M. Zhong et al. / Carbohydrate Research 345 (2010) 1099–1106
1103
CDCl3): d 144.87 (C-1), 99.83 (C-2), 76.48, 76.06, 71.03, 59.26,
58.76, 55.81. HRMS: m/z Calcd for C8H13N3O3Na [M+Na]+,
222.0849. Found 222.0841.
in a water bath, and then NaClO2 (569 mg, 6.33 mmol) was added.
O2 evolved from the solution, and a deep-yellow mixture was ob-
tained. The mixture was stirred for 2 h, and then complete con-
sumption of the starting product was observed by TLC. On
completion of the reaction, the mixture was diluted with water
(50 mL), acidified with 10% aq HCl, and extracted with CH2Cl2
(5 Â 50 mL). The combined organic layer was washed with water
and dried (MgSO4). The pure compound, 8a (396 mg, 95% yield)
or 8b (388 mg, 93% yield), was isolated as a colorless syrup by re-
3.4. 2,6-Anhydro-3-azido-1,4-di-O-benzyl-3,5-dideoxy-5-C-
formyl-D-arabino-hex-5-enitol (6a) and 1,5-anhydro-4-azido-
3,6-di-O-benzyl-2,4-dideoxy-2-C-formyl-D-arabino-hex-1-enitol
(6b)
To a solution of 4a or 4b (1.0 g, 2.85 mmol) in DMF (10 mL) was
added POCl3 (1.49 mL, 14.2 mmol) slowly at 0 °C. The mixture was
stirred at room temperature for 10 h then poured into satd aq NaH-
CO3 (50 mL). The mixture was stirred for 10 h and then extracted
with CH2Cl2 (3 Â 50 mL). The combined organic layer was dried
(MgSO4), filtered, concentrated to dryness, and then purified by sil-
ica gel column chromatography (6:1 petroleum ether–EtOAc) to
give 6a (767 mg, 71% yield) or 6b (475 mg, 44% yield) as a colorless
moval of solvent. Compound 8a: [a]
+14 (c 1.4, CHCl3). 1H NMR
D
(300 MHz, CDCl3): d 7.63 (s, 1H, H-1), 7.35–7.29 (m, 10H, Ph),
4.83–4.73 (m, 2H, PhCH2), 4.59 (d, 1H, J 3.9 Hz, H-3), 4.58–4.48
(m, 2H, PhCH2), 4.38–4.36 (m, 1H, H-5), 3.95 (t, 1H, H-4), 3.86–
3.73 (m, 2H, H-6); 13C NMR (75 MHz, CDCl3): d 171.50 (COOH),
157.36 (C-1), 137.65–127.88 (Ph), 106.47 (C-2), 76.58, 73.72,
73.61, 69.09, 67.98, 57.02. HRMS: m/z Calcd for C21H21N3O5Na
[M+Na]+, 418.1373. Found 418.1376. Compound 8b: [
a]
À8.0 (c
D
syrup. Compound 6a: [
a]
D
+51 (c 1.1, CHCl3). 1H NMR (300 MHz,
1.0 CHCl3). 1H NMR (400 MHz, CDCl3): d 7.74 (s, 1H, H-1), 7.36–
7.28 (m, 10H, Ph), 4.79–4.67 (m, 2H, PhCH2), 4.51–4.50 (m, 3H,
H-3 and PhCH2), 4.33–4.30 (m, 1H, H-5), 3.98 (d, 1H, J 2.8 Hz, H-
4), 3.79–3.73 (m, 2H, H-6); 13C NMR (100 MHz, CDCl3): d 172.20
(COOH), 158.04 (C-1), 138.30–128.51 (Ph), 107.07 (C-2), 77.13,
74.26, 74.15, 68.92, 68.51, 57.53. HRMS: m/z Calcd for C21H21N3O5-
Na [M+Na]+, 418.1373. Found 418.1370.
CDCl3): d 9.34 (s, 1H, CHO), 7.35–7.28 (m, 10H, Ph), 7.24 (s, 1H, H-
1), 4.85–4.73 (m, 2H, PhCH2), 4.61 (d, 1H, J 4.2 Hz, H-3), 4.58–4.48
(m, 2H, PhCH2), 4.36–4.34 (m, 1H, H-5), 3.89 (t, 1H, H-4), 3.85–
3.73 (m, 2H, H-6); 13C NMR (75 MHz, CDCl3): d 189.09 (CHO),
163.54, 163.50 (C-1), 137.77–127.85 (Ph), 119.04 (C-2), 77.45,
73.53, 73.49, 67.95, 67.69, 56.54. HRMS: m/z Calcd for C21H21N3O4Na
[M+Na]+, 402.1424. Found 402.1431. Compound 6b: [
a
]D +23 (c 1.6
Compounds 9a and 9b were also prepared by the same proce-
dure as described above and their spectral and analytical data
are given below.
CHCl3). 1H NMR (400 MHz, CDCl3): d 9.39 (s, 1H, CHO), 7.35–7.25
(m, 10H, Ph), 7.22 (s, 1H, H-1), 4.81–4.66 (m, 2H, PhCH2), 4.55–
4.51 (m, 3H, PhCH2 and H-3), 4.37–4.36 (m, 1H, H-5), 4.40–3.99
(m, 1H, H-4), 3.83–3.69 (m, 2H, H-6); 13C NMR (100 MHz, CDCl3): d
189.70 (CHO), 163.82 (C-1), 137.78–127.94 (Ph), 117.98 (C-2),
78.29, 73.53, 73.32, 68.10, 67.53, 56.61. HRMS: m/z Calcd for
C21H21N3O4Na [M+Na]+, 402.1424. Found 402.1416.
3.7. 2,6-Anhydro-3-azido-5-carboxy-3,5-dideoxy-1,4-di-O-meth-
yl-D-arabino-hex-5-enitol (9a) and 1,5-anhydro-4-azido-2-carb-
oxy-2,4-dideoxy-3,6-di-O-methyl-D-arabino-hex-1-enitol (9b)
The other compounds (7a and 7b) were also prepared by the
same procedure as described above, and their spectral and analyt-
ical data are given below.
Compound 9a (95% yield) or 9b (92% yield) was obtained as a
colorless syrup. Compound 9a: [
+32 (c 1.0, CHCl3). 1H NMR
a
]
D
(400 MHz, CDCl3): d 7.59 (s, 1H, H-1), 4.35–4.32 (m, 2H, H-5,
H-3), 3.98 (t, 1H, J 4.0, 4.0 Hz, H-4), 3.71 (dd, 1H, J 7.6, 11.2 Hz,
H-6a), 3.65 (dd, 1H, J 3.6 Hz, H-6b), 3.55 (s, 3H, CH3), 3.39 (s, 3H,
CH3); 13C NMR (100 MHz, CDCl3): d 171.36 (COOH), 157.07 (C-1),
106.24 (C-2), 76.38, 70.53, 70.18, 59.15, 59.00, 56.54. HRMS: m/z
Calcd for C9H13N3O5Na [M+Na]+, 266.0747. Found 266.0746. Com-
3.5. 2,6-Anhydro-3-azido-3,5-dideoxy-5-C-formyl-1,4-di-O-
methyl-D-arabino-hex-5-enitol (7a) and 1,5-anhydro-4-azido-
2,4-dideoxy-2-C-formyl-3,6-di-O-methyl-D-arabino-hex-1-
enitol (7b)
pound 9b: [a]
D +29 (c 1.5, CHCl3). 1H NMR (400 MHz, CDCl3): d 7.71
Compound 7a (68% yield) or 7b (42% yield) was obtained as a
colorless syrup. Compound 7a: [
+75 (c 1.5, CHCl3). 1H NMR
(s, 1H, H-1), 4.49–4.46 (m, 1H, H-5), 4.06 (s, 1H, H-3), 4.00 (t, 1H,
J 3.2 Hz, H-4), 3.72 (dd, 1H, J 6.8, 10.4 Hz, H-6a), 3.62 (dd, 1H,
J 4.8 Hz, H-6b), 3.51 (s, 3H, CH3), 3.41 (s, 3H, CH3); 13C NMR
(100 MHz, CDCl3): d 171.96 (COOH), 157.13 (C-1), 104.89 (C-2),
76.70, 70.65, 70.33, 59.12, 57.78, 55.49. HRMS: m/z Calcd for
C9H13N3O5Na [M+Na]+, 266.0747. Found 266.0746.
a]
D
(300 MHz, CDCl3): d 9.37 (s, 1H, CHO), 7.30 (s, 1H, H-1), 4.45–
4.38 (m, 2H, H-5, H-3), 4.01 (t, 1H, J 4.2, 3.6 Hz, H-4), 3.79–3.66
(m, 2H, H-6), 3.57 (s, 3H, CH3), 3.42 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3): d 188.92 (CHO), 163.42 (C-1), 118.74 (C-2),
77.62, 70.34, 69.09, 59.26, 59.15, 56.26. HRMS: m/z Calcd for
C9H13N3O4Na [M+Na]+, 250.0798. Found 250.0801. Compound
3.8. 3-Amino-2,6-anhydro-1,4-di-O-benzyl-5-carboxy-3,5-
dideoxy-D-arabino-hex-5-enitol hydrochloride (10a) and 4-
7b: [a
]
D
+32 (c 1.5, CHCl3). 1H NMR (400 MHz, CDCl3): d 9.38 (s,
1H, CHO), 7.36 (s, 1H, H-1), 4.51–4.47 (m, 1H, H-5), 4.12 (dd, 1H,
J 1.2, 3.6 Hz, H-3), 3.40 (t, 1H, H-4), 3.72 (dd, 1H, J 6.8, 10.8 Hz,
H-6a), 3.61 (dd, 1H, J 4.4 Hz, H-6b), 3.51 (s, 3H, CH3), 3.40 (s, 3H,
CH3). 13C NMR (100 MHz, CDCl3): d 189.29 (CHO), 163.51 (C-1),
117.57 (C-2), 78.15, 70.41, 69.05, 59.05, 58.14, 55.75. HRMS: m/z
Calcd for C9H13N3O4Na [M+Na]+, 250.0798. Found 250.0794.
amino-1,5-anhydro-3,6-di-O-benzyl-2-carboxy-2,4-dideoxy-
arabino-hex-1-enitol hydrochloride (10b)
D-
To a stirred solution of 8a or 8b (50 mg, 0.126 mmol) in 10:1
THF–H2O (3 mL) at 60 °C was added Ph3P (100 mg, 0.379 mmol).
After 3 h, the reaction mixture was cooled to room temperature,
and 1 M HCl (0.126 mL) was added. The mixture was concentrated
to dryness, diluted with water (20 mL), and washed with EtOAc
(3 Â 20 mL). The water layer was evaporated under reduced pres-
sure to give 10a (44 mg, 85% yield) or 10b (42 mg, 82% yield) as
3.6. 2,6-Anhydro-3-azido-1,4-di-O-benzyl-5-carboxy-3,5-
dideoxy-D-arabino-hex-5-enitol (8a) and 1,5-anhydro-4-azido-
3,6-di-O-benzyl-2-carboxy-2,4-dideoxy-D-arabino-hex-1-enitol
(8b)
a pale-yellow syrup. Compound 10a: [
a
]
À51 (c 1.5, MeOH). 1H
D
NMR (300 MHz, DMSO-d6): d 7.49 (s, 1H, H-1), 7.37–7.26 (m,
10H, Ph), 4.73–4.48 (m, 4H, 2 Â PhCH2), 4.37–4.35 (m, 1H, H-5),
4.22 (d, 1H, J 4.4 Hz, H-3), 3.47–3.40 (m, 2H, H-6), 3.20–3.19
(m, 1H, H-4); 13C NMR (75 MHz, MeOH-d4): d 167.91 (COOH),
154.63 (C-1), 139.08–127.05 (Ph), 108.03 (C-2), 78.19, 72.82,
To a solution of 6a or 6b (400 mg, 1.05 mmol) in 5 mL of a
mixed solution of 2:2:1 MeCN–tBuOH–H2O were cautiously added
NaH2PO4Á2H2O (0.493 g, 3.16 mmol) and 35% aq H2O2 (161
lL,
5.27 mmol). The resulting mixture was stirred for a few minutes