observation) with tetramethylsilane as internal standard. Mass
spectra in the chemical ionisation (CI) mode were obtained using
a VG7070E mass spectrometer. Both low and high resolution
electrospray mode (ES) mass spectra were obtained using a
Micromass LCT mass spectrometer operating in the +ve or -ve
ion mode as indicated. Elemental microanalysis was performed
by Mr. Steve Apter (Liverpool). 3-[2,2,3,3–2H4] Trimethylsilyl
propionate sodium salt (TSP), sodium dihydrogen phosphate
and disodium hydrogen phosphate, were purchased from Sigma-
Aldrich Company, Ltd (Gillingham, Dorset, UK). HPLC-NMR
grade deuterium oxide (2H2O) was obtained from Goss Scientific
Instruments (Essex, UK).
s, PhCH2CO), 3.66 (3 H, s, CH3O), 3.88 (1 H, d, J = 9.7 Hz, 5-H),
5.14 (2 H, AB qt, ArCH2O), 5.59 (1 H, d, J = 8.1 Hz, 1-H), 6.77
and 7.20 (4 H, dd, ArH of PMB ester) and 7.10–7.20 (5 H, m, ArH
of PhCH2); dC [(CD3)2CO] 41.5, 56.0, 67.6, 73.1, 73.9, 77.6 (x2),
96.0, 115.1, 128.2, 129.2, 129.6, 130.7, 131.2, 135.2, 161.1, 169.4
and 171.1; m/z (ES +ve mode) 455 (MNa+, 100%).
Benzyl 1-[(a-methyl)phenyl]acetyl-b-D-glucopyranuronates
10 and 11
Combined yield, 0.162 g (65%).
Diasteroisomer 1. White foam (0.077 g). Found: m/z,
439.1362. C22H24O8Na requires m/z, 439.1369; dH [(CD3)2CO] 1.33
(3H, d, J = 7.2 Hz, CH3CHAr), 3.28, 3.42 and 3.56 (3 H, 3 m,
2-H, 3-H and 4-H), 3.70 (1 H, q, J = 7.2 Hz, CH3CHAr), 3.93
(1 H, d, J = 9.2 Hz, 5-H), 5.07 (2 H, s, PhCH2O), 5.45 (1 H, d,
J = 8.2 Hz, 1-H) and 7.07–7.30 (10 H, m, ArH); dC [(CD3)2CO]
19.5, 39.2, 46.4, 67.7, 73.1, 77.6, 77.7, 96.0, 128.3, 128.9, 129.2,
129.3, 129.7, 129.8, 137.3, 141.6, 169.5 and 174.0; m/z (ES, +ve
ion mode) 439 (MNa+), 100%.
4-Methoxybenzyl-a,b-D-glucuronate 3
4-Methoxybenzyl bromide (0.94 mL, 5.67 mmol) was added
to a solution of D-glucuronic acid (1 g, 5.15 mmol) and 1M
TBAF in THF (5.41 mL, 5.15 mmol) in DMF (16 mL) which
was stirred at 20 ◦C. Stirring was continued for 16 h, then the
solution was evaporated to dryness and chromatographed, eluting
with 20% ethanol–dichloromethane. Evaporation of appropriate
fractions afforded the desired product 3 (1.15 g, 71%), which
was recrystallised from dichloromethane–ether as a white solid.
Found: C, 51.9; H, 5.6. C14H18O8·0.5 H2O requires C, 52.0; H,
5.9%. HRMS, found, m/z, 337.0905; C14H20O8Na requires m/z,
337.0899; dH [(CD3)2CO]: For 1a-OH anomer, 3.35–3.45 (1 H,
dd, 2-H) 3.65 (1 H, t, J = 9.0 Hz, 4-H), 3.73 (1 H, t, J =
8.9 Hz, 3-H), 3.82 (3H, s, CH3O), 4.31 (1 H, J = 9.3 Hz, 5-H),
5.10–5.20 (2 H, ABqt, ArCH2O), 5.17 (1 H, d, J = 3.1 Hz, 1-
H), 6.95 and 7.36 (4 H, approx. dd, ArH); for 1b-OH anomer:
3.22 (1H, t, 2-H), 3.40 (1H, t, 3-H), 3.65 (1H, t, J = 9.0 Hz,
4-H), 3.82 (3H, s, CH3O), 3.86 (1H, d, J = 9.8 Hz, 5-H), 4.57
(1H, d, J = 7.7 Hz, 1-H), 5.10–5.20 (2 H, ABqt, ArCH2O),
6.95 and 7.36 (4H, approx dd, ArH); dC [(CD3)2CO, mixture of
anomers] 56.0, 56.3, 67.2, 67.3, 73.2, 73.3, 73.6, 74.5, 76.2, 77.2,
94.3, 99.0, 115.1, 115.7, 129.3, 129.4, 131.1, 131.2, 136.1, 161.1,
162.7, 170.2 and 171.0; m/z (ES, +ve ion mode) 337 (MNa+),
100%.
Diasteroisomer 2. White foam (0.085 g). Found: m/z,
439.13680. C22H24O8Na requires m/z, 439.1369; dH [(CD3)2CO]
1.32 (3H, d, J = 7.2 Hz, CH3CHAr), 3.30, 3.45 and 3.53 (3 H, 3 m,
2-H, 3-H and 4-H), 3.70 (1 H, q, J = 7.2 Hz, CH3CHAr), 3.91
(1 H, d, J = 9.2 Hz, 5-H), 5.04 (2 H, s, PhCH2O), 5.48 (1 H, d, J =
8.2 Hz, 1-H) and 7.07–7.30 (10 H, m, ArH); dC [(CD3)2CO] 19.7,
39.2, 46.4, 67.7, 73.1, 77.6, 77.7, 96.0, 128.3, 128.9, 129.2, 129.3,
129.7, 129.8, 137.3, 141.7, 169.3 and 173.9 and 206.6 (solvent
signal); m/z (ES, +ve ion mode) 439 (MNa+), 100%.
Benzyl 1-[(a,a-dimethyl)phenyl]acetyl-b-D-glucopyranuronate 14
White foam, yield 0.155 g (60%). Found: m/z, 453.1515.
C23H26O8Na requires m/z, 453.1525; dH [(CD3)2CO] 1.55, 1.59
[6 H, 2 s, (CH3)2CAr], 3.40, 3.57 and 3.66 (3H, 3 m, 2-H, 3-H
and 4-H), 4.07 (1H, d, J = 9.5 Hz, 5-H), 5.21 (2 H, s, PhCH2O),
5.62 (1H, d, J = 8.1 Hz, 1-H) and 7.20–7.50 (10H, m, ArH);
dC [(CD3)2CO] 27.1, 27.7, 47.9, 67.6, 73.0, 73.9, 77.6, 77.7, 96.2,
127.0, 127.9, 129.1, 129.3, 129.5, 129.7, 137.3, 145.8, 169.4 and
176.0; m/z (ES, +ve ion mode) 453 (MNa+), 100%.
General procedure for the synthesis of benzyl or 4-methoxybenzyl
1-arylacetyl-b-D-glucopyranuronates 8, 10, 11 and 14
A mixture of the carboxylic acid 5, 6 or 7 (0.6 mmol), benzyl 233 or
4-methoxybenzyl D-glucuronate 3 (0.171 g, 0.6 mmol) and HATU
(0.228 g, 0.6 mmol) was stirred in anhydrous acetonitrile (6 mL)
with either NMM (0.22 mL, 0.202 g, 1.2 mmol) for 5 or DABCO
(0.134 g, 1.2 mmol) for 6 and 7. After optimum conversion
as determined by TLC (10% EtOH–CH2Cl2), the reaction was
quenched by addition of Amberlyst A-15 (H+ form, 2 eq.) followed
by brief stirring, filtration and evaporation. The crude product
was purified by chromatography, eluting with 5% EtOH–CH2Cl2
to afford the product 8, 10, 11 or 14 as a foam with spectroscopic
data as shown below.
1-(Phenyl)acetyl-b-D-glucopyranuronic acid 9
The PMB ester 8 (91 mg, 0.21 mmol) was treated with a solution
of 10% CF3CO2H in CH2Cl2 (0.91 mL) at 0 ◦C. After stirring
for 3 h at 20 ◦C, the solvent was removed in vacuo and the
residue was triturated with CH2Cl2, affording a solid which was
filtered off, washed with further CH2Cl2 and dried to afford the
desired product 9 (54 mg, 82%). The spectroscopic data of this
compound were consistent with those previously described,33 viz:
dH [(CD3)2CO]: 3.32–3.38 (1H, t, 2-H), 3.43–3.50 (1H, t, 3-H),
3.52–3.59 (1H, t, 4-H) 3.61 (2H, s, CH2), 3.86 (1H, d, J = 9.7 Hz,
5-H), 5.48 (1H, d, J = 8.0 Hz, 1-H) and 7.15–7.20 (5H, m, ArH);
dC [(CD3)2CO]: 41.5, 72.9, 73.9, 77.1, 77.6, 95.9, 128.2, 129.6,
130.8,135.2, 170.4 and 171.2; m/z (ES -ve ion mode) 311 [M - H]-
100%.
4-Methoxybenzyl (1-phenyl)acetyl-b-D-glucopyranuronate 8
Yield 41%, white solid. Found: C, 60.35; H, 5.7; m/z, 455.1321.
C22H24O9·0.5 H2O requires C, 59.9; H, 5.7%; C22H24O9Na requires
m/z, 455.1318; dH [(CD3)2CO] 3.32 (1 H, t, J = 8.5 Hz, 2-H), 3.43
(1 H, t, J = 9.0 Hz, 3-H), 3.54 (1 H, t, J = 9.3 Hz, 4-H), 3.60 (2 H,
This journal is
The Royal Society of Chemistry 2009
Org. Biomol. Chem., 2009, 7, 2525–2533 | 2531
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