Bosse et al.
mmol) in CH2Cl2 (10 mL) was added trichloroacetonitrile (5
mL) and DBU (10 µL). The mixture was stirred at room
temperature for 2 h and then concentrated. Purification of the
crude residue by flash chromatography (4:1 hexanes/EtOAc)
yielded 461 mg (70%) of 30 as a colorless foam. [R]D: +65.1 (c
) 0.83, CH2Cl2). IR (thin film): 2926, 1717, 1684, 1558, 1494,
1452, 1403, 1050 cm-1. 1H NMR (400 MHz, CDCl3): δ 8.73 (s,
1 H), 7.39-7.27 (m, 10 H), 6.93 (d, J ) 8.9 Hz, 1 H), 6.47 (d,
J ) 3.5 Hz, 1 H), 5.42 (dd, J ) 11.3, 2.7 Hz, 1 H), 4.90-4.87
(m, 1 H), 4.82 (d, J ) 11.4 Hz, 1 H), 4.62 (d, J ) 11.4 Hz, 1 H),
4.52-4.49 (m, 2 H), 4.44 (d, J ) 11.7 Hz, 1 H), 4.25 (dd, J )
7.8, 5.7 Hz, 1 H), 4.12 (d, J ) 2.4 Hz, 1 H), 3.70 (app t, J ) 9.0
Hz, 1 H), 3.61 (dd, J ) 9.1, 5.4 Hz, 1 H), 2.06 (s, 3 H). 13C
NMR (100 MHz, CDCl3): δ 171.86, 162.44, 160.67, 138.06,
137.94, 128.89, 128.87, 128.58, 128.39, 128.34, 128.28, 95.32,
92.46, 91.22, 77.64, 75.65, 74.06, 73.92, 72.47, 70.95, 67.80,
50.92, 21.28. ESI-MS: m/z (M + Na)+ calcd 710.9763, obsd
710.9763.
zyl-r-D-ga la ctop yr a n osyl-(1f4)-3,6-d i-O-ben zyl-2-O-p iv-
a loyl-â-D-ga la ct op yr a n osyl-(1f4)-3,6-d i-O-b en zyl-2-O-
p iva loyl-â-D-glu cop yr a n osid e 32. Trisaccharide 31 (308 mg,
0.230 mmol) and glycosyl phosphate 5 (196 mg, 0.270 mmol)
were coevaporated three times with toluene, dissolved in
CH2Cl2 (4 mL), and cooled to -78 °C. TMSOTf (50 µL, 0.270
mmol) was added and the mixture was stirred for 30 min.
Triethylamine (200 µL) was added and the mixture was
directly purified by flash chromatography (4:1 f 2:1 hexane/
EtOAc) to afford 405 mg (93%) of 32 as a white solid. [R]D:
-15.2 (c ) 1.00, CH2Cl2). IR (thin film): 1734, 1521, 1455,
1
1364, 1231, 1093 cm-1. H NMR (400 MHz, CDCl3): δ 7.46-
7.18 (m, 45 H), 6.54 (d, J ) 9.8 Hz, 1 H), 5.85-5.78 (m, 1 H),
5.36 (dd, J ) 9.9, 8.3 Hz, 1 H), 5.06-4.96 (m, 4 H), 4.84-4.74
(m, 6 H), 4.66-4.47 (m, 8 H), 4.38-4.02 (m, 17 H), 4.02-3.99
(m, 2 H), 3.89 (app s, 1 H), 3.90-3.80 (m, 2 H), 3.78-3.51 (m,
3 H), 3.48-3.35 (m, 4 H), 3.28 (app d, J ) 10.2 Hz, 1 H), 3.05
(dd, J ) 8.5, 5.1 Hz, 1 H), 2.12-2.08 (m, 2 H), 2.00 (s, 3 H),
1.71-1.66 (m, 2 H), 1.18 (s, 9 H), 1.26 (s, 9 H). 13C NMR (100
MHz, CDCl3): δ 171.27, 171.13, 163.83, 162.32, 139.08, 138.55,
138.50, 138.46, 138.43, 138.37, 129.72, 129.15, 129.04, 128.93,
128.89, 128.86, 128.83, 128.65, 128.63, 128.45, 128.40, 128.29,
128.25, 128.21, 128.15, 128.13, 128.03, 127.94, 127.92, 127.85,
127.80, 127.57, 127.42, 115.26, 102.34, 101.73, 101.00, 92.84,
80.41, 80.00, 79.64, 77.72, 77.64, 75.48, 75.39, 75.27, 75.15,
74.89, 74.24, 73.96, 73.93, 73.85, 73.80, 73.61, 73.50, 73.38,
73.04, 73.01, 72.33, 72.16, 71.84, 71.76, 69.34, 69.13, 68.48,
68.17, 67.93, 67.64, 53.65, 39.19, 39.09, 30.49, 29.21, 27.76,
27.67, 27.58, 21.32. ESI-MS: m/z (M + Na)+ calcd 1920.7315,
obsd 1920.7340.
Dibu tyl 3-O-Acetyl-4,6-di-O-ben zyl-2-deoxy-2-tr ich lor o-
a ceta m id o-â-D-ga la ctop yr a n osyl P h osp h a te 5. To a solu-
tion of imidate 30 (453 mg, 0.66 mmol) in CH2Cl2 (5 mL) at 0
°C was added dibutyl phosphate (150 µL, 0.72 mmol). The
mixture was stirred for 1 h and then directly loaded onto a
short column of silica gel and eluted with 1:1 hexanes/EtOAc
to afford 360 mg (74%) of phosphate 5 as a white solid. [R]D:
+13.8 (c ) 0.82, CH2Cl2). IR (thin film): 2928, 1718, 1540,
1
1494, 1454, 1260, 1028 cm-1. H NMR (400 MHz, CDCl3): δ
8.08 (d, J ) 9.5 Hz, 1 H), 7.35-7.26 (m, 10 H), 5.53 (app t, J
) 7.8 Hz, 1 H), 5.25 (d, J ) 10.9 Hz, 1 H), 4.71 (d, J ) 11.6
Hz, 1 H), 4.63-4.55 (m, 1 H), 4.50 (d, J ) 11.2 Hz, 1 H), 4.47
(d, J ) 10.9 Hz, 1 H), 4.38 (d, J ) 11.7 Hz, 1 H), 4.09 (m, 2 H),
4.02-3.99 (m, 2 H), 3.82 (app s, 2 H), 3.64-3.60 (m, 1 H), 3.53-
3.49 (m, 1 H), 2.01 (s, 3 H), 1.64-1.59 (m, 4 H), 1.38-1.36 (m,
n -P en ten yl 4,6-Di-O-ben zyl-2-d eoxy-2-tr ich lor oa cet-
a m id o-â-D-ga la ct op yr a n osyl-(1f3)-2,4,6-t r i-O-b en zyl-r-
D-ga la ct op yr a n osyl-(1f4)-3,6-d i-O-b en zyl-2-O-p iva loyl-
â-D-ga la ctop yr a n osyl-(1f4)-3,6-d i-O-ben zyl-2-O-p iva loyl-
â-D-glu cop yr a n osid e 33. To a solution of tetrasaccharide 32
(305 mg, 0.160 mmol) in MeOH (15 mL) was added a solution
of NaOMe in MeOH (180 µL, 0.80 mmol, 25% by wt). The
reaction mixture was stirred at room temperature for 1 h and
then quenched with Dowex 50-X8 ion-exchange resin, filtered,
and concentrated. The crude residue was purified by flash
chromatography (3:1 hexanes/EtOAc) to afford 262 mg (88%)
of tetrasaccharide 33 as a white solid. [R]D: -6.6 (c ) 1.10,
4 H), 0.94-0.88 (m, 6 H). 13C NMR (100 MHz, CDCl3):
δ
170.41, 163.73, 162.42, 137.60, 128.35, 128.29, 128.19, 127.82,
127.70, 127.53, 96.77, 96.72, 92.62, 91.97, 74.92, 73.31, 73.04,
72.81, 68.34, 68.27, 68.14, 68.10, 68.03, 67.66, 52.72, 52.63,
31.93, 31.86, 20.68, 18.49, 18.46, 13.49. 31P NMR (120 MHz,
CDCl3): δ -2.62. ESI-MS: m/z (M + Na)+ calcd 760.1582, obsd
760.1559.
n -P en t en yl 2,4,6-Tr i-O-b en zyl-r-D-ga la ct op yr a n osyl-
(1f4)-3,6-d i-O-ben zyl-2-O-p iva loyl-â-D-ga la ctop yr a n osyl-
(1f4)-3,6-d i-O-b e n zyl-2-O-p iva loyl-â-D -glu cop yr a n o-
sid e 31. Trisaccharide 22 (1.10 g, 0.746 mmol) was dissolved
in CH2Cl2 (20 mL). A solution of hydrazine acetate (122 mg,
1.33 mmol) in MeOH (4 mL) was added and the mixture was
stirred for 12 h. The mixture was diluted with CH2Cl2 (100
mL) and washed twice with water, dried over MgSO4, filtered,
and concentrated under reduced pressure. The residue was
purified by flash chromatography (4:1 f 2:1 hexane/EtOAc)
to afford 634 mg (62%) of 31 as a colorless oil. [R]D: +25.1 (c
) 1.00, CH2Cl2). IR (thin film): 3030, 2871, 1737, 1130, 1094
CH2Cl2). IR (thin film): 2870, 1735, 1454, 1366, 1094 cm-1
.
1H NMR (400 MHz, CDCl3): δ 7.45-7.18 (m, 45 H), 6.37 (d, J
) 8.7 Hz, 1 H), 5.86-5.76 (m, 1 H), 5.37 (app t, J ) 8.2 Hz, 1
H), 5.04-4.90 (m, 5 H), 4.80-4.65 (m, 6 H), 4.56-4.30 (m, 8
H), 4.24 (app s, 1 H), 4.16-4.00 (m, 11 H), 3.86-3.67 (m, 6
H), 3.66-3.57 (m, 2 H), 3.44-3.28 (m, 5 H), 3.17 (app d, J )
10.5 Hz, 1 H), 3.08 (dd, J ) 8.3, 5.4 Hz, 1 H), 2.34 (br s, 1 H),
1.87-1.89 (m, 2 H), 1.88 (s, 9 H), 1.69-1.64 (m, 2 H), 1.13 (s,
9 H). 13C NMR (100 MHz, CDCl3): δ 176.84, 176.81, 139.44,
139.31, 138.79, 138.31, 138.24, 138.20, 138.15, 138.09, 129.44,
128.72, 128.66, 128.61, 128.58, 128.38, 128.24, 128.18, 128.09,
128.04, 127.97, 127.93, 127.86, 127.73, 127.66, 127.60, 127.38,
127.25, 114.98, 101.66, 101.43, 100.30, 100.07, 92.47, 79.83,
79.59, 79.20, 75.61, 75.51, 75.27, 75.14, 73.78, 73.71, 73.64,
73.48, 73.36, 73.17, 72.93, 72.81, 72.30, 71.64, 71.42, 69.03,
68.26, 67.87, 67.85, 67.42, 56.52, 38.93, 38.83, 30.22, 28.94,
28.30, 27.52, 27.32, 22.89, 14.43. ESI-MS: m/z (M + Na)+ calcd
1878.7209, obsd 1878.7262.
cm-1 1H NMR (400 MHz, CDCl3): δ 7.37-7.16 (m, 35 H),
.
5.83-5.67 (m, 1 H), 5.27 (dd, J ) 10.4, 7.9 Hz, 1 H), 5.14 (d,
J ) 11.9 Hz, 1 H), 5.04-4.94 (m, 4 H), 4.78 (d, J ) 12.2 Hz, 1
H), 4.77 (d, J ) 12.1 Hz, 1 H), 4.66 (d, J ) 11.3 Hz, 1 H), 4.56-
4.45 (m, 6 H), 4.38-4.34 (m, 2 H), 4.24-4.20 (m, 3 H), 4.12-
3.99 (m, 5 H), 3.96-3.95 (m, 1 H), 3.88-3.81 (m, 1 H), 3.73-
3.79 (m, 3 H), 3.62 (app t, J ) 9.0 Hz, 1 H), 3.50-3.34 (m, 5
H), 3.27 (dd, J ) 10.4, 2.5 Hz, 1 H), 3.07 (dd, J ) 8.8, 4.9 Hz,
1 H), 2.12-2.05 (m, 2 H), 1.78-1.62 (m, 3 H), 1.17 (s, 9 H),
1.12 (s, 9 H). 13C NMR (100 MHz, CDCl3): δ 176.90, 176.74,
139.44, 139.01, 138.62, 138.36, 138.32, 138.29, 138.24, 138.13,
128.61, 128.42, 128.39, 128.31, 128.28, 128.21, 128.17, 128.11,
127.92, 127.86, 127.75, 127.68, 127.60, 127.46, 127.30, 127.16,
114.96, 101.47, 100.19, 99.94, 81.35, 80.03, 75.40, 75.33, 75.30,
74.60, 74.48, 73.68, 73.51, 73.31, 73.12, 73.12, 72.36, 71.75,
71.30, 70.09, 69.08, 68.94, 68.30, 67.69, 67.55, 30.23, 28.93,
28.93, 27.25. ESI-MS: m/z (M + Na)+ calcd 1393.6645, obsd
1393.6612.
Dibu tyl 2-O-Acetyl-3,4,6-tr i-O-ben zyl-â-D-ga la ctop yr a n -
osyl P h osp h a t e 6. Tri-O-benzyl galactal 12 (644 mg, 1.55
mmol) was dissolved in CH2Cl2 (15 mL) and cooled to 0 °C.
DMDO (0.08 M in acetone, 30 mL, 2.4 mmol) was added and
the reaction was stirred for 10 min. The solvent was evapo-
rated at 0 °C, and the resulting residue was dissolved in
CH2Cl2 (15 mL) and cooled to -78 °C. Dibutyl phosphate (340
µL, 1.7 mmol) was added and the mixture was stirred for 10
min. After warming to 0 °C DMAP (758 mg, 6.20 mmol) and
acetyl chloride (220 µL, 3.10 mmol) were added, and the
reaction mixture was stirred for 2 h and concentrated.
Purification of the crude residue by flash chromatography (1:1
n -P en ten yl 3-O-Acetyl-4,6-di-O-ben zyl-2-deoxy-2-tr ich lo-
r oa ceta m id o-â-D-ga la ctop yr a n osyl-(1f3)-2,4,6-tr i-O-ben -
6668 J . Org. Chem., Vol. 67, No. 19, 2002