4198
Q. Zhang et al. / Tetrahedron 68 (2012) 4194e4201
(ESIþ) 505 [MþNa]þ, HRESIMSþ 505.1328, C22H26NaO12 requires
169.6, 169.6, 168.9, 166.7, 165.4, 151.8, 139.8, 129.0, 126.0, 125.0,
114.7, 98.3, 72.9, 71.8, 70.3, 69.2, 61.3, 53.3, 20.8, 20.7, 20.6, 20.5,
14.4; Compound 9f: dH (400 MHz, CDCl3) 7.78 (dd, 1H, J 8.3, 1.9 Hz,
H-4), 7.72 (d, 1H, J 2.1 Hz, H-6), 7.11 (d, 1H, J 8.3 Hz, H-3),
5.38e5.32 (m, overlapping signals, 3H, Glu H-2, H-3, H-4),
5.26e5.21 (m, 1H, overlapping, Glu H-1), 4.37 (q, 2H, J 7.2 Hz,
CH2CH3), 4.29e4.23 (m, 1H, Glu H-5), 3.76 (s, 3H, CO2CH3), 2.29 (s,
3H, 3-OAc), 2.08, 2.06, 2.05 (3ꢂ s, 3ꢂ 3H, overlapping of two
isomers, 3ꢂ Glu OAc), 1.38 (t, 3H, J 7.2 Hz, CH2CH3); dC (100.6 MHz,
CDCl3) 170.1, 169.8, 169.5, 168.6, 166.8, 165.5, 148.1, 144.1, 129.5,
125.2, 123.5, 116.7, 98.7, 72.8, 71.9, 70.5, 69.3, 61.4, 53.2, 20.8e20.5
(4ꢂ OAc overlapping with that of 9e), 14.4; HRESIþ 563.1369;
C24H28NaO14 requires 563.1377.
505.1322.
3.3.6. Methyl-(4-ethoxycarbonyl-2-methoxyphenyl-2,3,4-tri-O-ace-
tyl-b-D-glucopyranoside)uronate (9b). Compound 9b was prepared
in the same way as 9a from 4-hydroxy-3-methoxybenzoate 4b
(1.00 g, 5.10 mmol) as an off-white solid (2.18 g, 83%); mp
128e130 ꢁC; ½a 2D0
ꢃ
ꢀ52.8 (c 1.0, CHCl3), nmax (KBr disc, cmꢀ1) 1758
(C]O), 1712 (C]O); dH (400 MHz, CDCl3) 7.61 (dd, 1H, J 8.4, 2.0 Hz,
H-5), 7.56 (d, 1H, J 1.9 Hz, H-3), 7.13 (d, 1H, J 8.4 Hz, H-6), 5.36e5.27
(m, overlapping signals, 3H, Glu H-2, H-3, H-4), 5.13 (d, 1H, J 7.0 Hz,
Glu H-1), 4.34 (q, 2H, J 7.1 Hz, CH2CH3), 4.14 (m,1H, J 9.5 Hz, Glu H-5),
3.86 (s, 3H, 3-OCH3), 3.72 (s, 3H, CO2CH3), 2.06, 2.04, 2.03 (3ꢂ s, 3ꢂ
3H, 3ꢂ OAc),1.37 (t, 3H, J 7.1 Hz, CH2CH3); dC (100 MHz, CDCl3) 170.2,
169.5, 169.4, 167.0, 166.2, 150.3, 149.6, 126.9, 123.1, 119.1, 113.7, 100.1,
72.8, 71.8, 71.1, 69.3, 61.2, 56.3, 53.1, 20.8, 20.7, 20.6, 14.5; m/z (ESþ)
535 [MþNa]þ, HRESIMSþ 513.1414, C23H28NaO13 requires 535.1428.
3.3.10. 4-Carboxyphenyl-b-D-glucopyranosiduronic acid (1a). A
KOH solution (0.506 g, 9.00 mmol dissolved in 10 mL of H2O) was
added to an ice-cooled solution of 9a (0.483 g, 1.00 mmol) in MeOH
(10 mL). The mixture was stirred at 0e4 ꢁC for 3 days and then
neutralised with Dowex 50WX4-400 ion-exchange resin to pH 7 to
give the bispotassium salt. Purification of the salt by recrystallisa-
tion from H2O and MeOH gave pure dipotassium salt (0.201 g, 51%).
The salt (0.180 g) was then dissolved in water and further acidified
to pH 2e3 with Hþ ion-exchange resin. After removal of solvent, the
free acid of 1a was obtained as white solid (0.140 g, 97%).
3.3.7. Methyl-(5-ethoxycarbonylphenyl-2-methoxy-2,3,4-tri-O-ace-
tyl-b-D-glucopyranoside)urinate (9c). Compound 9c was prepared in
the same way as 9a from 3-hydroxy-4-methoxybenzoate (4c,ꢁ0.688 g,
a 20
3.15 mmol) as an off-white solid (1.20 g, 75%); mp 123e124 C; ½ ꢃD
ꢀ32.5(c 1.0, CHCl3);nmax (KBrdisc, cmꢀ1) 1746(C]O),1711 (C]O); dH
(400 MHz, CDCl3) 7.83 (dd,1H, J 8.4, 2.0 Hz, H-4), 7.80 (d, 1H, J 2.0 Hz,
H-6), 6.92 (d,1H, J 8.4 Hz, H-3), 5.4e5.29 (m, overlapping signals, 3H,
Glu H-2, H-3, H-4), 5.11 (d, 1H, J 7.1 Hz, Glu H-1), 4.35 (q, 2H, J 7.2 Hz,
CH2CH3), 4.14 (m, 1H, J 9.2 Hz, Glu H-5), 3.89 (s, 3H, 3-OCH3), 3.76 (s,
3H, CO2CH3), 2.09, 2.06, 2.05 (3ꢂ s, 3ꢂ 3H, 3ꢂ OAc),1.38 (t, 3H, J 7.2 Hz
CH2CH3); dC (100.6 MHz, CDCl3) 170.3,169.5,169.4,167.0,166.0,154.7,
145.3, 127.2, 123.3, 121.3, 111.7, 100.6, 72.8, 72.0, 71.3, 69.3, 61.0, 56.2,
53.0, 20.8 (two overlapping), 20.7, 14.5; m/z (ESIþ) 535 [MþNa]þ,
HRESIþ 535.1422, C23H28NaO13 requires 535.1428.
Compound 1a (dipotassium salt). White solid. Mp>274 ꢁC (dec);
½
a 2D0
ꢃ
ꢀ80.4 (c 0.25, H2O); nmax (KBr disc, cmꢀ1) 3423 (OH), 1610 (C]
O); dH (400 MHz, MeOD) 7.91 (d, 2H, J 8.9 Hz, H-3 and H-5), 7.08 (d,
2H, J 8.8 Hz, H-2 and H-6), 4.99 (m, 1H, J 7.5 Hz, Glu-H-1), 3.79 (m,
1H, J 9.3 Hz, Glu H-3), 3.54e3.51 (m, 3H, Glu H-2, H-4 and H-5); dC
(100.6 MHz, MeOD) 176.5, 175.2, 161.0, 133.3, 132.1, 116.8, 102.2,
77.9, 76.8, 74.8, 73.8; m/z (ESIꢀ) 351 [MꢀK]ꢀ, HRESIꢀ 351.0115,
C13H12KO9 requires 351.0118.
Compound 1a. White solid. Mp>188 ꢁC (dec); ½a D20
ꢀ77.5 (c 0.2,
ꢃ
3.3.8. Methyl-(5-ethoxycarbonylphenyl-2-benzyloxy-2,3,4-tri-O-ace-
tyl-b-D-glucopyranoside)urinate (9d). Compound 9d was prepared
H2O); nmax (KBr disc, cmꢀ1) 3448 (OH), 3244 (br COOH), 1723 (C]
O); dH (400 MHz, MeOD) 7.98 (d, 2H, J 8.9 Hz, H-3 and H-5), 7.14 (d,
2H, J 8.9 Hz, H-2 and H-6), 5.10 (m, 1H, J 7.5 Hz, Glu-H-1), 4.04 (d,
1H, J 9.7 Hz, Glu H-3), 3.65e3.60 (m, 1H, Glu H-4), 3.56e3.50 (m,
2H, H-2 and H-5); dC (100 MHz, MeOD) 172.5, 169.7, 162.7, 132.8,
126.0, 117.3, 101.7, 77.4, 76.7, 74.6, 73.1; m/z (ESIꢀ) 313 [MꢀH]ꢀ,
HRESIꢀ 313.0550, C13H13O9 requires 313.0560.
in the same way as 9a from 4d (0.49 g, 2.50 mmol) as white solid
(0.95 g, 89%). Mp 106e108 ꢁC; ½a D20
ꢀ53.2 (c 1.0, CHCl3); nmax (KBr
ꢃ
disc, cmꢀ1) 1757 (C]O), 1716 (C]O); dH (400 MHz, CDCl3) 7.82 (d,
1H, J 2.1 Hz, aromatic H-6), 7.78 (dd, 1H, J 8.6, 2.1 Hz, aromatic H-4),
7.43e7.31 (m, 5H, Bn ArH), 6.97 (d, 1H, J 8.6 Hz, aromatic H-3),
5.38e5.32 (m, 3H, overlapping of Glu H-2, H-3, H-4), 5.15 (sþd, 3H, J
7.3 Hz, overlapping of Glu H-1þBn CH2), 4.33 (q, 2H, J 7.1 Hz,
CH2CH3), 4.12 (d,1H, J 9.2 Hz, Glu H-5), 3.74 (s, 3H, OCH3), 2.04, 2.03,
1.82 (3ꢂ s, 3ꢂ 3H, Glu 3ꢂ OAc), 1.37 (t, 3H, J 7.2 Hz, CH2CH3). dC
(100.6 MHz, CDCl3) 170.3, 169.6, 169.4, 167.0, 160.0, 153.6, 145.6,
136.2, 128.9, 128.4, 127.5, 127.1, 123.7, 121.5, 113.5, 100.4 (OeCeO)
72.8, 72.1, 71.2, 71.0, 69.4, 61.1, 53.1, 20.8, 20.7, 20.5, 14.5; m/z (ESIþ)
611 [MþNa]þ, HRESIþ 611.1730, C29H32NaO13 requires 611.1741.
3.3.11. 4-Carboxy-2-methoxyphenyl-b-D-glucopyranosiduronic acid
(1b). Compound 1b was prepared in the same way as 1a from 9b
(1.90 g, 3.71 mmol) to give dipotassium salt as a white solid (1.23 g,
79%) after recrystallisation. Further acidification of the salt (0.60 g)
with Hþ cation exchange resin gave 1b as free acid (0.492 g 96%).
Compound 1b (dipotassium salt). White solid. Mp>240 ꢁC (dec);
½
a 2D0
ꢃ
ꢀ65.9 (c 0.25, H2O); nmax (KBr disc, cmꢀ1) 3219 (v br, OH), 1610
(C]O); dH (400 MHz, D2O) 7.58 (d, 1H, J 1.9 Hz, H-3), 7.51 (dd, 1H, J
8.42, 1.9 Hz, H-5), 7.19 (d, 1H, J 8.5 Hz, H-6), 5.21 (m, 1H, J 7.3 Hz, Glu
H-1), 3.92 (sþd, 4H, J 9.5 Hz, OCH3þGlu H-3), 3.71e3.60 (m, 3H, Glu
H-2, H-4 and H-5). dC (100 MHz, D2O) 175.3,174.6,147.8,147.8,131.3,
122.6, 114.8, 113.1, 99.9, 76.3, 75.2, 72.6, 71.6, 55.8; m/z (ESIꢀ) 343
[MþHꢀ2K]ꢀ, HRESIꢀ 343.0671, C14H15O10 requires 343.0665.
3.3.9. Methyl-(4-ethoxycarbonylphenyl-2-acetoxy-2,3,4-tri-O-ace-
tyl-
b
-
D
-glucopyranoside)uronate (9e) and methyl-(5-
-glucopyr-
ethoxycarbonylphenyl-2-acetoxy-2,3,4-tri-O-acetyl-
b-D
anoside)uronate (9f). Compounds 9e and 9f were prepared in the
same way as 9a from 4e/f (1.22 g, 5.44 mmol) as white solid
(1.95 g, 66%). Attempts to isolate the two isomers by silica column
chromatography with different eluent systems, such as DCM/
EtOAc, Pet ether/EtOAc and DCM/MeOH were not successful, nei-
ther was the crystallisation from different solvent system. The
following data are based on the strength of the peaks (9e:9f¼3:1).
Some signals are overlapped between the two isomers. Compound
9e: dH (400 MHz, CDCl3) 7.93 (dd, 1H, J 8.6, 2.1 Hz, H-5), 7.74 (d, 1H,
J 2.1 Hz, H-3), 7.07 (d, 1H, J 8.6 Hz, H-6), 5.38e5.32 (m, overlapping
signals, 3H, Glu H-2, H-3, H-4), 5.26e5.21 (m, 1H, Glu H-1), 4.35 (q,
2H, J 7.2 Hz, CH2CH3), 4.29e4.23 (m, 1H, Glu H-5), 3.76 (s, 3H,
CO2CH3), 2.28 (s, 3H, 3-OAc), 2.08, 2.06, 2.05 (3ꢂ s, 3ꢂ 3H, 3ꢂ Glu
OAc), 1.37 (t, 3H, J 7.2 Hz, CH2CH3); dC (100.6 MHz, CDCl3) 170.1,
Compound 1b. White solid. Mp>156 ꢁC (dec); ½a D20
ꢀ63.2 (c
ꢃ
0.25, H2O); nmax (KBr disc, cmꢀ1) 3415 (v br. OHþCOOH), 1704 (C]
O); dH (MeOD) 7.64 (dd, 1H, J 8.2, 2.0 Hz, H-5), 7.63 (d, J 8.3 Hz, H-3),
7.18 (d, 1H, J 8.3 Hz, H-6), 5.10 (m, 1H, J 7.6 Hz, Glu H-1), 3.99 (d, 1H, J
9.7 Hz, Glu H-3), 3.90 (s, 3H, OCH3), 3.65e3.49 (m, 3H, Glu H-2, H-4
and H-5). dC (D2O) 173.2,169.4, 149.2,147.7, 124.2, 123.7,114.6, 112.9,
99.5, 75.1, 75.0, 72.3, 71.2, 55.6; m/z (ESIꢀ) 343 [MꢀH]ꢀ, HRESIꢀ
343.0674, C14H15O10 requires: 343.0665.
3.3.12. 5-Carboxy-2-methoxyphenyl-b-D-glucopyranosiduronic acid
(1c). Compound 1c was prepared in the same way as 1a from 9c
(1.00 g, 1.95 mmol) to give a dipotassium salt (0.420 g, 62%) after