J. L. de Paz, M. Martín-Lomas
FULL PAPER
6.0 Hz, 1 H, 5D-H), 4.25 (m, 2 H, 2A-H, 6E-H), 4.18–3.99 (m, 7
H, 4A-H, 5A-H, 3B-H, 4B-H, 4C-H, 3D-H, 4D-H), 3.96–3.85 (m,
5D-H, 6ЈA-H, CH2Ph), 4.39 (m, 1 H, 6ЈE-H), 4.24 (ddd, J1,2
3.5 Hz, 1 H, 2A-H), 4.14–3.95 (m, 8 H, 4A-H, 5A-H, 3B-H, 4B-H,
=
4 H, CH(CH3)2, 5C-H, 3E-H, 4E-H), 3.80–3.65 (m, 5 H, 3A-H, 4C-H, 3D-H, 4D-H, 5E-H), 3.87–3.83 (m, 2 H, CH(CH3)2, 5C-H),
3C-H, 6C-H, 5E-H, 6ЈE-H), 3.55 (s, 3 H, COOCH3), 3.54 (m, 1 H, 3.77 (m, 1 H, 6C-H), 3.72–3.57 (m, 4 H, 3A-H, 3C-H, 3E-H, 4E-
6ЈC-H), 3.43 (dd, 1 H, 2D-H), 3.36 (m, 2 H, 2C-H, 2E-H), 3.30 (s, H), 3.56 (s, 3 H, COOCH3), 3.52 (m, 1 H, 6ЈC-H), 3.41 (dd, 1 H,
3 H, COOCH3), 1.84 (s, 3 H, NHCOCH3), 1.24 (s, 9 H, OC- 2D-H), 3.35 (dd, J1,2 = 3.8, J2,3 = 10.5 Hz, 1 H, 2C-H), 3.27 (s, 3
OC(CH3)3), 1.24–1.12 (2d, 6 H, J = 6.0 Hz, CH(CH3)2) ppm. 13C
NMR (125 MHz, CDCl3): δ = 177.4, 169.7, 169.5, 169.4, 166.2,
138.8–126.2 (Ph), 101.5, 100.1, 99.7, 98.3, 97.8, 95.9, 82.6, 81.5,
H, COOCH3), 3.23 (dd, J1,2 = 3.3, J2,3 = 9.8 Hz, 1 H, 2E-H), 1.82
(s, 3 H, NHCOCH3), 1.21 (s, 9 H, OCOC(CH3)3), 1.21–1.09 (2d, J
= 6.0 Hz, 6 H, CH(CH3)2) ppm. 13C NMR (125 MHz, CDCl3): δ
79.0, 78.5, 78.2, 76.2, 76.1, 75.6, 75.48, 75.46, 75.1, 74.8, 74.7, 74.6, = 177.4, 169.8, 169.51, 169.46, 167.2, 166.2, 138.7–127.8 (Ph),
73.9, 73.8, 73.5, 72.3, 71.6, 71.2, 71.0, 70.4, 69.5, 68.6, 67.3, 63.4,
62.9, 62.8, 52.2, 51.9, 51.7, 38.9, 27.2, 23.4, 23.3, 21.7, 21.5 ppm.
100.1, 99.1, 98.3, 97.7, 95.8, 81.2, 78.7, 78.5, 78.0, 76.24, 76.18,
75.6, 75.2, 74.9, 74.8, 74.61, 74.58, 73.91, 73.85, 73.5, 72.2, 71.6,
C105H117N7O28 (1925.1): C 65.51, H 6.13, N 5.09; found C 65.39, 71.2, 71.0, 70.6, 70.4, 69.5, 67.3, 63.0, 62.8, 52.2, 51.9, 51.7, 38.9,
H 5.93, N 5.13.
27.1, 23.4, 23.3, 21.7 ppm. C105H117N7O29·H2O (1959.2): C 64.37,
H 6.12, N 5.00; found C 64.29, H 6.13, N 5.01.
Isopropyl
O-(2-Azido-3-O-benzyl-2-deoxy-α-D-glucopyranosyl)-
(1Ǟ4)-O-(Methyl
(1Ǟ4)-O-(2-Azido-3,6-di-O-benzyl-2-deoxy-α-
(1Ǟ4)-O-(Methyl 3-O-Benzyl-2-O-pivaloyl-α-
2,3-Di-O-benzyl-α-
L
-idopyranosyluronate)- Isopropyl O-(Methyl 2-O-Benzoyl-3,4-di-O-benzyl-α-
-glucopyranosyl)- uronate)-(1Ǟ4)-O-(2-Azido-6-O-benzoyl-3-O-benzyl-2-deoxy-α-
-idopyranosyluron- glucopyranosyl)-(1Ǟ4)-O-(Methyl 2,3-Di-O-benzyl-α- -idopyranos-
ate)-(1Ǟ4)-2-acetamido-6-O-benzoyl-3-O-benzyl-2-deoxy-α- -glu- yluronate)-(1Ǟ4)-O-(2-Azido-3,6-di-O-benzyl-2-deoxy-α- -gluco-
pyranosyl)-(1Ǟ4)-O-(Methyl 3-O-Benzyl-2-O-pivaloyl-α- -idopyr-
anosyluronate)-(1 Ǟ4)-2-acetamido-6-O-benzoyl-3-O-benzyl-2-de-
oxy-α- -glucopyranoside (3): TMSOTf (150 μL of a 0.17 m solution
L-idopyranosyl-
D
D-
L
L
D
D
copyranoside (21): EtSH (48 μL, 0.65 mmol) and catalytic pTsOH
were added to a solution of 20 (250 mg, 0.13 mmol) in dry CH2Cl2
(4 mL). After stirring for 2 h under argon, the mixture was neutral-
ized with solid NaHCO3, diluted with CH2Cl2 (75 mL), washed
with H2O (50 mL), dried (MgSO4) and concentrated to dryness.
The purification of the residue was carried out by flash chromatog-
raphy (1:2 hexane/AcOEt) to yield 21 (201 mg, 84%). [α]2D0 = +35.0
(c = 0.5, CHCl3); TLC (1:2 hexane/AcOEt), Rf = 0.51. H NMR
(500 MHz, CDCl3): δ = 8.07–7.17 (m, 40 H, Ph), 5.46 (d, J1,2
6.5 Hz, 1 H, 1D-H), 5.39 (d, J1,2 = 5.0 Hz, 1 H, 1B-H), 5.27 (d,
L
D
in dry CH2Cl2) was added at room temperature, under argon, to a
solution of 22 (178 mg, 92 μmol) and 4 (105 mg, 0.166 mmol) in
dry CH2Cl2 (2 mL). After 3 h, saturated NaHCO3 solution (2 mL)
and CH2Cl2 (50 mL) were added and the mixture was washed with
H2O (35 mL). The organic layer was dried (MgSO4) and concen-
trated in vacuo, and the residue was purified by flash column
chromatography (3:1 toluene/AcOEt) to yield 3 (115 mg, 52%) and
1
=
JNH,2 = 9.0 Hz, 1 H, NHCOCH3), 5.19 (d, 1 H, 1E-H), 5.02 (m, 2 unreacted acceptor (79 mg, 44%). [α]2D0 = +24.7 (c = 0.7, CHCl3);
H, 2B-H, 1C-H), 4.92–4.43 (m, 19 H, 1A-H, 5B-H, 5D-H, 6A-H, TLC (3:1 toluene/AcOEt), Rf = = 0.35. 1H NMR (500 MHz,
6ЈA-H, CH2Ph), 4.21 (m, 1 H, 2A-H), 4.10–3.98 (m, 7 H), 3.81– CDCl3): δ = 8.06–7.09 (m, 60 H, Ph), 5.58 (d, J1,2 = 6.0 Hz, 1 H,
3.62 (m, 10 H), 3.50 (s, 3 H, COOCH3), 3.49 (m, 1 H), 3.38 (dd, 1
H, 2D-H), 3.32 (m,1 H, 2C-H), 3.26 (s, 3 H, COOCH3), 3.16 (m,
1 H, 2E-H), 3.00 (br. s, 1 H, OH), 2.31 (br. s, 1 H, OH), 1.80 (s, 3
1F-H), 5.40 (d, J1,2 = 7.0 Hz, 1 H, 1D-H), 5.38 (d, J1,2 = 5.5 Hz,
1 H, 1B-H), 5.27–5.20 (m, 2 H, NHCOCH3, 2F-H), 5.12 (d, J1,2
3.5 Hz, 1 H, 1E-H), 5.03–5.00 (m, 2 H, 2B-H, 1C-H), 4.96–4.41
=
H, NHCOCH3), 1.19 (s, 9 H, OCOC(CH3)3), 1.19–1.07 (2d, 6 H, (m, 25 H, 1A-H, 6A-H, 6ЈA-H, 5B-H, 5F-H, 6E-H, 6ЈE-H,
J = 6.0 Hz, CH(CH3)2) ppm. 13C NMR (125 MHz, CDCl3): δ = CH2Ph), 4.21–4.18 (m, 2 H, 5D-H, 2A-H), 4.14 (dd, J3,4 = J4,5
177.4, 169.9, 169.6, 169.4, 166.2, 138.7–127.7 (Ph), 100.0, 99.1, 9.2 Hz, 1 H, 4E-H), 4.09–3.93 (m, 7 H, 4A-H, 5A-H, 3B-H, 4B-H,
98.2, 97.7, 95.7, 81.2, 79.1, 78.9, 78.4, 76.2, 76.1, 75.6, 75.0, 74.9, 4C-H, 3D-H, 3F-H), 3.90–3.77 (m, 5 H, CH(CH3)2, 5C-H, 4D-H,
74.8, 74.61, 74.57, 73.9, 73.5, 72.3, 72.2, 71.6, 71.2, 71.0, 70.9, 70.4, 5E-H, 4F-H), 3.73–3.59 (m, 4 H, 3A-H, 3C-H, 3E-H, 6C-H), 3.46
=
62.8, 62.7, 61.8, 52.2, 51.9, 51.7, 38.9, 27.1, 23.3, 23.2, 21.6 ppm.
C98H113N7O28·H2O (1855.0): C 63.45, H 6.25, N 5.29; found C
63.52, H 6.31, N 5.28.
(m, 1 H, 6ЈC-H), 3.41–3.40 (2s, 6 H, COOCH3), 3.36–3.29 (m, 3
H, 2C-H, 2D-H, 2E-H), 3.24 (s, 3 H, COOCH3), 1.80 (s, 3 H,
NHCOCH3), 1.18 (s, 9 H, OCOC(CH3)3), 1.18–1.07 (2d, J =
6.0 Hz, 6 H, CH(CH3)2) ppm. 13C NMR (125 MHz, CDCl3): δ =
178.0, 170.4, 170.3, 170.06, 170.03, 166.77, 166.68, 165.9, 139.3–
128.5 (Ph), 100.6, 99.5, 98.8, 98.7, 98.3, 96.4, 82.2, 79.6, 79.0, 78.6,
78.5, 76.92, 76.89, 76.5, 76.44, 76.37, 76.2, 76.1, 75.73, 75.68, 75.4,
75.2, 74.5, 74.3, 74.0, 73.6, 73.0, 72.4, 72.20, 72.16, 71.9, 71.7, 71.0,
70.6, 70.1, 67.8, 63.5, 63.4, 62.5, 52.8, 52.27, 52.23, 39.5, 30.3, 27.7,
24.0, 23.8, 22.2 ppm. C133H143N7O36 (2415.7): C 66.13, H 5.97, N
4.06; found C 66.06, H 5.88, N 4.34.
Isopropyl O-(2-Azido-6-O-benzoyl-3-O-benzyl-2-deoxy-α-
ranosyl)-(1Ǟ4)-O-(Methyl 2,3-Di-O-benzyl-α- -idopyranosyluron-
ate)-(1Ǟ4)-O-(2-Azido-3,6-di-O-benzyl-2-deoxy-α- -glucopyranos-
yl)-(1Ǟ4)-O-(Methyl 3-O-Benzyl-2-O-pivaloyl-α- -idopyranosyl-
uronate)-(1Ǟ4)-2-acetamido-6-O-benzoyl-3-O-benzyl-2-deoxy-α-
D-glucopy-
L
D
L
D-
glucopyranoside (22): BzCN (100 μL of a 1.1 m solution in dry
CH3CN) and catalytic Et3N were added to a cooled (–40 °C) solu-
tion of 21 (190 mg, 103 μmol) in dry CH3CN (3 mL). After 30 min,
additional BzCN was added (20 μL of a 1.1 m solution in dry
CH3CN) until starting material disappeared. After 1 h, MeOH was
added and the mixture was allowed to reach room temperature.
The solvent was evaporated and the residue was dissolved in
MeOH and concentrated to dryness. The purification was carried
out by flash chromatography (75:1 CH2Cl2/MeOH) to afford 22
(198 mg, 99%). [α]2D0 = +33.4 (c = 0.6, CHCl3); TLC (75:1 CH2Cl2/
Isopropyl O-(3,4-Di-O-benzyl-α-
O-(2-Azido-3-O-benzyl-2-deoxy-α-
(2,3-Di-O-benzyl-α- -idopyranosyluronic Acid)-(1Ǟ4)-O-(2-Azido-
3,6-di-O-benzyl-2-deoxy-α- -glucopyranosyl)-(1Ǟ4)-O-(3-O-Ben-
zyl-α- -idopyranosyluronic Acid)-(1Ǟ4)-2-acetamido-3-O-benzyl-2-
deoxy-α- -glucopyranoside (23): H2O2 (30%, 0.55 mL) and LiOH
solution (1 n, 0.9 mL) were added to a solution of 3 (33 mg,
L-idopyranosyluronic Acid)-(1Ǟ4)-
D
-glucopyranosyl)-(1 Ǟ 4)-O-
L
D
L
D
MeOH), Rf = 0.28. 1H NMR (500 MHz, CDCl3): δ = 8.10–7.17 14 μmol) in THF (1.6 mL) at –5 °C. After stirring for 24 h at room
(m, 45 H, Ph), 5.48 (d, J1,2 = 6.4 Hz, 1 H, 1D-H), 5.41 (d, J1,2
=
temperature, the mixture was cooled to 0 °C and MeOH (2.8 mL)
5.3 Hz, 1 H, 1B-H), 5.30 (d, JNH,2 = 9.1 Hz, 1 H, NHCOCH3),
and KOH solution (3 n, 1.6 mL) were added. After stirring for 24 h
5.24 (d, 1 H, 1E-H), 5.07–5.03 (m, 2 H, 2B-H, 1C-H), 4.93–4.65 at room temperature, the reaction mixture was neutralized with IR-
(m, 15 H, 1A-H, 6A-H, 5B-H, 6E-H, CH2Ph), 4.61–4.46 (m, 5 H,
120-H+ Amberlite resin and was then filtered and concentrated.
1856
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 1849–1858