Q. Zhao et al. / Carbohydrate Research 343 (2008) 2459–2462
2461
recorded on a Finnigan MAT-95/711spectrometer. High-resolution
mass spectra (HRMS) were recorded on an FTMS spectrometer. Ele-
mental analyses were performed on a Carlo Erba 1106 analyzer.
(400 MHz, CDCl3): d 8.94, 23.39, 25.21, 26.41, 27.43, 49.81, 52.46,
56.73, 65.52, 68.77, 74.72, 75.27, 107.48, 108.86, 145.01, 161.57,
170.82, 174.27; HRESIMS: calcd for
C
18H26N4O8Na [M+Na]+:
449.1648; found: m/z 449.1636. Anal. Calcd for C18H26N4O8: C,
1.2. Preparation of methyl 5-acetamido-2,6-anhydro-4-azido-
50.70; H, 6.15; N, 13.14. Found: C, 50.71; H, 6.19; N, 12.88.
3,4,5-trideoxy-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-
enonic acid (3)13
1.3.2. Methyl 5-acetamido-2,6-anhydro-4-azido-3,4,5-trideoxy-
7-O-n-butyryl-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-
enonic acid (4b)
Methyl 5-acetamido-2,6-anhydro-4-azido-3,4,5-trideoxy-
D-gly-
cero- -galacto-non-2-enonic acid 2 (724 g, 2.7 mmol) was dis-
D
The residue was chromatographed on silica gel with 3:7 EtOAc–
solved in acetone (360 mL), and Dowex 50W ꢀ 8X (H+) resin
(10 g) was added to the resulting soln while stirring at room tem-
perature to adjust pH to 4. The mixture was then stirred for 3 h.
Then, the soln was filtered and evaporated to give an oil, then sat-
urated aq sodium hydrogen carbonate (100 mL) and CH2Cl2
(200 mL) were added. After separation, the aq layer was extracted
with CH2Cl2 (3 ꢀ 100 mL). All organic layers were combined,
washed with brine (200 mL), dried over anhyd sodium sulfate,
and the solvent was removed by distillation under diminished
pressure to give a white solid, which was of sufficient quality for
use in the next step. An analytically pure sample was obtained
via silica gel column chromatography (1:2 hexane–EtOAc). Yield:
petroleum ether to give compound 4b (114 mg, 96%); white solid;
½
a 2D0
+41.6 (c 0.65, MeOH); mp 126–128 °C; Rf 0.41 (1:1 EtOAc–
ꢁ
petroleum ether); d 5.95 (d, 1H, J 7.9 Hz, NH), 5.94 (d, 1H, J
2.8 Hz, 3-H), 5.36 (dd, 1H, J 1.7, 5.1 Hz, 7-H), 4.71 (dd, 1H, J 2.7,
9.1 Hz, 4-H), 4.65 (dd, 1H, J 2.0, 10.4 Hz, 6-H), 4.37 (dd, 1H, J 6.1,
11.5 Hz, 8-H), 4.13 (dd, 1H, J 6.4, 9.0 Hz, 9-Ha), 3.93 (dd, 1H, J
6.2, 9.0 Hz, 9-Hb), 3.80 (s, 3H, CO2Me), 3.52 (dd, 1H, J 8.7, 17.4,
18.7 Hz, 5-H), 2.37 (m, 2H, CH2), 2.00 (s, 3H, NAc), 1.65 (m, 2H,
CH2), 1.35 (s, 3H, CH3), 1.33 (s, 3H, CH3), 0.95 (s, 3H, J 7.2 Hz,
CH3); 13C NMR (400 MHz, CDCl3): d 13.66, 18.25, 23.45, 25.25,
26.50, 35.99, 49.80, 52.53, 56.84, 65.61, 68.73, 74.75, 75.37,
107.55, 108.93, 145.07, 161.65, 170.93, 173.47; HRESIMS: calcd
for C19H28N4O8Na [M+Na]+: 463.1805; found: m/z 463.1804. Anal.
Calcd for C19H28N4O8: C, 51.81; H, 6.41; N, 12.72. Found: C,
51.92; H, 6.34; N, 12.57.
21.5 g (80%); ½a 2D0
ꢁ
+158 (c 0.42, CHCl3), lit.13 +161; mp 95–97 °C;
Rf 0.55 (20:1 CH2Cl2–MeOH); 1H NMR (300 MHz, CDCl3): d 5.95
(d, 1H, J 2.5 Hz, H-3), 5.85 (d, 1H, J 8.0 Hz, NH), 5.35 (dd, 1H, J
2.0, 5.3 Hz, H-7), 4.67 (dd, 1H, J 2.5, 9.0 Hz, H-4), 4.64 (dd, 1H, J
1.9, 11.2 Hz, H-6), 4.38 (dd, 1H, J 6.1, 11.7 Hz, H-8), 4.14 (dd, 1H,
J 6.2, 9.0 Hz, H-9), 3.96 (dd, 1H, J 6.1, 8.8 Hz, H-9), 3.81 (s, 3H,
CO2Me), 3.60 (dd, 1H, J 8.7, 18.6 Hz, H-5), 2.14 (s, 3H, OAc), 2.01
(s, 3H, NAc), 1.37 (s, 3H, CH3), 1.35 (s, 3H, CH3); 13C NMR
(400 MHz, CDCl3): d 20.73, 20.85, 23.30, 48.67, 52.58, 57.56,
61.96, 67.73, 70.82, 75.69, 107.50, 145.15, 161.50, 170.42,
170.64; HRESIMS: calcd for C15H22N4O7Na [M+Na]+: 393.1386;
found: m/z 393.1397.
1.3.3. Methyl 5-acetamido-2,6-anhydro-4-azido-3,4,5-trideoxy-
8,9-O-isopropylidene-7-O-methoxylacetyl-D-glycero-D-galacto-
non-2-enonic acid (4c)
The residue was chromatographed on silica gel with EtOAc
(60%) in petroleum ether to give compound 4c (116 mg, 97%);
white solid; ½a 2D0
ꢁ
+42.0 (c 0.23, MeOH); mp 80–81 °C; Rf 0.15 (1:1
EtOAc–petroleum ether); 1H NMR (400 MHz, CDCl3): d 6.50 (d,
1H, J 8.5 Hz, NH), 5.92 (d, 1H, J 2.4 Hz, 3-H), 5.48 (dd, 1H, J
1.5, Hz, 7-H), 4.60 (dd, 1H, J 1.5, 10.5 Hz, 6-H), 4.56 (dd, 1H, J 2.6,
9.5 Hz, 4-H), 4.36 (dd, 1H, J 5.9, 10.7 Hz, 8-H), 4.19 (d, 1H, J
16.8 Hz, CH–H), 4.13 (dd, 1H, J 6.4, 9.1 Hz, 9-Ha), 4.02 (d, 1H, J
16.8 Hz, CH–H), 3.95 (dd, 1H, J 6.2, 9.1 Hz, 9-Hb), 3.78 (s, 3H,
CO2Me), 3.70 (dd, 1H, J 9.2, 19.0 Hz, 5-H), 3.45 (s, 3H, OCH3), 1.99
(s, 3H, NAc), 1.32 (s, 3H, CH3), 1.31 (s, 3H, CH3); 13C NMR
(400 MHz, CDCl3): d 23.30, 25.09, 26.42, 49.69, 52.48, 56.81,
59.40, 65.40, 69.36 (2C), 74.67, 75.23, 107.65, 108.85, 144.99,
1.3. General procedure for the preparation of methyl 5-
acetamido-7-O-acyl-2,6-anhydro-4-azido-3,4,5-trideoxy-8,9-O-
isopropylidene-D-glycero-D-galacto-non-2-enonic acid (4a–e)
A suspension of methyl 5-acetamido-2,6-anhydro-4-azido-3,4,
5-trideoxy-8,9-O-isopropylidene- -glycero- -galacto-non-2-enonic
D
D
acid 3 (100 mg, 0.27 mmol) in pyridine (1.0 mL) was treated with
DMAP (4 mg). The resulting mixture was cooled in an ice-water
bath while propionic anhydride, butyric anhydride, methoxyacetic
anhydride, benzoic anhydride, or acetic anhydride (0.54 mmol)
was added dropwise, respectively. After stirring for 10–24 h at
room temperature the mixture was concentrated to give an oil
which was dissolved in EtOAc (6 mL) and washed sequentially
with 1 M hydrochloric acid (2 ꢀ 3 mL), saturated aq sodium hydro-
gen carbonate (3 ꢀ 3 mL), and finally brine (3 mL). The organic
layer was then dried over MgSO4, concentrated, and the residues
were purified by column chromatography or recrystallization.
161.49, 170.25, 170.99; HRESIMS: calcd for
[M+Na]+: 465.1597; found: m/z 465.1579. Anal. Calcd for
18H26N4O9: C, 48.87; H, 5.92; N, 12.66. Found: C, 48.89; H, 5.95;
C18H26N4O9Na
C
N, 12.49.
1.3.4. Methyl 5-acetamido-2,6-anhydro-4-azido-7-O-benzoyl-
3,4,5-trideoxy-8,9-O-isopropylidene-D-glycero-D-galacto-non-2-
enonic acid (4d)
The residue was chromatographed on silica gel with 2:3 EtOAc–
petroleum ether to give 4d (126 mg, 98%); white solid; ½a D20
ꢁ
+51.0
(c 0.24, MeOH); mp 166–167 °C; Rf 0.37 (1:1 EtOAc–petroleum
ether); 1H NMR (400 MHz, CDCl3): d 8.06 (d, 2H, J 7.2 Hz, 2-H
and 20-H), 7.61 (t, 1H, J 7.5 Hz, 40-H), 7.47 (d, 1H, J 7.4 Hz, 3-H
and 30-H), 6.04 (d, 1H, J 7.1 Hz, NH), 5.94 (d, 1H, J 2.7 Hz, 3-H),
5.62 (d, 1H, J 1.6, 4.7 Hz, 7-H), 5.08 (dd, 1H, J 2.7, 9.3 Hz, 4-H),
5.00 (dd, 1H, J 1.5, 10.3 Hz, 6-H), 4.51 (dd, 1H, J 6.0, 11.0 Hz,
8-H), 4.23 (dd, 1H, J 6.2, 9.1 Hz, 9-Ha), 4.16 (dd, 1H, J 6.1, 8.9 Hz,
9-Hb), 3.82 (s, 3H, CO2Me), 3.20 (ddd, 1H, J 7.3, 9.6, 17.1 Hz,
5-H), 2.06 (s, 3H, NAc), 1.34 (s, 3H, CH3), 1.25 (s, 3H, CH3); 13C
NMR (400 MHz, CDCl3): d 23.57, 25.28, 26.47, 51.78, 52.49, 55.80,
65.62, 69.93, 74.89, 75.29, 107.70, 109.04, 128.64 (2C), 129.03,
130.01 (2C), 133.74, 145.05, 161.66, 166.37, 171.34; HRESIMS:
1.3.1. Methyl 5-acetamido-2,6-anhydro-4-azido-3,4,5-trideoxy-
8,9-O-isopropylidene-7-O-propionyl-D-glycero-D-galacto-non-2-
enonic acid (4a)
The residue was chromatographed on silica gel with 1:1 EtOAc–
petroleum ether to give 4a (111 mg, 96%); white solid; ½a D20
ꢁ
+48.1
(c 0.48, MeOH); mp 63–64 °C; Rf 0.28 (1:1 EtOAc–petroleum
ether); 1H NMR (400 MHz, CDCl3): d 5.95 (d, 1H, J 2.6 Hz, 3-H),
5.85 (d, 1H, J 7.7 Hz, NH), 5.37 (dd, 1H, J 1.9, 5.2 Hz, 7-H), 4.72
(dd, 1H, J 2.7, 9.1 Hz, 4-H), 4.66 (dd, 1H, J 1.8, 10.6 Hz, 6-H), 4.37
(dd, 1H, J 6.2, 11.6 Hz, 8-H), 4.14 (dd, 1H, J 6.1, 9.0 Hz, 9-Ha),
3.95 (dd, 1H, J 6.3, 9.0 Hz, 9-Hb), 3.80 (s, 3H, CO2Me), 3.53 (dd,
1H, J 8.7, 18.5 Hz, 5-H), 2.43 (m, 2H, CH2), 2.01 (s, 3H, NAc), 1.36
(s, 3H, CH3), 1.34 (s, 3H, CH3), 1.16 (t, 3H, J 7.6 Hz, CH3); 13C NMR
calcd for
C
22H26N4O8Na [M+Na]+: 497.1648; found: m/z