Page 5 of 8
Organic & Biomolecular Chemistry
stirred for 10 min at rt. The solid was filtered off and rinsed
successively with water (10 mL), MeOH (3 mL), and water (10 mL).
The solid was collected and dried in vacuo for 16 h to afford the title
compound (3.3 g, 92% yield) as a brown solid. The title compound
(d, 1H, J1,2 = 1.9 Hz, H-1), 7.11-7.51 (m, 24H, aromatic) ppm; 13C-
NMR (75 MHz): δ, 68.90, 72.68, 72.97, 73.51, 73.64, 74.21, 75.01,
75.36, 79.21, 99.56, 110.04, 118.66, 123.36 (x 2), 124.60 (x 2),
127.66 (x 2), 127.97 (x 2), 128.03 (x 2), 128.14 (x 2), 128.22 (x 2),
5 can be stored for extended period of time but was additionally dried 75 128.47 (x 2), 128.55 (x 2), 137.89 (x 2), 138.29 (x 2), 138.43 (x 2),
for 4-5 h directly prior to application. Analytical data for AgOBox:
1H-NMR (300 MHz): δ, 6.77 (t, 1H, aromatic), 6.95 (m, 3H,
aromatic); 13C-NMR (75 MHz): δ, 107.2, 111.5, 118.3, 121.9, 142.5,
146.4, 163.3; UV: λmax = 274, 280 nm.
138.47 (x 2), 141.03, 148.54, 161.60; HR-FAB MS [M+Na]+
calculated for C41H39NO7Na+ 680.2624, found 680.2626.
3,4,6-Tri-O-acetyl-1,2-O-(1-benzoxazolyloxyethylidene)-α-D-
glucopyranose (8).
A mixture of 2,3,4,6-tetra-O-acetyl-α-D-
10 Synthesis of OBox glycosyl donors
80 glucopyranosyl bromide27 (7, 0.5 g, 1.2 mmol) and freshly activated
molecular sieves (3 Å, 1.5 g) in dry CH2Cl2 (5.0 mL) was stirred
under argon for 1 h at rt. After that, AgOBox (0.59 g, 2.43 mmol)
Benzoxazolyl 2,3,4,6-tetra-O-acetyl-α,β-D-glucopyranoside (2). 2-
Chlorobenzoxazole (79.5 μL, 0.7 mmol) and DBU (0.14 mL, 0.93
mmol) were added to a stirring solution of 2,3,4,6-tetra-O-acetyl-α,β-
D-glucopyranose25 (1, 0.16 g, 0.46 mmol) in dry CH2Cl2 (1.6 mL)
o
was added and the resulting mixture was stirred for 1.5 h at 40 C.
The solid was filtered off and rinsed successively with CH2Cl2. The
85 combined filtrate (~100 mL) was washed with 1% aq. NaOH (2 x 40
mL), water (2 x 40 mL), and brine (40 mL). The organic phase was
separated, dried with MgSO4, and concentrated in vacuo. The residue
was purified by column chromatography on silica gel (ethyl acetate-
hexanes gradient elution) to afford the title compound (447 mg, 79%
90 yield) as a pale-yellow foam. Analytical data for 8: Rf = 0.5 (ethyl
acetate/hexanes, 1/1, v/v); [α]D26 -3.7 (c = 1.0, CHCl3); 1H-NMR (300
MHz): δ, 2.08, 2.10, 2.13, 2.15 (4 s, 12H, 4 x COCH3), 4.06 (m, 1H,
H-5), 4.25-4.28 (m, 3H, J2,3 = 2.4 Hz, H-2, 6a, 6b), 4.95 (dd, 1H, J4,5
o
15 and the resulting mixture was stirred for 2 h at 0 C. After that, the
solid was filtered off and washed successively with CH2Cl2. The
combined filtrate (~60 mL) was washed with 1% aq. NaOH (2 x 20
mL), water (20 mL), and brine (20 mL). The organic phase was
separated, dried with MgSO4, and concentrated in vacuo. The residue
20 was purified by column chromatography on silica gel (ethyl acetate -
hexane gradient elution) to obtain the title compound (187 mg, 85%
yield) as a white foam. Analytical data for α-2: Rf = 0.42 (ethyl
22
acetate/hexanes, 1/1, v/v); [α]D +84.5 (c= 1.0, CHCl3); 1H-NMR
= 9.5 Hz, H-4), 5.32 (dd, 1H, J3,4 = 2.4 Hz, H-3), 5.82 (d, 1H, J1,2
=
95 5.3 Hz, H-1), 7.10-7.47 (m, 4H, aromatic) ppm; 13C-NMR (75 MHz):
δ, 20.7, 20.8, 20.9, 22.4, 63.0, 67.3, 68.0, 69.3, 73.1, 97.5, 110.2,
111.7, 113.5, 124.0, 124.4, 129.4, 142.5, 151.6, 169.0, 169.7, 170.7
ppm; UV: λmax = 274, 280 nm; HR-FAB MS [M+Na]+ calculated for
C21H23NO11Na+ 488.1168, found 488.1170.
(300 MHz): δ, 2.04-2.11 (m, 12H, 4 x COCH3), 4.13 (m, 1H, H-6a),
25 4.30 (m, 2H, H-5, 6b), 5.25 (m, 2H, J2,3 = 9.9 Hz, J4,5 = 3.5 Hz, H-2,
4), 5.70 (dd, 1H, J3,4 = 9.9 Hz, H-3), 6.57 (d, 1H, J1,2 = 3.5 Hz, H-1),
7.20-7.50 (m, 4H, aromatic), 7.44 (d, 1H, aromatic), 7.21-7.50 (m,
4H, aromatic) ppm; 13C-NMR (75 MHz): δ, 22.7 (x 4), 61.2, 67.6,
69.3, 69.5, 70.1, 96.7, 110.2, 118.6, 123.6, 124.7, 140.4, 148.4, 161.5,
30 169.4, 169.9, 170.1, 170.6; UV: λmax = 273, 279 nm; HR-FAB MS 100 Benzoxazolyl 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranoside (10).
[M+Na]+ calculated for C21H23NO11Na+ 488.1168, found 488.1168.
A mixture of 2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl bromide29
(9, 0.4 g, 0.56 mmol) and freshly activated molecular sieves (3 Å, 1.2
g) in dry CH2Cl2 (4.0 mL) was stirred under argon for 1 h at rt. After
that, AgOBox (0.20 g, 0.84 mmol), 2,6-lutidine (0.09 g, 0.84 mmol),
105 and tetrabutylammonium iodide (TBAI, 0.012 g, 0.033 mmol) were
added and the resulting mixture was stirred for 10 h at rt. The solid
was filtered off and rinsed successively with CH2Cl2. The combined
filtrate (~60 mL) was washed with 1% aq. NaOH (2 x 20 mL), water
(2 x 20 mL), and brine (20 mL). The organic phase was separated,
110 dried with MgSO4, and concentrated in vacuo. The residue was
purified by column chromatography on silica gel (ethyl acetate-
hexanes gradient elution) to afford the title compound (0.36 g, 83%
yield) as a pale-yellow amorphous solid. Analytical data for 10: Rf =
0.46 (ethyl acetate/hexanes, 2/3, v/v); [α]D26 +35.9 (c= 1.0, CHCl3);
115 1H-NMR (300 MHz): δ, 4.50 (m, 2H, J5,6a = 3.2 Hz, H-5, 6a), 4.70
(dd, 1H, J5,6b = 1.5 Hz, H-6b), 5.76 (m, 1H, J2,3 = 5.5 Hz, H-2), 5.87
(dd, 1H, J4,5 = 4.6 Hz, H-4), 6.03 (dd, 1H, J3,4 = 9.2 Hz, H-3), 6.38 (d,
1H, J1,2 = 7.6 Hz, H-1), 7.15-7.92 (m, 24H, aromatic), ppm; 13C-
NMR: δ, 62.6, 68.9, 70.9, 72.5, 73.4, 98.7, 110.2, 118.5, 123.6 (x 2),
120 124.6 (x 2), 128.4 (x 2), 128.4 (x 2), 128.5 (x 4), 128.6, 129.5, 129.8
(x 2), 129.9 (x 4), 130.0 (x 2), 133.1, 133.5, 133.6 (x 2), 140.4, 148.5,
161.6, 164.9, 165.1, 165.7, 166.1 ppm; HR-FAB MS [M+Na]+
calculated for C41H31NO11Na+ 736.1795, found 736.1794.
Benzoxazolyl 2,3,4,6-tetra-O-benzyl-α/β-D-glucopyranoside (4).
2-Chlorobenzoxazole (0.2 g, 1.9 mmol) and KOH (0.021 g, 0.37
mmol) were added to a stirring solution of 2,3,4,6-tetra-O-benzyl-
35 α/β-D-glucopyranose (3, 0.2 g, 0.37 mmol) in acetone (4.0 mL) and
o
the resulting mixture was stirred for 3 h at 0 C. After that, the solid
was filtered off and washed successively with CH2Cl2. The combined
filtrate (~60 mL) was washed with water (3 x 20 mL). The organic
phase was separated, dried with MgSO4, and concentrated in vacuo.
40 The residue was purified by column chromatography on silica gel
(ethyl acetate – hexanes gradient elution) to obtain the title compound
(195 mg, 80% yield, α/β = 2.5/1) as a colorless syrup. Analytical data
for α-4: Rf = 0.43 (ethyl acetate/hexanes, 1/4, v/v); 1H-NMR (300
MHz): δ, 3.61 (dd, 1H, J5,6a = 1.6 Hz, J6a,6b = 11.0 Hz, H-6a), 3.77 (m,
45 3H, H-2, 4, 6b), 4.00 (m, 1H, H-5), 4.11 (dd, 1H, J3,4 = 9.4 Hz, H-3),
4.48 (dd, 2H, 2J = 12.0 Hz, CH2Ph), 4.67 (dd, 2H, 2J = 10.7 Hz,
2
CH2Ph), 4.73 (s, 2H, CH2Ph), 4.90 (dd, 2H, J = 10.9 Hz, CH2Ph),
6.47 (d, 1H, J1,2 = 3.3 Hz, H-1), 7.17-7.31 (m, 24H, aromatic) ppm;
13C-NMR (75 MHz): δ, 68.1, 73.5, 73.7 (x 2), 75.4, 76.0, 76.8, 79.2,
50 81.6, 98.8, 110.0, 118.6, 123.2, 124.5, 127.9 (x 2), 128.0 (x 3), 128.1
(x 4), 128.2 (x 2), 128.6 (x 9), 137.6, 138.0, 138.3, 138.8, 141.0,
148.4, 162.3; UV: λmax = 270, 276 nm; HR-FAB MS [M+Na]+
calculated for C41H39NO7Na+ 680.2624, found 680.2624.
Benzoxazolyl 2,3,4,6-tetra-O-benzoyl-β-D-galactopyranoside (12).
125 A
mixture
of
2,3,4,6-tetra-O-benzoyl-α-D-galactopyranosyl
Benzoxazolyl 2,3,4,6-tetra-O-benzyl-α-D-mannopyranoside (6). 2-
55 Chlorobenzoxazole (0.056 g, 0.37 mmol) and KOH (0.054 g, 0.96
mmol) were added to a stirring solution of 2,3,4,6-tetra-O-benzyl-D-
mannopyranose26 (5, 0.2 g, 0.37 mmol) in acetone (4.0 mL) and the
resulting mixture was stirred for 2 h at 0 oC. After that, the solid was
filtered off and washed successively with CH2Cl2. The combined
60 filtrate (~60 mL) was washed with water (3 x 20 mL). The organic
phase was separated, dried with MgSO4, and concentrated in vacuo.
The residue was purified by column chromatography on silica gel
(ethyl acetate - hexanes gradient elution) to obtain the title compound
(122 mg, 50 % yield) as a colorless syrup. Analytical data for 6: Rf =
bromide30 (11, 0.2 g, 0.28 mmol) and freshly activated molecular
sieves (3 Å, 0.6 g) in dry CH2Cl2 (2.0 mL) was stirred under argon
for 1 h at rt. After that, AgOBox (0.1 g, 0.42 mmol), 2,6-lutidine
(0.045 g, 0.42 mmol), TBAI (0.006 g, 0.016 mmol) were added and
130 the resulting mixture was stirred for 3 h at rt. The solids were filtered
off and rinsed successively with CH2Cl2. The combined filtrate (~40
mL) was washed with 1% aq. NaOH (2 x 10 mL), water (2 x 10 mL),
and brine (10 mL). The organic phase was separated, dried with
MgSO4, and concentrated in vacuo. The residue was purified by
135 column chromatography on silica gel (ethyl acetate-hexanes gradient
elution) to afford the title compound (177 mg, 82% yield) as a yellow
foam. Analytical data for 12: Rf = 0.50 (ethyl acetate/hexanes, 2/3,
v/v); [α]D26 +81.5 (c = 1.0, CHCl3); 1H-NMR (300 MHz): δ, 4.51 (m,
1H, J5,6a = 5.2 Hz, J6a,6b = 9.6 Hz, H-6a), 4.68 (m, 2H, J5,6b = 6.8 Hz,
140 H-5, 6b), 5.78 (dd, 1H, J3,4 = 3.4 Hz, H-3), 6.14 (m, 2H, J2,3 = 10.2
Hz, H-2, 4), 6.39 (d, 1H, J1,2 = 8.0 Hz, H-1), 7.19-8.13 (m, 24H,
21
65 0.4 (ethyl acetate/hexanes, 1/4, v/v); [α]D +36.2 (c= 1.0, CHCl3);
1H-NMR (300 MHz): δ, 3.65 (dd, 1H, J5,6b =1.8 Hz, J6a,6b = 11.2 Hz,
H-6b), 3.74 (dd, 1H, J5,6a = 4.4 Hz, H-6a), 3.90-3.97 (m, 3H, J3,4
=
9.4 Hz, H-2, 3, 5), 4.09 (dd, 1H, J4,5 = 9.4 Hz, H-4), 4.50 (dd, 2H, 2J
2
= 12.0 Hz, CH2Ph), 4.54 (dd, 2H, J = 11.7 Hz, CH2Ph), 4.65 (dd,
70 2H, 2J = 10.8 Hz, CH2Ph), 4.74 (dd, 2H, 2J = 12.3 Hz, CH2Ph), , 6.36
This journal is © The Royal Society of Chemistry [year]
Org. Biomol. Chem., [year], [vol], 00–00 | 5