Arch. Pharm. Chem. Life Sci. 2011, 344, 648–657
Novel D-Glucuronic Acid Acetylated Derivatives
655
(br s, 4H, aromatic H), 6.06 (d, 1H, J1-2 ¼ 8.4 Hz, H-1), 5.53 (apt t,
1H, H-4), 5.26 (apt t, 1H, H-3), 5.08 (apt t, 1H, H-2), 4.46 (d, 1H,
J5-4 ¼ 9.7 Hz, H-5), 2.09, 2.03, 1.97, 1.92 (4s, 12H, 4 COCH3). Anal.
calcd. for C20H22BrNO10 (516.3): C, 46.53; H, 4.29; Br, 15.48; N,
2.71. Found: C, 46.41; H, 4.51; Br, 15.62; N, 2.79.
N-(1H-Benzimidazol-2-yl)-1,2,3,4-tetra-O-acetyl-b-D-
glucopyranuronamide (14)
White solid; (10%); mp 142–1448C; Rf ¼ 0.29 (EtOAc/petroleum
1
ether, 1:1); H-NMR (270 MHz, DMSO-d6): d 7.50 (s, 2H, aromatic
H), 7.23 (s, 2H, aromatic H), 6.09 (d, 1H, J1-2 ¼ 9.7 Hz, H-1), 5.56
(apt t, 1H, H-4), 5.35 (apt t, 1H, H-3), 5.10 (apt t, 1H, H-2),
4.65 (d, 1H, J5-4 ¼ 11.5 Hz, H-5), 2.10, 2.04, 1.98, 1.96 (4s, 12H,
4 COCH3). Anal. calcd. for C21H23N3O10 (477.4): C, 52.83; H, 4.86;
N, 8.80. Found: C, 52.66; H, 5.02; N, 8.65.
N-(2-Chloro-4-nitrophenyl)-1,2,3-tri-O-acetyl-D4,5-b-D-
glucopyranuronamide (9)
Yellow oil; (43%); Rf ¼ 0.85 (EtOAc/petroleum ether, 1:1); 1H-NMR
(500 MHz, CDCl3): d 9.15 (s, 1H, NH), 8.74 (d, 1H, aromatic H),
8.33 (d, 1H, aromatic H), 8.20 (dd, 1H, aromatic H), 6.44 (d, 1H,
J1-2 ¼ 4.6 Hz, H-1), 6.41 (dd, 1H, H-4), 5.32 (m, 1H, H-3), 5.20 (br s,
1H, H-2), 2.15, 2.14, 2.12 (3s, 9H, 3 COCH3). Anal. calcd. for
C18H17ClN2O10 (456.8): C, 47.33; H, 3.75; Cl, 7.76 N, 6.13.
Found: C, 47.50; H, 3.52; Cl, 7.49; N, 6.22.
Ethyl 1,2,3-tri-O-acetyl-D4,5-b-D-glucpyranuronate (16)
Colorless oil; (49%); Rf ¼ 0.29 (EtOAc/petroleum ether, 1:3);
1H-NMR (500 MHz, CDCl3): d 6.41 (d, 1H, J1-2 ¼ 2.3 Hz, H-1),
6.27 (dd, 1H, H-4), 5.23 (m, 1H, H-3), 5.15 (br s, 1H, H-2), 4.31
(q, 2H, CH2), 2.12, 2.11, 2.10 (3s, 9H, 3 COCH3), 1.34 (t, 3H, CH3);
13C-NMR (125 MHz, CDCl3): d 169.7, 169.1, 168.4 (3 COCH3), 161.2
(COOEt), 143.2 (C-5), 106.6 (C-4), 88.5 (C-1), 66.7 (C-2), 63.6 (C-3),
62.0 (OCH2CH3), 20.8, 20.7 (3 COCH3), 14.13 (OCH2CH3). Anal.
calcd. for C14H18O9 (330.3): C, 50.91; H, 5.49. Found: C, 50.76;
H, 5.14.
N-(2-Chloro-4-nitrophenyl)-1,2,3,4-tetra-O-acetyl-b-D-
glucopyranuronamide (10)
White solid; (11%); mp 169–1708C; Rf ¼ 0.25 (EtOAc/petroleum
ether, 1:3); 1H-NMR (500 MHz, CDCl3): d 8.90 (s, 1H, NH), 8.52
(d, 1H, aromatic H), 8.29 (s, 1H, aromatic H), 8.15 (m, 1H, aromatic
H), 5.84 (d, 1H, J1-2 ¼ 7.5 Hz, H-1), 5.35 (m, 2H, H-3 and H-4
overlapping), 5.18 (apt t, 1H, H-2), 4.28 (d, 1H, J5-4 ¼ 9.8 Hz,
H-5), 2.15, 2.10, 2.06, 2.02 (4s, 12H, 4 COCH3). Anal. calcd. for
C20H21ClN2O12 (516.8): C, 46.48; H, 4.10; Cl, 6.86 N, 5.42. Found:
C, 46.59; H, 4.01; Cl, 6.58; N, 5.61.
N-(Pyrazin-2-yl)-1,2,3,4-tetra-O-acetyl-b-D-
glucopyranuronamide (17)
To a solution of 1,2,3,4-tetra-O-acetyl-b-D-glucuronic acetic anhy-
dride (1, 0.5 g, 1.23 mmol) in dry methylene chloride (30 mL)
and under argon, 2-aminopyrazine (0.118 g, 1.23 mmol) was
added and the reaction mixture was stirred overnight at room
temperature. The mixture was then diluted with methylene
chloride, transferred to a separating funnel and washed with
1 M HCl (2 ꢂ 30 mL), saturated NaHCO3 (2 ꢂ 30 mL), deionized
water (2 ꢂ 30 mL), dried over anhydrous Na2SO4 and filtered.
The solvent was then removed and the residue was purified by
column chromatography (EtOAc/petroleum ether, 1:3) to afford
the title compound as a white solid (0.23 mg, 42%); mp 108–
1108C; Rf ¼ 0.37 (EtOAc/petroleum ether, 1:1); 1H-NMR
(270 MHz, CDCl3): d 9.40 (s, 1H, aromatic H), 8.61 (s, 1H, NH),
8.38 (d, 1H, aromatic H), 8.27 (d, 1H, aromatic H), 5.82 (d, 1H,
J1-2 ¼ 8.1 Hz, H-1), 5.32 (m, 2H, H-3 and H-4 overlapping), 5.15
(apt t, 1H, H-2), 4.24 (d, 1H, J5-4 ¼ 8.8 Hz, H-5), 2.15, 2.10, 2.05,
2.02 (4s, 12H, 4 COCH3). Anal. calcd. for C18H21N3O10 (439.3):
C, 49.20; H, 4.82; N, 9.56. Found: C, 49.41; H, 4.77; N, 9.46.
N-(Thiazol-2-yl)-1,2,3-tri-O-acetyl-D4,5-b-D-
glucopyranuronamide (11)
White solid; (43%); mp 103–1048C; Rf ¼ 0.5 (EtOAc/petroleum
ether, 1:1); 1H-NMR (500 MHz, CDCl3): d 7.44 (d, 1H, aromatic
H), 6.98 (d, 1H, aromatic H), 6.34–6.32 (m, 2H, H-1 and H-4
overlapping), 5.22 (m, 1H, H-3), 5.12 (br s, 1H, H-2), 2.05, 2.04,
2.01 (3s, 9H, 3 COCH3); 13C-NMR (50 MHz, CDCl3): d 170.0, 169.5,
168.8 (3 COCH3), 158.1 (aromatic C), 157.5 (CONH), 143.6 (C-5),
138.4 (aromatic C), 115.0 (aromatic C), 106.1 (C-4), 88.8 (C-1), 67.3
(C-2), 63.8 (C-3), 21.2, 21.1 (3 COCH3). Anal. calcd. for C15H16N2O8S
(384.3): C, 46.87; H, 4.20; N, 7.29; S, 8.34. Found: C, 46.68; H, 4.12;
N, 7.14; S, 8.56.
N-(Thiazol-2-yl)-1,2,3,4-tetra-O-acetyl-b-D-
glucopyranuronamide (12)
N-(Pyrazin-2-yl)-1,2,3-tri-O-acetyl-D4,5-b-D-
glucopyranuronamide (15)
White solid; (10%); mp 178–1808C; Rf ¼ 0.37 (EtOAc/petroleum
ether, 1:1); 1H-NMR (270 MHz, DMSO-d6): d 12.49 (s, 1H, NH), 7.50
(d, 1H, aromatic H), 7.31 (d, 1H, aromatic H), 6.08 (d, 1H,
J1-2 ¼ 8.1 Hz, H-1), 5.55 (apt t, 1H, H-4), 5.34 (apt t, 1H, H-3),
5.12 (apt t, 1H, H-2), 4.61 (d, 1H, J5-4 ¼ 8.9 Hz, H-5), 2.08, 2.03,
DBU (0.05 mL, 0.33 mmol) was added to a stirred solution of
N-(pyrazin-2-yl)-1,2,3,4-tetra-O-acetyl-b-D-glucopyranuronamide (9,
0.1 g, 0.23 mmol) in dry methylene chloride (5 mL) cooled to
08C. After stirring for 30 min at 08C, the solvent was removed
in vacuo and the dark brown residue was purified by column
chromatography (EtOAc/petroleum ether, 1:3) to afford the title
compound as a colorless oil (73 mg, 81%); Rf ¼ 0.38 (EtOAc/
petroleum ether, 1:1); 1H-NMR (500 MHz, CDCl3): d 9.51 (s, 1H,
aromatic H), 8.77 (s,1H, NH), 8.33 (d, 1H, aromatic H), 8.25 (s, 1H,
aromatic H), 6.36 (m, 2H, H-1 and H-4 overlapping), 5.26 (m, 1H,
H-3), 5.14 (br s, 1H, H-2), 2.09, 2.07, 2.05 (3s, 9H, 3 COCH3); 13C-NMR
(50 MHz, CDCl3): d 169.5, 169.1, 168.5 (3 COCH3), 158.2 (CONH),
147.2 (aromatic C), 143.6 (C-5), 142.3 (aromatic CH), 140.8 (aromatic
CH), 137.1 (aromatic CH), 105.2 (C-4), 88.3 (C-1), 66.8 (C-2), 63.3 (C-3),
20.7, 20.6 (3 COCH3). Anal. calcd. for C16H17N3O8 (379.3): C, 50.66;
H, 4.52; N, 11.08. Found: C, 50.39; H, 4.75; N, 10.96.
1.97, 1.93 (4s, 12H, 4 COCH3). Anal. calcd. for C17H20N2O10
S
(444.4): C, 45.94; H, 4.54; N, 6.30; S, 7.22. Found: C, 45.70; H,
4.81; N, 6.58; S, 6.98.
N-(1H-Benzimidazol-2-yl)-1,2,3-tri-O-acetyl-D4,5-b-D-
glucopyranuronamide (13)
Yellow oil; (39%); Rf ¼ 0.35 (EtOAc/petroleum ether, 1:1); 1H-NMR
(500 MHz, CDCl3): d 7.42 (m, 2H, aromatic H), 7.15 (m, 2H,
aromatic H), 6.35 (d, 1H, J1-2 ¼ 4.6 Hz, H-1), 6.27 (d, 1H, H-4),
5.23 (m, 1H, H-3), 5.12 (br s, 1H, H-2), 2.06, 2.02, 2.00 (3s, 9H,
3 COCH3). Anal. calcd. for C19H19N3O8 (417.3): C, 54.68; H, 4.49;
N, 10.07. Found: C, 54.78; H, 4.41; N, 9.96.
ß 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.archpharm.com