L. Cattiaux et al. / Bioorg. Med. Chem. 19 (2011) 547–555
553
JH3H2 = JH3H4 = 4.8 Hz, JH3OH = 0.7 Hz, H3), 7.22–8.00 (m, 15H, H Ar).
13C NMR (100 MHz, CDCl3) d (ppm): 14.3 (CH3 Ethyl), 24.7 (C8 or
3.3.14. 5-Carboxyethylpentyl 2,3,6-tri-O-benzoyl-5-O-levulinyl-
b- -galactofuranosyl)-(1?5)-2,3,6-tri-O-benzoyl-b-
D
D-
C10), 25.7 (C9), 29.1 (C8 or C10), 34.2 (C11), 60.2 (CH2 Ethyl), 66.2
galactofuranosyl)-(1?5)-2,3,6-tri-O-benzoyl-b-D-
(C6), 67.3 (C7), 69.1 (C5), 78.1 (C3), 81.5 (C2), 83.1 (C4), 105.7 (C1),
128.4–133.6 (C Ar), 165.3–166.5 (3 CO Bz), 173.6 (COOEt).
galactofuranoside (13)
To a mixture of 12 (883 mg, 0.797 mmol, 1 equiv) and 8
(720 mg, 0.956 mmol, 1.2 equiv) and molecular sieves 4Å (1.00 g)
in anhydrous CH2Cl2 (10 mL), were added at 0 °C under argon:
3.3.12. 5-Carboxyethylpentyl 5-O-(2,3,6-tri-O-benzoyl-5-O-
levulinyl-b-
D
-galactofuranosyl)-2,3,6-tri-O-benzoyl-b-
D-
NBS (355 mg, 2.00 mmol, 2.5 equiv) and TfOH (35 lL, 0.40 mmol,
galactofuranoside (11)
0.5 equiv). After 30 min, the mixture was filtered and successively
washed with saturated aqueous Na2S2O3, NaHCO3, and brine. The
organic layer was dried over MgSO4, filtered and concentrated.
The residue was purified by column chromatography on silica gel
(Cyhex/EtOAc 7:3) to give 911 mg of 13 (68%) as a white foam.
To a mixture of 10 (1.158 g, 1.83 mmol, 1 equiv) and 8 (1.511 g,
2.00 mmol, 1.1 equiv) and molecular sieves 4Å (1.00 g) in anhy-
drous CH2Cl2 (30 mL), were added at 0 °C under argon: NBS
(814 mg, 4.57 mmol, 2.5 equiv) and TfOH (80 lL, 0.91 mmol,
0.5 equiv). After 30 min, the mixture was filtered, and successively
washed with saturated aqueous Na2S2O3, NaHCO3, and brine. The
organic layer was dried over MgSO4 and concentrated. The residue
was purified by column chromatography on silica gel (Cyhex/
EtOAc 7:3) to give 1.31 g of 11 (60%) as a white foam. Rf: 0.24 (Cy-
hex/EtOAc 7:3). MS DCI+-HRMS m/z [M+NH4]+ calcd for
Rf: 0.11 (Cyhex/EtOAc 7:3). ½a D25
ꢂ
-1 (c 1, CHCl3). MS FAB+-HRMS
m/z [M+Na]+ calcd for C94H88NaO29 1703.5309, found 1703.5341.
1H NMR (400 MHz, CDCl3) d (ppm): 1.29 (t, 3H, J = 7.1 Hz, CH3
Ethyl), 1.42 (m, 2H, H9), 1.63–1.73 (m, 4H, H8, H10), 2.11 (s, 3H,
CH3 Lev), 2.29 (t, 2H, J = 7.5 Hz, H11), 2.40–2.70 (m, 4H, 2CH2
Lev), 3.47 (dt, 1H, JH7aH7b = 9.6 Hz, JH7aH8 = 5.3 Hz, H7a), 3.81 (dt,
1H, JH7bH7a = 9.6 Hz, JH7bH8 = 6.6 Hz, H7b), 4.09 (q, 2H, J = 7.1 Hz,
C
67H70NO21 1224.4435, found 1224.4430. ½a D25
ꢂ
+2 (c 1, CHCl3). 1H
NMR (400 MHz, CDCl3) d (ppm): 1.29 (t, 3H, J = 7.1 Hz, CH3 Ethyl),
1.43 (m, 2H, H9), 1.63–1.73 (m, 4H, H8, H10), 2.11 (s, 3H, CH3 Lev),
2.30 (t, 2H, J = 7.5 Hz, H11), 2.55–2.75 (m, 4H, 2CH2 Lev), 3.61 (dt,
1H, JH7aH7b = 9.6 Hz, JH7aH8 = 5.3 Hz, H7a), 3.80 (dt, 1H,
JH7bH7a = 9.6 Hz, JH7bH8 = 6.6 Hz, H7b), 4.09 (q, 2H, J = 7.1 Hz, CH2
CH2 Ethyl), 4.30–4.52 (m, 2H, H4, H6b), 4.65–4.82 (m, 7H, H5, H5a,
2H6, 2H6a, H6b), 4.88–4.93 (m, 2H, H4a, H4b), 5.40 (s, 1H, H1), 5.49
(d, 1H, JH2H3 = 0.9 Hz, H2), 5.55 (dd, 1H, JH3bH4b = 5.2 Hz,
JH3bH2b = 1.8 Hz, H3b), 5.71 (d, 1H, JH2aH3a = 1.6 Hz, H2a), 5.74 (d,
1H, JH2bH3b = 1.8 Hz, H2b), 5.75–5.80 (m, 3H, H1a, H1b, H5b), 5.83–
5.88 (m, 2H, H3, H3a), 7.30–8.30 (m, H Ar). 13C NMR (100 MHz,
CDCl3) d (ppm): 14.2 (CH3 Ethyl), 24.6 (C8 or C10), 25.6 (C9), 27.8
(CH2 Lev), 29.1 (C8 or C10), 29.5 (CH3 Lev), 34.1 (H11), 37.8 (CH2
Lev), 60.2 (CH2 Ethyl), 63.6 (C6b), 64.3 (C6), 65.0 (C6a), 67.1 (C7),
70.0 (C5b), 73.0–73.1(C5, C5a), 77.0–77.1 (C3, C3a, C3b), 81.6–81.8
(C2, C2a, C2b, C4a), 82.5 (C4b), 105.1–105.3 (C1, C1a, C1b), 128.0–
132.8 (C Ar), 165.0–166.1 (CO Bz), 171.9 (CO ester Lev), 173.5
(COOEt), 205.8 (CO ketone Lev).
Ethyl), 4.50–4.58 (m, 2H, H4, H6a), 4.68–4.83 (m, 4H, H5, H6a
,
2H6), 4.92 (t, 1H, JH4aH3a = JH4aH5a = 4.7 Hz, H4a), 5.25 (s, 1H, H1),
5.49 (d, 1H, JH2H3 = 1.4 Hz, H2), 5.42 (dd, 1H, JH3aH4a = 5.2 Hz, JH3a-
H2a = 1.6 Hz, H3a), 5.73–5.75 (d, 1H, JH2aH3a = 1.6 Hz, H2a), 5.75–
5.85 (m, 3H, H1a, H3, H4a), 7.20–8.20 (m, H
Ar). 13C NMR
(100 MHz, CDCl3) d (ppm): 14.2 (CH3 Ethyl), 24.6 (C8 or C10), 25.6
(C9), 27.9 (CH2 Lev), 29.1 (C8 or C10), 39.5 (CH3 Lev), 34.1 (H11),
37.8 (CH2 Lev), 60.1 (CH2 Ethyl), 63.2 (C6), 64.5 (C6a), 67.2 (C7),
70.0 (C5a), 73.1 (C5), 76.7–77.0 (C3, C3a), 81.6–81.7 (C2, C2a, C4a),
82.2 (C4), 105.2 (C1a), 105.4 (C1), 128.1–133.4 (C Ar), 165.1–166.0
(6 CO Bz), 171.9 (CO ester Lev), 173.5 (COOEt), 205.8 (CO ketone
Lev).
3.3.15. 5-Carboxyethylpentyl (2,3,6-tri-O-benzoyl-b-D-
galactofuranosyl)-(1?5)-2,3,6-tri-O-benzoyl-b-
galactofuranosyl)-(1?5)-2,3,6-tri-O-benzoyl-b-
galactofuranoside (14)
D
-
-
D
3.3.13. 5-Carboxyethylpentyl 5-O-(2,3,6-tri-O-benzoyl-b-
galactofuranosyl)-2,3,6-tri-O-benzoyl-b-D-galactofuranoside
(12)
D
-
Compound 13 (911 mg, 0.542 mmol, 1 equiv) was dissolved in a
0.5 M solution of hydrazine monohydrate (6 mL) in pyridine/AcOH
(4:1). The mixture was stirred at room temperature for 30 min and
concentrated. The residue was dissolved in CH2Cl2, washed with
(1 M) HCl and NaHCO3. The organic layer was dried over MgSO4
and concentrated. The residue was purified by column chromatog-
raphy on silica gel (Cyhex/EtOAc 7:3) to give 598 mg of 14 (70%) as
Compound 11 (1.00 g, 0.83 mmol) was dissolved in a 0.5 M
solution of hydrazine monohydrate (8 mL) in pyridine/AcOH
(4:1). The mixture was stirred at room temperature for 30 min
and concentrated. The residue was dissolved in CH2Cl2, washed
with aq HCl (1 M) and NaHCO3. The organic layer was dried over
MgSO4 and concentrated. The residue was purified by column
chromatography on silica gel (Cyhex/EtOAc 7:3) to give 883 mg
a syrup. Rf: 0.50 (Cyhex/EtOAc 6:4). ½a D25
ꢁ3.0 (c 1, CHCl3). MS
ꢂ
FAB+-HRMS m/z [M+Na] calcd for C89H82NaO27 1605.4941 found
1605.4941. 1H NMR (400 MHz, CDCl3) d (ppm): 1.29 (t, 3H,
J = 7.1 Hz, CH3 Ethyl), 1.42 (m, 2H, H9), 1.63–1.73 (m, 4H, H8,
H10), 2.30 (t, 2H, J = 7.5 Hz, H11), 2.86 (d, 1H, JOHH5b = 7.3 Hz, OH),
3.47 (dt, 1H, JH7aH7b = 9.6 Hz, JH7aH8 = 5.3 Hz, H7a), 3.80 (dt, 1H,
JH7bH7a = 9.6 Hz, JH7bH8 = 6.6 Hz, H7b), 4.09 (q, 2H, J = 7.1 Hz, CH2
Ethyl), 4.40 (broad s, 1H, H5b), 4.48–4.50 (m, 2H, 2H6b), 4.51–4.55
of 12 (96%) as a syrup. Rf: 0.35 (Cyhex/EtOAc 7:3). ½a D25
ꢁ4 (c 3,
ꢂ
CHCl3). MS DCI+-HRMS m/z [M+Na]+ calcd for C62H60O19Na
1131.3629, found 1131.3624. 1H NMR (400 MHz, CDCl3) d (ppm):
1.29 (t, 3H, J = 7.1 Hz, CH3 Ethyl), 1.43 (m, 2H, H9), 1.63–1.73 (m,
4H, H8, H10), 2.30 (t, 2H, J = 7.5 Hz, H11), 2.86 (d, 1H, JOHH5a = 8.0 Hz,
OH), 3.47 (dt, 1H, JH7aH7b = 9.6 Hz, JH7aH8 = 5.3 Hz, H7a), 3.80 (dt, 1H,
JH7bH7a = 9.6 Hz, JH7bH8 = 6.6 Hz, H7b), 4.09 (q, 2H, J = 7.1 Hz, CH2
Ethyl), 4.45 (br, 1H, H5), 4.53–4.58 (m, 3H, H4, H6a), 4.68–4.83
(m, 3H, H4, H6), 5.20 (s, 1H, H1), 5.49 (d, 1H, JH2H3 = 1.5 Hz, H2),
5.70 (dd, 1H, JH3aH2a = 1.7 Hz, JH3aH4a = 5.1 Hz, H3a), 5.78 (d, 1H, JH2a-
H3a = 1.7 Hz, H2a), 5.80 (s, 1H, H1a), 5.84 (dd, 1H, JH3H2 = 1.5 Hz,
JH3H4 = 5.2 Hz, H3), 7.30–8.20 (m, H Ar). 13C NMR (100 MHz, CDCl3)
d (ppm): 14.2 (CH3 Ethyl), 24.6 (C8 or C10), 25.6 (C9), 29.1 (C8 or
(dd, 1H, JH4H3 = 5.3 Hz, JH4H5 = 3.5 Hz, H4), 4.65–4.83 (m, 7H, H4b
,
H5, H5a, 2H6, 2H6a), 4.93 (dd, 1H, J = 5.1 Hz, J = 2.8 Hz, H4a), 5.32
(s, 1H, H1), 5.50 (d, 1H, JH2H3 = 1.2 Hz, H2), 5.69 (dd, 1H,
JH3bH4b = 5.2 Hz, JH3bH2b = 1.9 Hz, H3b), 5.72 (d, 1H, JH2aH3a = 1.5 Hz,
H
2a), 5.76 (d, 1H, JH2bH3b = 1.9 Hz, H2b), 5.79 (1s, 1H, H1a), 5.80 (s,
1H, H1b), 5.83–5.90 (m, 2H, H3, H3a), 7.30–8.30 (m, H Ar). 13C
NMR (100 MHz, CDCl3): d (ppm) 14.2 (CH3 Ethyl), 24.7 (C8 or
C10), 25.6 (C9), 29.0 (C8 or C10), 34.1 (H11), 60.1 (CH2 Ethyl), 64.4–
C
10), 34.3 (H11), 60.2 (CH2 Ethyl), 64.6 (C6), 66.1 (C6a), 67.2 (C7),
65.0 (C6, C6a), 66.2 (C6b), 67.1 (C7), 69.4 (C5b), 73.0–73.1 (C5, C5a),
77.0–77.1 (C3, C3a), 77.8 (C3b), 81.6 (C2, C2b), 81.8 (C2a), 82.5 (C4),
82.8 (C4a), 83.5 (C4b), 105.1 (C1a or C1b), 105.4 (C1), 105.6 (C1a or
69.4 (C5a), 73.8 (C5), 77.0 (C3), 78.0 (C3a), 81.6 (C2a), 81.8 (C2),
82.1 (C4), 83.5 (C5), 105.5 (C1, C1a), 128.1–133.4 (C Ar), 165.1–
166.4 (6 CO Bz), 173.6 (COOEt).
C1b), 128.1–133.4 (C ar), 165.0–166.3 (9 CO Bz), 173.5 (COOEt).