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S. Anjum et al. / Tetrahedron 69 (2013) 816e825
4.9. 3-Azido-1,2,4,6-tetra-O-benzyl-3-deoxy-
a/b
-D
-glucopyr-
4.12. 6-O-Acetyl-3-azido-2,4-di-O-benzyl-3-deoxy-a/b-D-glu-
anose (9)
copyranosyl trichloroacetimidate (12)
A
solution of 3-azido-3-deoxy-
a
/
b
-
D
-glucopyranose (3)
Following the general procedure for trichloroacetimidation, 11
(1.29 g, 3.04 mmol) in DCM (20.0 mL), trichloroacetonitrile
(3.05 mL, 30.4 mmol) and Cs2CO3 (0.099 g, 0.304 mmol) were
reacted for 3 h. Purification by flash chromatography with 15e20%
EtOAc in hexane gave 12 as a colorless gum (1.6 g, 92%). 1H NMR
(200 mg, 0.975 mmol) in DMF (5 mL) was cooled to 0 ꢁC and NaH
(60% dispersion, 215 mg, 5.36 mmol) was added in five portions
with stirring at the same temperature. After 10 min, benzyl bro-
mide (0.695 mL, 5.36 mmol) was added dropwise, and the reaction
was stirred a further 2 h. The reaction was quenched with MeOH
(3 mL), followed by addition of water (50 mL). The solution was
extracted with DCM (50 mLꢂ3), dried over anhydrous Na2SO4, and
concentrated to a colorless oil. Flash chromatography eluting with
25% EtOAc in hexane resulted in isolation of 9 as a colorless gum
(CDCl3, a/b 0.8:1.0): d 8.77 (s, 1HNHb), 8.66 (s, 0.8HNHa), 7.41e7.28
(m, 18H), 6.44 (d, J¼3.5 Hz, 0.8H1a), 5.79 (d, J¼8.0 Hz, 1H1b), 4.96 (d,
J¼11.0 Hz, 1H), 4.89 (t, J¼11.0 Hz, 1.8H), 4.79 (d, J¼11 Hz, 1H), 4.73
(m,1.8H), 4.60 (dd, J¼11.0, 6.5 Hz,1.8H), 4.32 (m,1H), 4.28 (m, 2.4H),
4.05 (m, 1.8H), 3.68 (m, 1.8H), 3.60 (m, 1.8H), 3.43 (m, 1.8H), 2.06 (m,
(522 mg, 95% yield). 1H NMR (CDCl3,
a
/b
ratio 1.0:1.0):
d
7.38 (m,
5.4H). 13C NMR (CDCl3):
d 170.8, 170.7, 163.4, 163.3, 137.5, 137.2,
40H), 5.00 (d, J¼12 Hz, 1H1b), 4.95 (d, J¼11 Hz, 1H1a), 4.83 (m, 2H),
4.76 (d, J¼11 Hz, 2H), 4.67 (m, 5H), 4.60e4.45 (m, 7H), 4.0 (t,
J¼10 Hz,1H), 3.80e3.70 (m, 4H), 3.58 (m, 2H), 3.48 (m, 3H), 3.39 (m,
137.1, 137.0, 128.8e128.0 (20C), 97.5, 90.3, 80.7, 78.1, 75.8, 75.8, 75.0,
74.9, 74.6, 73.7, 73.2, 68.6, 68.3, 65.1, 62.8, 62.8, 20.9, 20.8. HRFABMS
m/z 571.0911 [MþHþ] (calcd for C24H25Cl3N4O6, 571.0918).
2H). 13C NMR (CDCl3):
d 138.0, 137.8, 137.7, 137.7, 137.6, 137.6, 137.3,
137.0, 129.0e125.0 (40C), 102.6, 94.9, 80.0, 77.8, 76.4, 76.3, 75.5,
74.9, 74.8, 74.7, 74.6, 73.6, 72.8, 71.2, 70.1, 69.3, 68.6, 68.5, 68.1,
65.5. HRFABMS m/z 565.2648 [MþHþ] (calcd for C34H35N3O5,
565.2655).
4.13. 6-O-Acetyl-3-azido-2,4-di-O-benzyl-3-deoxy-
pyranosyl-(1/10)-20,40,60-tri-O-acetyl-30-azido-30-deoxy-
glucopyranoside (13), 6-O-acetyl-3-azido-2,4-di-O-benzyl-3-
deoxy-
-glucopyranosyl-(1/10)-20,40,60-tri-O-acetyl-30-az-
ido-30-deoxyL
-glucopyranoside (14), 6-O-acetyl-3-azido-
2,4-di-O-benzyl-3-deoxy-
-glucopyranosyl-(1/10)-20,40,60-
tri-O-acetyl-30-azido-30-deoxy-
-glucopyranoside (15), 6-O-
a-D-gluco-
b-D-
a-D
a-D
b-D
4.10. 1,6-Di-O-acetyl-3-azido-2,4-di-O-benzyl-3-deoxy-
a
/b-
D-
b-D
glucopyranose (10)
acetyl-3-azido-2,4-di-O-benzyl-3-deoxy-a-D-glucopyranosyl
trichloroacetamide (16)
A suspension of 3-azido-1,2,4,6-tetra-O-benzyl-3-deoxy-
a
/
b
-
D
-
glucopyranose (9) (0.5 g, 0.884 mmol) in acetic anhydride (2.0 mL)
was added in one portion to a 2% solution of sulfuric acid in acetic
anhydride (2.6 mL). The reaction mixture was stirred for 5 min at
room temperature then poured into 50 mL ice water. The aqueous
phase was extracted successively with EtOAc, and the organic
extracts washed with saturated NaHCO3 and brine; dried over
anhydrous Na2SO4, and concentrated in vacuo. The resulting col-
orless gum was purified via flash chromatography, eluted with
25e30% EtOAc:hexane to isolate 10 (304.4 mg, 70%). 1H NMR
The general glycosylation procedure was followed using 12
(418 mg, 0.664 mmol) and 5 (220 mg, 0.731 mmol), with TMSOTf
(24 mL/1 mL of dry DCM, 0.113 mmol), except using 25 mL dry DCM
for both steps. Repeated flash column chromatography resulted in
13 as well as 14, 15, and 16 as purified compounds in few of the
fractions; the percent yield of each product was determined by
comparing the NMR of the crude reaction mixture to their corre-
sponding pure compounds. 13: 1H NMR (CDCl3):
d 7.36e7.29 (m,
10H), 5.41 (d, J¼3.4 Hz, 1H), 4.96e4.87 (m, 3H), 4.82 (d, J¼10.8 Hz,
1H), 4.75e4.70 (m, 2H), 4.60 (d, J¼12.0 Hz, 1H), 4.53 (m, 1H),
4.20e4.15 (m, 2H), 4.11e3.99 (m, 3H), 3.88 (t, J¼9.9 Hz, 1H),
3.63e3.55 (m, 2H), 3.33e3.28 (m, 1H), 2.14 (s, 3H), 2.11 (s, 3H), 2.10
(CDCl3,
a
/
b
ratio is 1.0:0.2):
d
7.45e7.30 (m, 12H), 6.35 (d, J¼3.5 Hz,
1H1a), 5.65 (d, J¼8.2 Hz, 0.2H1b), 4.93 (d, J¼10.7 Hz, 1.2H),
4.77e4.65 (m, 2.4H), 4.62 (d, J¼10.7 Hz, 1.4 H), 4.29 (d, J¼3.2 Hz,
2.4H), 3.96 (m, 2.2H), 3.56 (dd, J¼10.1, 3.5 Hz, 1H), 3.45e3.30 (m,
1.4H), 2.18 (s, 3H), 2.11 (s, 0.6H), 2.09 (s, 0.6H), 2.08 (s, 3H). 13C
(s, 3H), 2.07 (s, 3H). 13C NMR (CDCl3):
d 171.1, 170.7, 170.1, 169.5,
137.4, 137.3, 128.7, 128.6, 128.4, 128.3, 128.2, 127.8, 101.7, 89.6, 74.7,
73.2, 71.9, 70.7, 69.5, 68.4, 68.2, 67.3, 64.0, 62.3, 62.0, 60.6, 20.9,
20.8, 20.8, 20.7. HRFABMS m/z 741.2739 [MþHþ] (calcd for
NMR (DEPT, CDCl3):
d 129.0e128.0 (20C), 93.9, 88.7, 79.0, 76.8,
75.9, 75.2, 75.1, 74.9, 74.3, 73.1, 72.8, 70.8, 65.3, 65.2, 62.8, 62.4,
21.0, 20.9, 20.8, 20.7.
C34H40N6O13, 741.2732). 14: 1H NMR (CDCl3):
d 7.40e7.30 (m, 10H),
5.33 (d, J¼3.5 Hz, 1H), 5.07 (t, J¼10.1 Hz, 1H), 4.95 (d, J¼11.0 Hz, 1H),
4.89e4.86 (m, 1H), 4.84 (d, J¼10.7, 1H), 4.78 (d, J¼11.3 Hz, 1H),
4.60e4.56 (m, 2H), 4.41 (dd, J¼12.3, 1.9 Hz, 1H), 4.26e4.21 (m, 2H),
4.16e4.12 (m,1H), 4.04e3.97 (m, 2H), 3.57 (t, J¼9.8 Hz,1H), 3.54 (m,
1H), 3.30 (dd, J¼9.8, 8.0 Hz, 1H), 3.23 (t, J¼9.7 Hz, 1H), 2.13 (s, 3H),
4.11. 6-O-Acetyl-3-azido-2,4-di-O-benzyl-3-deoxy-
copyranose (11)
a
/
b
-
D
-glu-
1,6-Di-O-acetyl-3-azido-2,4-di-O-benzyl-3-deoxy-
a
/b
-D
-gluco-
pyranose (10) (2.35 g, 5.01 mmol) was deacetylated at the
anomeric position following the general procedure in DMF
(5.0 mL) and CH3COONH4 (0.772 g, 10.02 mmol) stirred for 8 h.
Flash chromatography gave 11 (0.892 g, 96% with respect to re-
covered starting material) as a colorless gum, along with un-
2.09 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H). 13C NMR (CDCl3):
d 170.9,
170.6,169.9,169.2,137.4,137.0,128.8,128.7,128.5,128.3,127.8,127.7,
103.7, 97.9, 79.2, 75.8, 75.1, 74.4, 74.4, 71.2, 68.6, 68.4, 67.9, 62.8,
61.3, 61.2, 21.0, 20.8, 20.7, 20.5. HRFABMS m/z 741.2728 [MþHþ]
(calcd for C34H40N6O13, 741.2732). 15: 1H NMR (CDCl3):
d 7.45e7.30
reacted starting material (1.33 g). 1H NMR (CDCl3,
1.0:0.4):
a
/
b
ratio is
(m, 10H), 5.03 (t, J¼9.8 Hz, 1H), 4.98 (dd, J¼10.1, 7.9 Hz, 1H), 4.93 (d,
J¼10.4 Hz,1H), 4.85 (d, J¼11.0 Hz,1H), 4.78 (d, J¼8.2 Hz,1H), 4.71 (d,
J¼7.6 Hz, 1H), 4.64 (d, J¼11.0 Hz, 1H), 4.56 (d, J¼10.7 Hz, 1H), 4.32
(dd, J¼12.0, 2.2 Hz, 1H), 4.26 (dd, J¼12.3, 4.7 Hz, 1H), 4.18 (dd,
J¼11.7, 4.1 Hz, 1H), 4.10 (dd, J¼12.6, 2.2 Hz, 1H), 4.02e3.92 (m, 1H),
3.69 (t, J¼10.1 Hz, 1H), 3.56 (t, J¼9.5 Hz, 1H), 3.47 (m, 1H), 3.31 (t,
J¼9.5 Hz, 1H), 3.28 (dd, J¼9.8, 7.6 Hz, 1H), 2.13 (s, 3H), 2.11 (s, 3H),
d
7.41 (m, 14H), 5.19 (d, J¼3.5 Hz, 1H1a), 4.97 (d,
J¼11.0 Hz, 0.4H1b), 4.88 (d, J¼10.7 Hz, 1.4H), 4.81 (m, 1.4H), 4.73
(m, 1.4H), 4.59 (d, J¼11 Hz, 1.4H), 4.38 (dd, J¼12.0, 2.2 Hz, 0.4H),
4.29 (dd, J¼12.0, 2.2 Hz, 1H), 4.25 (dd, J¼12.3, 4.1 Hz, 1H), 4.18 (dd,
J¼12.0, 5.0 Hz, 0.4H), 4.10 (m, 1H), 3.96 (t, J¼9.8 Hz, 1H), 3.60 (t,
J¼9.5 Hz, 0.4H), 3.56 (m, 0.4H), 3.42 (dd, J¼10.0, 3.5 Hz, 1H), 3.30
(m, 1.8H), 2.07 (s, 4.2H). 13C NMR (CDCl3):
d
170.8, 170.7, 137.6,
2.06 (s, 3H), 2.03 (s, 3H). 13C NMR (CDCl3):
d 170.8, 170.5, 169.3,
137.2, 137.2, 137.1, 128.8e128.0 (20C), 97.5, 90.3, 80.7, 78.1, 75.9,
75.8, 75.0, 74.9, 74.6, 73.6, 73.2, 68.5, 68.3, 65.1, 62.9, 62.8,
20.9, 20.9.
169.2, 137.5, 137.1, 128.9, 128.7, 128.6, 128.5, 128.4, 128.4, 100.3, 98.0,
79.1, 75.3, 74.9, 74.7, 73.6, 73.0, 71.1, 68.3, 68.1, 64.1, 62.6, 62.0, 20.9,
20.8, 20.7, 20.7. HRFABMS m/z 741.2735 [MþHþ] (calcd for