Glucose Derivatives of Iminodiacetic Acid
1,3,5,6-Tetr a -O-a cetyl-2-O-[2-[bis-N-[(1-m eth oxyca r bo-
n yl)m eth yl]a m in oeth oxy]eth oxy]eth yl-r,â-D-glu cop yr a -
n ose (9c). Compound 9c was prepared from 8c according to
the preparation of 9a : yield 41%; Rf 0.44 (AcOEt); 1H NMR δ
6.24 (dd, J ) 8.5, 4.3 Hz, 0.06H), 6.04 (d, J ) 11.4 Hz, 0.27H),
5.86 (d, J ) 5.5 Hz, 0.17H), 5.74 (d, J ) 5.2 Hz, 0.27H), 5.74
(d, J ) 8.2 Hz, 0.23H), 5.41-5.17 (m, 2H), 5.13-5.06 (m, 0.5H),
4.81-4.36 (m, 1.5H), 4.33-4.19 (m, 0.8H), 4.17-3.96 (m, 2.2H),
3.89-3.41 (m, 10.99H), 3.63 (s, 6H), 3.39 (s, 0.81H), 3.36 (s,
0.69H), 3.28 (s, 0.51H); 2.93-2.83 (m, 2H), 2.09-1.94 (m, 12H);
MS m/z 646.2 (MNa+). Anal. Calcd for C26H41NO16 (623.61):
C, 50.08; H, 6.63; N, 2.25. Found: C, 50.17; H, 6.37, N, 2.29.
MS m/z 484.3(MNa+). Anal. Calcd for C24H31NO8 (461.206):
C, 62.46; H, 6.77; N, 3.04. Found: C, 62.47; H, 6.82; N, 3.20.
1,2:3,5-(O-Met h ylen e)-6-O-(3-a m in op r op yl)-r-D-glu co-
fu r a n ose (13a ). Compound 13a was prepared from 12a
according to the preparation of 6a : yield 91%; Rf 0.15 (CH2-
20
1
Cl2/acetone, 95:5); [R]D ) +13.4, c 0.047, MeOH; H NMR δ
5.99 (d, J ) 3.6 Hz, 1H), 5.04 (d, J ) 4.8 Hz, 1H), 5.01 (d, J )
4.8 Hz, 1H), 4.88 (s, 2H), 4.53 (d, J ) 3.3 Hz, 1H), 4.24-4.22
(m, 1H), 4.05-4.01 (m, 2H), 3.83-3.74 (m, 3H), 3.65-3.57 (m,
1H), 3.30-3.19 (m, 2H), 2.04-1.99 (m, 2H); 13C NMR δ 105.1
(t), 104.9 (t), 97.0 (d, 2C), 88.5 (t, 2C), 84.2 (t), 84.0 (t), 71.6
(d), 66.4 (d). Anal. Calcd for C11H19NO6 (261.12): C, 50.57; H,
7.33; N, 5.36. Found: C, 50.25; H, 7.00; N, 5.63.
2-O-[Bis(car boxym eth yl)am in opr opyl]-r,â-D-glu co pyr -
a n ose (10a ). NaOMe (13.4 mg, 0.25 mmol, 1 equiv) was added
to a solution of 9a (137.2 mg, 0.25 mmol, 1 equiv) in dry
methanol (1 mL) at rt under nitrogen flux. After 3 h of reaction
the solvent was removed, and the product was dissolved in
NaOH (0.091 N, 1 mL) and stirred overnight. The solution was
neutralized by addition of Dowex 50W-X8 till pH 7 was
attained. The solution was then filtered and evaporated to
1,2:3,5-(O-Meth ylen e)-6-O-(8-am in ooctyl)-r-D-glu cofu r a-
n ose (13b). Compound 13b was prepared from 12b according
to the preparation of 6b: yield 81%; Rf 0.33 (CH2Cl2/acetone,
20
95:5); [R]D ) -12, c 0.00084, MeOH; IR (neat) 1708, 1634
cm-1; 1H NMR δ 6.13 (d, J ) 3.9 Hz, 1H), 5.23 (d, J ) 6.0 Hz,
1H), 5.20-5.10 (m, 2H), 4.88 (d, J ) 6.0 Hz, 1H), 4.56 (d, J )
4.8 Hz, 1H), 4.46 (d, J ) 2.4 Hz, 1H), 4.29-4.20 (m, 1H), 4.17-
4.09 (m, 1H), 3.92-3.81 (m, 1H), 3.81-3.70 (m, 1H), 3.56-
3.45 (m, 2H), 2.96-2.84 (m, 2H), 2.90-1.05 (m, 12H); 13C NMR
δ 105.2, 104.8, 97.2, 84.5, 76.9, 76.6, 72.8, 72.5, 72.3, 72.0, 32.3,
30.2, 29.9, 27.4, 26.8, 23.3; MS m/z 332.3 (MH+). Anal. Calcd
for C16H29NO6 (331.20): C, 57.99; H, 8.82; N, 4.23. Found: C,
58.37; H, 8.56; N, 4.34.
1
afford an oil: yield 85%; IR (neat) 1632, 1402 cm-1; H NMR
(CD3OD) δ 5.44 (m, 0.5H), 4.72 (d, J ) 8.1 Hz, 0.5H), 4.26-
3.59 (m, 8H), 3.56-3.45 (m, 2H), 3.39-3.10 (m, 1H), 3.21-
3.18 (m, 0.5H), 3.06-2.92 (m, 0.5H), 2.28-2.01 (m, 2H), 1.56-
1.40 (m, 2H); MS m/z 357.0 (MH4+). Anal. Calcd for C13H23NO10
(353.13): C, 44.19; H, 6.56; N, 3.96. Found: C, 43.83; H, 6.57;
N, 3.62.
6-O-[Bis-N-[(1-m eth oxycar bon yl)m eth yl]am in opr opyl]-
1,2:3,5-(O-m eth ylen e)-r-D-glu cofu r a n ose (14a ). Compound
14a was prepared from 13a according to the preparation of
7a , AcOEt/nHex (1:2): yield 58%; Rf 0.87 (CH2Cl2/acetone, 95:
5); [R]D20 ) -37.9, c 0.0380, MeOH; 1H NMR δ 5.88 (d, J ) 3.7
Hz, 1H), 5.04-4.89 (m, 3H), 4.79-4.67 (m, 1H), 4.39 (dd, J )
8.7, 3.7 Hz, 1H), 4.23 (dd, J ) 12.7, 1.7 Hz, 1H), 4.08-4.01
(m, 1H), 3.95-3.90 (m, 1H), 3.72-3.54 (m, 2H), 3.62 (s, 6H),
3.56-3.34 (m, 2H), 3.47 (s, 4H), 2.77-2.68 (m, 2H), 1.75-1.61
(m, 2H); 13C NMR δ 146.4, 140.0, 105.1, 104.9, 97.3, 97.2, 88.9,
88.5, 84.3, 76.6, 76.4 (2C), 72.2, 72.1, 68.6 (2C), 68.5; MS m/z
428.3 (MNa+). Anal. Calcd for C17H27NO10 (405.16): C, 50.37;
H, 6.71; N, 3.46. Found: C, 50.56; H, 6.37; N, 3.48.
2-O-[Bis(ca r boxym eth yl)a m in ooctyl]-r,â-D-glu cop yr a -
n ose (10b). Compound 10b was prepared from 9b according
to the preparation of 10a : yield 89%; IR (neat) 1596, 1354
1
cm-1; H NMR (CD3OD) δ 5.37 (d, J ) 3.3 Hz, 0.5H), 4.64-
4.59 (m, 0.5H), 4.12-3.56 (m, 9H), 3.52-3.45 (m, 1H), 3.39-
3.34 (m, 1H), 3.34-3.22 (m, 2.5H), 3.01 (dd, J ) 8.7, 8.1 Hz,
0.5H), 1.89-1.78 (m, 2H), 1.76-1.65 (m, 2H), 1.57-1.40 (m,
8H); MS m/z 423.2 (M). Anal. Calcd for C18H33NO10 (423.21):
C, 51.05; H, 7.85; N, 3.31. Found: C, 51.00; H, 7.88; N, 3.46.
2-O-[2-[Bis(ca r boxym eth yl)a m in oeth oxy]eth oxy]eth yl-
r,â-D-glu cop yr a n ose (10c). Compound 10c was prepared
from 9c according to the preparation of 10a : yield 81%; 1H
NMR (CD3OD) δ 5.48-5.35 (m, 0.45H), 5.26-5.10 (m, 0.55H),
4.60-4.49 (m, 0.5H), 4.08-3.81 (m, 2H), 3.76-3.48 (m, 1.5H),
3.36-3.10 (m, 3H), 3.10-2.75 (m, 13H), 2.39-2.25 (m, 2H);
MS m/z 427.3 (M). Anal. Calcd for C16H29NO12 (427.17): C,
44.96; H, 6.84; N, 3.28. Found: C, 44.89; H, 6.82; N, 3.15.
6-O-[Bis-N-[(1-m eth oxyca r bon yl)m eth yl]a m in ooctyl]-
1,2:3,5-(O-m eth ylen e)-r-D-glu cofu r a n ose (14b). Compound
14b was prepared from 13b according to the preparation of
7a : yield 62%; [R]D20 ) +122, c 0.0043, MeOH; IR (neat) 1746,
1
1660 cm-1; H NMR δ 6.15 (d, J ) 3.9 Hz, 1H), 5.25 (d, J )
6.0 Hz, 1H), 5.21-5.19 (m, 1H), 5.19-5.16 (m, 1H), 4.90 (d, J
) 5.7 Hz, 1H), 4.58 (d, J ) 3.9 Hz, 1H), 4.48 (d, J ) 1.8 Hz,
1H), 4.24-4.20 (m, 1H), 4.18-4.15 (m, 1H), 3.86-3.82 (m, 1H)
3.81 (s, 6H), 3.80-3.76 (m, 1H), 3.66 (s, 4H), 3.59-3.50 (m,
2H), 2.79 (dd, J ) 7.5, 5.4 Hz, 2H), 1.73-1.29 (m, 12H); MS
m/z 498.6 (MNa+); HRMS m/z calcd for C22H37NO10 475.2417,
found 475.2426.
6-O-(3-ter t-Bu toxycar bon ylam in opr opyl)-1,2:3,5-(O-m e-
th ylen e)-r-D-glu cofu r a n ose (12a ). Compound 12a was pre-
pared from 1,2:3,5-(O-methylene)-R-D-glucofuranose (11) and
3-bromo-N-(1-tert-butoxycarbonyl)propylamine according to
the preparation of 5a : yield 57%; Rf 0.38 (CH2Cl2/acetone, 95:
20
5); [R]D ) +0.7, c 0.008, MeOH; IR (neat), 2922, 1710 cm-1
;
1H NMR δ 6.01 (d, J ) 3.9 Hz, 1H), 5.12-4.97 (m, 4H), 4.82
(dd, J ) 9.4, 5.9 Hz, 1H), 4.46 (dd, J ) 9.4, 3.9 Hz, 1H), 4.32
(dd, J ) 6.5, 2.4 Hz, 1H), 4.15-4.08 (m, 1H), 4.03-3.99 (m,
1H), 3.76 (dd, J ) 10.5, 3.9 Hz, 1H), 3.66 (dd, J ) 10.5, 4.8
Hz, 1H), 3.59-3.41 (m, 2H), 3.28-3.11 (m, 2H), 1.82-1.70 (m,
6-O-[Bis(ca r boxym eth yl)a m in op r op yl]-r,â-D-glu cop y-
r a n ose (15a ). Compound 14a (117 mg, 0.29 mmol, 1 equiv)
was dissolved in a 1 M solution of NaOH (1 mL). After 2 h of
stirring at rt, the solution was neutralized by addition of
Dowex 50W-X8 till pH 5-6 was attained. The solution was
then filtered and evaporated to afford an oil: yield 78%; IR
2H), 1.42 (s, 9H); MS m/z 384.3 (MNa+). Anal. Calcd for C16H27
-
1
(neat) 1716, 1654, 1560 cm-1; H NMR (CD3OD) δ 5.94 (d, J
NO8 (361.17): C, 53.18; H, 7.53; N, 3.88. Found: C, 53.17; H,
7.26; N, 4.01.
) 3.9 Hz, 0.5H), 5.09 (d, J ) 6.3 Hz, 0.5H), 5.07-5.02 (m, 1H),
5.01-4.96 (m, 1H), 4.70 (d, J ) 6.6 Hz, 0.5H), 4.54-4.39 (m,
0.5H), 4.39-4.28 (m, 0.5H), 4.17-3.92 (m,1.5H), 3.86-3.65 (m,
1H), 3.76 (s, 2H), 3.74 (s, 2H), 3.56-3.47 (m, 2H), 3.43-2.30
(m, 2H), 1.89-1.76 (m, 2H); MS m/z 356.1 (MH3+). Anal. Calcd
for C13H23NO10 (353.13): C, 44.19; H, 6.56; N, 3.96. Found:
C, 44.05; H, 6.61; N, 4.08.
1,2:3,5-(O-Meth ylen e)-6-O-(8-ph th alim idooctyl)-r-D-glu -
cofu r a n ose (12b). Compound 12b was prepared from 11 and
N-bromooctylphthalimide according to the preparation of 5a :
20
yield 40%; Rf 0.33 (CH2Cl2/acetone, 95:5), [R]D ) +18.0, c
1
0.0183, MeOH; IR (neat) 1772, 1712, 1400 cm-1; H NMR δ
8.08-7.89 (m, 2H), 7.57-7.34 (m, 2H), 5.97 (d, J ) 3.6 Hz,
1H), 5.12-4.94 (m, 3H), 4.75 (dd, J ) 6.0, 5.7 Hz, 1H), 4.42
(dd, J ) 8.4, 3.9 Hz, 1H), 4.30 (dd, J ) 12.0, 2.4 Hz, 1H), 4.13-
4.02 (m, 1H), 4.00-3.95 (m, 1H), 3.73 (dd, J ) 10.5, 3.6 Hz,
1H), 3.62 (dd, J ) 10.5, 4.8 Hz, 1H), 3.45-3.26 (m, 4H), 1.69-
1.43 (m, 4H), 1.42-1.16 (m, 8H); 13C NMR δ 166.1 (2C), 134.7,
134.2, 132.7 (2C), 124.0, 123.3, 105.0, 104.5, 97.1, 78.1, 76.8,
76.4, 72.7, 72.3, 72.2, 71.8, 30.0, 29.7, 29.6, 29.1, 27.3, 26.6;
6-O-[Bis(ca r boxym eth yl)a m in ooctyl]-r,â-D-glu cop yr a -
n ose (15b). Compound 15b was prepared from 14b according
to the preparation of 9a : yield 77%; IR (neat) 1602, 1402 cm-1
;
1H NMR (CD3OD) δ 6.14 (d, J ) 6.5 Hz, 0.6H), 5.18-5.09 (m,
2.4H), 4.70-4.64 (m, 1H), 4.59 (s large, 1H), 4.39-4.32 (m,
1H), 4.13-3.98 (s large, 1H), 4.08-3.96 (m, 1H), 3.85 (s large,
1H), 3.81-3.59 (m, 4H), 3.34-3.02 (m, 2H), 1.84-1.32 (m,
J . Org. Chem, Vol. 68, No. 2, 2003 517