H), 6.82
(d, J ) 1.9, 1 H), 6.84 (d, J ) 8.1, 1 H), 7.15-7.47 (m, 25 H).
Anal. Calcd for C54H54O8: C, 75.15; H, 6.31. Found: C, 75.15;
H, 6.26.
2,4,6-Tr i-O-a cetyl-3-O-a llyl-r-D-glu cop yr a n osyl Ch lor id e
(3). To a solution of 214 (8.2 g, 21.11 mmol) in CH2Cl2 (14 mL)
were added R,R-dichloromethyl methyl ether (3.4 mL, 37.59
mmol) and a 2.2 M solution of ZnCl2‚Et2O (0.96 mL, 2.11 mmol)
in CH2Cl2 (0.77 mL) at 0 °C. The solution was stirred in the
dark at room temperature for 1 h, diluted with EtOAc, neutral-
ized with saturated aqueous NaHCO3 solution, and worked up
to give an oily residue. The residue was purified by column
chromatography using a solvent mixture of EtOAc/n-hexane (1:
2, v/v) to give 3 (7.7 g, 100%) as a colorless oil: [R]20 +136.10
D
(c 1.01, CHCl3); 1H NMR (270 MHz, CDCl3) δ 2.09, 2.10, 2.14 (s,
3 H each), 3.95 (t, J ) 9.6, 1 H), 4.05-4.30 (m, 2 H), 4.11 (dd, J
) 2.0, 12.4, 1 H), 4.21 (ddd, J ) 2.0, 4.2, 9.6, 1 H), 4.25 (dd, J )
4.2, 12.4, 1 H), 4.92 (dd, J ) 4.0, 9.6, 1 H), 5.10 (t, J ) 9.6, 1 H),
5.17 (ddt, J ) 1.3, 1.3, 10.6, 1 H), 5.23 (ddt, J ) 1.3, 1.3, 17.1, 1
H), 5.82 (ddt, J ) 5.3, 10.6, 17.1, 1 H), 6.29 (d, J ) 4.0, 1 H).
3,4-Di-O-ben zylp h en eth yl 2,4,6-Tr i-O-a cetyl-3-O-a llyl-â-
D-glu cop yr a n osid e (5a ). To a solution of 3 (8.8 g, 24.12 mmol)
in anhydrous ClCH2CH2Cl (62 mL) were added 3,4-di-O-ben-
zylphenethyl alcohol (4)17 (4.0 g, 11.96 mmol), Ag2CO3 (99 g,
359.02 mmol), and powdered molecular sieves (4 Å) at room
temperature. The reaction mixture was stirred overnight in the
dark at room temperature and filtered, and the filtrate was
condensed in vacuo. The residue was diluted with EtOAc,
washed with water, and worked up to give an oily residue.
Crystallization of the residue from EtOH afforded 5a (5.7 g, 72%)
as colorless crystals: mp 68-69 °C; [R]20D -10.79 (c 0.50, CHCl3);
1H NMR (270 MHz, CDCl3) δ 1.90, 2.06, 2.07 (s, 3 H each), 2.77
(t, J ) 6.8, 2 H), 3.50-3.61 (m, 2 H), 3.54 (t, J ) 9.5, 1 H), 3.99-
4.06 (m, 3 H), 4.11 (dd, J ) 2.7, 12.2, 1 H), 4.21 (dd, J ) 4.9,
12.2, 1 H), 4.34 (d, J ) 7.8, 1 H), 4.97 (dd, J ) 7.8, 9.5, 1 H),
5.04 (t, J ) 9.5, 1 H), 5.08-5.23 (m, 2 H), 5.11 (s, 2 H), 5.15 (d,
J ) 5.7, 2 H), 5.75 (ddt, J ) 5.7, 10.3, 17.0, 1 H), 6.69 (dd, J )
2.2, 8.4, 1 H), 6.81 (d, J ) 2.2, 1 H), 6.84 (d, J ) 8.4, 1 H), 7.24-
7.49 (m, 10 H). Anal. Calcd for C37H42O11‚0.15H2O: C, 67.06;
H, 6.39. Found: C, 66.81; H, 6.39.
3,4-Di-O-ben zylp h en eth yl 2,6-Di-O-a cetyl-3-O-a llyl-â-D-
glu cop yr a n osid e (9). To a stirred solution of 8 (4.6 g, 5.33
mmol) in 1,4-dioxane (47 mL) was added dropwise AcOH (93
mL). The reaction mixture was heated to 110 °C and stirred at
this temperature for 6 h. After being cooled to room temperature,
the reaction mixture was diluted with EtOAc, neutralized with
a saturated aqueous NaHCO3 solution, and worked up to give
an oily residue. The residue was purified by column chroma-
tography with elution first with CH2Cl2 and then with EtOAc/
n-hexane (1:2, v/v) to give 9 (2.6 g, 79%) as a colorless oil: [R]20
D
-29.29 (c 0.45, CHCl3); 1H NMR (270 MHz, CDCl3) δ 1.90, 2.09
(s, 3 H each), 2.76 (t, J ) 6.8, 2 H), 2.79 (d, J ) 3.2 1 H), 3.38 (t,
J ) 9.2, 1 H), 3.42 (ddd, J ) 2.2, 4.3, 9.2, 1 H), 3.48-3.57 (m,
1H), 3.54 (m, 1 H), 4.04 (dt, J ) 6.8, 9.2, 1 H), 4.17 (m, 2 H),
4.29 (dd, J ) 2.2, 11.9, 1 H), 4.32 (d, J ) 7.8, 1 H), 4.45 (dd, J
) 4.3, 11.9, 1 H), 4.89 (dd, J ) 7.8, 9.2, 1 H), 5.11 (s, 2 H), 5.15
(d, J ) 5.7, 2 H), 5.16 (ddt, J ) 1.6, 1.6, 10.3, 1 H), 5.24 (ddt, J
) 1.6, 1.6, 17.0, 1 H), 5.85 (ddt, J ) 5.7, 10.3, 17.0, 1 H), 6.69
(dd, J ) 1.9, 8.4, 1 H), 6.81 (d, J ) 1.9, 1 H), 6.84 (d, J ) 8.4, 1
H), 7.25-7.48 (m, 10 H). Anal. Calcd for C35H40O10: C, 67.73;
H, 6.50. Found: C, 67.45; H 6.53.
3,4-Di-O-ben zylp h en eth yl 2,6-Di-O-a cetyl-3-O-a llyl-4-O-
(3,4-di-O-ben zylcaffeoyl)-â-D-glu copyr an oside (11). A stirred
solution of 9 (2.6 g, 4.19 mmol), 3,4-di-O-benzylcaffeic acid (10)19
(2.2 g, 6.0 mmol), DCC (1.9 g, 9.21 mmol), DMAP (0.25 g, 2.05
mmol), and DMAP‚HCl (0.33 g, 2.05 mmol) in CH2Cl2 (410 mL)
was refluxed overnight. The reaction mixture was cooled to room
temperature and filtered through a plug of silica gel, and the
solvent was evaporated in vacuo. The residue was purified by
column chromatography with elution first with CH2Cl2 and then
with EtOAc/n-hexane (1:2, v/v) to give a colorless oil. Crystal-
lization of the oil from EtOH gave 11 (3.2 g, 79%) as light yellow
crystals: mp 139-140 °C; [R]20D -34.04 (c 0.51, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 1.91, 2.05 (s, 3 H each), 2.78 (t, J ) 7.1, 2
H), 3.54-3.61 (m, 1 H), 3.61-3.67 (m, 1 H), 3.63 (t, J ) 9.5, 1
H), 4.01-4.09 (m, 3 H), 4.15 (dd, J ) 3.2, 12.2, 1 H), 4.19 (dd, J
) 4.9, 12.2, 1 H), 4.38 (d, J ) 8.0, 1 H), 5.00 (dd, J ) 8.0, 9.5, 1
H), 5.12 (s, 2 H), 5.16 (d, J ) 8.4, 2 H), 5.18, 5.20 (s, 2 H each),
5.12-5.21 (m, 3 H), 5.71 (ddt, J ) 5.6, 10.4, 17.2, 1 H), 6.20 (d,
J ) 15.9, 1 H), 6.70 (dd, J ) 2.0, 8.0, 1 H), 6.82 (d, J ) 2.0, 1 H),
6.85 (d, J ) 8.0, 1 H), 6.92 (d, J ) 8.3, 1 H), 7.07 (dd, J ) 2.0,
8.3, 1 H), 7.11 (d, J ) 2.0, 1 H), 7.27-7.49 (m, 20 H), 7.59 (d, J
3,4-Di-O-ben zylp h en eth yl 3-O-Allyl-â-D-glu cop yr a n osid e
(6). To a solution of 5a (5 g, 7.55 mmol) in MeOH (35 mL) was
added dropwise 28% NaOMe in MeOH (2.3 mL) at 0 °C and the
mixture stirred at room temperature for 2 h before neutralization
with Dowex AG 50W-X8 (H+) resin. The resin was filtered off,
the filtrate was concentrated in vacuo, and the residue was
recrystallized from Et2O to give 6 (3.8 g, 94%) as colorless
crystals: mp 99-100 °C; [R]20 +1.85 (c 0.50, MeOH); 1H NMR
D
(270 MHz, CD3OD) δ 2.74 (t, J ) 7.3, 2 H), 3.08-3.19 (m, 2 H),
3.19-3.30 (m, 2 H), 3.55 (dd, J ) 5.4, 11.9, 1 H), 3.60 (m, 1 H),
3.75 (dd, J ) 1.9, 11.9, 1 H), 3.94 (dt, J ) 7.3, 9.5, 1 H), 4.81 (d,
J ) 7.3, 1 H), 4.22-4.27 (m, 2 H), 4.96 (s, 2 H), 5.00 (s, 2 H),
5.00 (m, 1 H), 5.20 (ddt, J ) 1.6, 1.6, 17.3, 1 H), 5.90 (ddt, J )
5.9, 10.3, 17.3, 1 H), 6.67 (dd, J ) 1.9, 8.4, 1 H), 6.81 (d, J ) 8.4,
1 H), 6.88 (d, J ) 1.9, 1 H), 7.13-7.36 (m, 10 H). Anal. Calcd for
C31H36O8‚0.4H2O: C, 69.39; H, 6.76. Found: C, 69.58; H, 6.86.
3,4-Di-O-b en zylp h en et h yl 3-O-Allyl-6-O-t r it yl-â-D-glu -
cop yr a n osid e (7). To a solution of 6 (3.7 g, 6.9 mmol) in
pyridine (41 mL) was added trityl chloride (7.7 g, 27.62 mmol)
at 0 °C. The solution was stirred overnight at room temperature
in the dark. The reaction mixture was evaporated in vacuo and
worked up to give an oily residue, which was purified by column
chromatography using a solvent mixture of EtOAc/n-hexane (1:2
to 1:1, v/v) to give 7 (4.6 g, 86%) as a colorless solid: [R]20D -22.6
) 15.9, 1 H). Anal. Calcd for C58H58O13
Found: C, 72.07; H, 6.09.
: C, 72.33; H, 6.07.
3,4-Di-O-ben zylp h en eth yl 2,6-Di-O-a cetyl-4-O-(3,4-d i-O-
ben zylca ffeoyl)-â-D-glu cop yr a n osid e (12). To a solution of
11 (2.7 g, 2.8 mmol) in 1,4-dioxane (92 mL) were added SeO2
(641 mg, 5.78 mmol) and AcOH (253 µL). The solution was then
stirred at 80 °C for 3 h. The reaction mixture was worked up to
give an oily residue, which was purified by column chromatog-
raphy using a solvent mixture of EtOAc/n-hexane (1:2 to 1:1,
1
(c 0.50, CHCl3); H NMR (270 MHz, CDCl3) δ 2.19 (d, J ) 1.9,
1 H), 2.67 (d, J ) 1.9, 1 H), 2.87 (t, J ) 7.0, 2 H), 2.37 (t, J )
8.9, 1 H), 3.32-3.46 (m, 4 H), 3.59 (dt, J ) 1.9, 8.9, 1 H), 3.63-
3.73 (m, 1 H), 4.07 (dt, J ) 7.0, 9.7, 1 H), 4.24 (d, J ) 7.6, 1 H),
4.28 (m, 1 H), 4.39 (m, 1 H), 5.05, 5.11 (s, 2 H each), 5.17 (m, 1
H), 5.29 (m, 1 H), 5.96 (ddt, J ) 5.7, 10.5, 17.0, 1 H), 6.72 (dd,
J ) 2.2, 8.4, 1 H), 6.81 (d, J ) 2.2, 1 H), 6.85 (d, J ) 8.4, 1 H),
7.17-7.46 (m, 25 H). Anal. Calcd for C50H50O8‚0.4H2O: C, 77.10;
H, 6.47. Found: C, 77.33; H, 6.53.
v/v) to give 12 (1.7 g, 66%) as a light yellow solid: [R]20 -22.30
D
(c 0.52, CHCl3); 1H NMR (270 MHz, CDCl3) δ 1.96, 2.05 (s, 3 H
each), 2.66 (d, J ) 5.9, 1 H), 2.79 (t, J ) 6.6, 2 H), 3.63 (m, 1 H),
3.63-3.74 (m, 1 H), 3.76 (dt, J ) 5.9, 9.5, 1 H), 4.06 (dt, J ) 6.5,
9.5, 1 H), 4.16-4.23 (m, 2 H), 4.42 (d, J ) 7.8, 1 H), 4.88 (dd, J
) 7.8, 9.5, 1 H), 5.03 (t, J ) 9.5, 1 H), 5.12 (s, 2 H), 5.15 (d, J )
3.5, 2 H), 5.16, 5.19 (s, 2 H each), 6.21 (d, J ) 15.9, 1 H), 6.71
(dd, J ) 1.9, 8.1, 1 H), 6.82 (d, J ) 1.9, 1 H), 6.85 (d, J ) 8.1, 1
H), 6.91 (d, J ) 8.4, 1 H), 7.06 (dd, J ) 1.9, 8.4, 1 H), 7.11 (d, J
) 1.9, 1 H), 7.25-7.48 (m, 20 H), 7.61 (d, J ) 15.9, 1 H). Anal.
Calcd for C55H54O13‚0.45H2O: C, 71.55; H, 5.90. Found: C, 71.31;
H, 5.83.
3,4-Di-O-ben zylp h en eth yl 2,4-Di-O-a cetyl-3-O-a llyl-6-O-
tr ityl-â-D-glu cop yr a n osid e (8). To a solution of 7 (4.6 g, 5.91
mmol) in pyridine (33 mL) was added acetic anhydride (28 mL)
at 0 °C. This solution was stirred overnight at room temperature
and concentrated to give an oily residue. The residue was
suspended in EtOAc, neutralized with saturated aqueous NaH-
3,4-Di-O-ben zylp h en eth yl 2,6-Di-O-a cetyl-3-O-(2,3,4-tr i-
O-a cet yl-r-L-r h a m n op yr a n osyl)-4-O-(3,4-d i-O-b en zylca f-