C. Carpenter, S. A. Nepogodiev
H, H-6Јa), 3.96 (m, 1 H, H-5Ј), 4.03–4.17 (m, 3 H, H-5, H-6a, H- (dd, J1,2 = 2.0, J1,OH = 4.3 Hz, 1 H, H-1), 5.43 (dd, J2,3 = 3.2, J3,4
FULL PAPER
6Јb), 4.20 (dd, J5,6a = 3.5, J6a,6b = 12.0 Hz, 1 H, H-6b), 4.30 (dd,
J2,3 = 2.2, J3,4 = 9.8 Hz, 1 H, H-3), 4.99–5.03 (m, 2 H, H-1Ј, H-
2Ј), 5.08 (dd, J2,3 = 3.2, J3,4 = 10.0 Hz, 1 H, H-3Ј), 5.18 (dd, J3,4
= 10.0 Hz, 1 H, H-3), 5.48 (dd, J1,2 = 1.8, J2,3 = 3.2 Hz, 1 H, H-
2Ј), 5.55 (dd, J3,4 Ϸ J4,5 Ϸ 9.8 Hz, 1 H, H-4Ј), 7.55 (m, 2 H, Ph),
7.65 (m, 1 H, Ph), 8.12 (m, 1 H, Ph) ppm. 13C NMR (100 MHz,
Ϸ J4,5 Ϸ 10.0 Hz, 1 H, H-4Ј), 5.41 (d, J1,2 = 1.5 Hz, 1 H, H-1), CDCl3): δ = 21.0–21.2 (CH3CO), 62.1 (C-6ЈЈ), 62.8, 63.1 (C-6, C-
5.53–5.59 (dd, J3,4 Ϸ J4,5 Ϸ 9.8 Hz, 1 H, H-4), 7.50 (m, 1 H, Ph), 6Ј), 65.8 (C-4ЈЈ), 66.8 (C-4), 67.2 (C-4Ј), 68.7, 69.1, 69.7, 69.9 (×2)
7.64 (m, 2 H, Ph), 8.12 (m, 2 H, Ph), 8.78 (s, 1 H, NH) ppm. 13C (C-5, C-5Ј, C-2ЈЈ, C-3ЈЈ, C5ЈЈ), 70.3 (C-3), 71.8 (C-2Ј), 76.9 (C-3Ј),
NMR (100 MHz, D2O): δ = 20.8, 20.9, 21.1 (×6, CH3CO), 62.25
(C-6, C-6Ј), 65.8 (C-4Ј), 66.7 (C-4), 68.7, (C-3Ј), 69.8, 69.9 (C-2Ј,
78.0 (C-2), 93.2 (C-1), 99.2 (C-1Ј), 99.6 (C-1ЈЈ), 129.1, 129.4, 130.3,
134.2 (Ph), 165.9–171.2 (C=O) ppm. HR ESI-MS: calcd. for
C-5Ј), 70.3 (C-2), 71.6 (C-5), 76.1 (C-3), 90.9 (C-1), 99.6 (C-1Ј), C43H54O26 ([M + NH]+): m/z = 1004.3242, found: m/z = 1004.3247.
129.0, 129.3, 130.3, 134.2 (Ph), 159.7–170.7 (×8, C=O) ppm.
LSIMS: m/z
C33H38Cl3NO18 (841.12).
3,4,6-Tri-O-acetyl-2-O-[4,6-di-O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-
= 684 [M +
Na]+, 681 [M–OC(NH)CCl3]+.
α-
D
-mannopyranosyl)-2-O-benzoyl-α-
D-mannopyranosyl]-1-O-tri-
chloroacetimidoyl-α-
D-mannopyranose (25): A mixture of hemiace-
1,3,4,6-Tetra-O-acetyl-2-O-[4,6-di-O-acetyl-3-O-(2,3,4,6-tetra-O-
acetyl-α- -mannopyranosyl)-2-O-benzoyl-α- -mannopyranosyl]-β-
-mannopyranose (23): mixture of imidate 21 (5.38 g,
tal 24 (2.60 g, 2.63 mmol), Cl3CCN (1.18 mL, 11.8 mmol) and
powdered K2CO3 (1.18 g) in CH2Cl2 (25 mL) was stirred at room
temperature for 2 h, diluted with CH2Cl2 (75 mL) and K2CO3 was
then removed by filtration. The filtrate was concentrated and the
residue was purified by short-column chromatography (toluene/
EtOAc/Et3N, 50:50:1) to give imidate 25 (2.66 g, 89%). Rf = 0.39
(toluene/EtOAc, 1:1). [α]D = +5 (c = 1.1, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 1.93, 1.98, 2.07, 2.09 (×2), 2.10, 2.13, 2.17,
D
D
D
A
6.38 mmol), alcohol 22[51] (2.44 g, 7.00 mmol) and powdered mol.
sieves (4 Å, 6.5 g) in CH2Cl2 (60 mL) was stirred for 30 min under
N2 and cooled to 0 °C. To this mixture a solution of BF3·OEt2
(0.19 mL, 1.60 mmol) in CH2Cl2 (5 mL) was added via a syringe
and, after stirring for 30 min at 0–10 °C, TLC indicated no presence
of starting material. The reaction mixture was treated with Et3N
(0.5 mL) and filtered, the filtrate was diluted with CH2Cl2 (100 mL)
and washed successively with saturated aq. NaHCO3 and water.
After removal of solvents in vacuo the residue was purified by col-
umn chromatography (toluene/EtOAc, 4:1Ǟ1:1) to afford the tri-
saccharide 23 (3.61 g, 55%). Rf = 0.45 (toluene/EtOAc, 2:3). [α]D
= –16 (c = 1.4, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.93,
2.18, 2.21, (9 s, 27 H, CH3CO), 3.82 (dd, J5,6a = 2.5, J6a,6b
=
12.3 Hz, 1 H, H-6ЈЈa), 3.96 (m, 1 H, H-5ЈЈ), 4.06 (dd, J5,6a = 4.0,
J6a,6b = 12.3 Hz, 1 H, H-6ЈЈb), 4.17–4.30 (m, 6 H, H-5, H-6a, H-
6b, H-5Ј, H-6Јa, H-6Јb), 4.30–4.35 (m, 2 H, H-2, H-3Ј), 5.12 (d,
J1,2 = 1.7 Hz, 1 H, H-1ЈЈ), 5.14–5.20 (m, 2 H, H-2ЈЈ, H-3ЈЈ), 5.22
(d, J1,2 = 1.8 Hz, 1 H, H-1Ј), 5.28 (dd, J3,4 Ϸ J4,5 Ϸ 9.8 Hz, 1 H,
H4ЈЈ), 5.40 (dd, J2,3 = 3.0, J3,4 = 9.8 Hz, 1 H, H-3), 5.45 (dd, J3,4
1.98, 2.08, 2.09, 2.11, 2.12, 2.17, 2.19, 2.21, 2.22 (10 s, 30 H, Ϸ J4,5 Ϸ 9.8 Hz, 1 H, H-4), 5.49 (dd, J1,2 = 1.8, J2,3 = 3.2 Hz, 1
CH3CO), 3.84 (m, 1 H, H-5), 3.89 (dd, J5,6a = 2.3, J6a,6b = 12.5 Hz, H, H-2Ј), 5.56 (dd, J3,4 Ϸ J4,5 Ϸ 9.8 Hz, 1 H, H-4Ј), 6.45 (d, J1,2
=
1 H, H-6ЈЈa), 3.97 (m, 1 H, H-5ЈЈ), 4.07–4.19 (m, 3 H, H-6a, H- 2.0 Hz, 1 H, H-1), 7.52 (m, 2 H, Ph), 7.65 (m, 1 H, Ph), 8.12 (m,
6Јa, H-6ЈЈb), 4.22 (broad d, 1 H, H-2), 4.30 (dd, J5,6a = 5.5, J6a,6b
= 12.3 Hz, 1 H, H-6b), 4.34 (dd, J5,6a = 4.2, J6a,6b = 11.3 Hz, 1 H,
H-6ЈЈb), 4.41 (dd, J2,3 = 3.0, J3,4 = 10.0 Hz, 1 H, H-3Ј), 4.47 (m, 1
1 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.0- 21.3
(CH3CO), 62.1(C-6ЈЈ), 62.5, 62.7 (C-6, C-6Ј), 65.8, 65.9 (C-4, C-
4ЈЈ), 67.0 (C-4Ј), 69.1, 69.9 (×2), 70.2 (×2) (C-3, C-2ЈЈ, C-3ЈЈ, C-
H, H-5Ј), 5.10 (broad s, 1 H, H-1ЈЈ), 5.14–5.22 (m, 3 H, H-3, H- 5ЈЈ, C-5 or C-5Ј), 71.6, 71.7 (C-3Ј, C-5 or C-5Ј), 75.5 (C-2), 76.9
2ЈЈ, H-3ЈЈ), 5.24 (d, J1,2 = 1.8 Hz, 1 H, H-1Ј), 5.28 (dd, J3,4 Ϸ J4,5
Ϸ 10.0 Hz, 1 H, H4ЈЈ), 5.32 (dd, J1,2 Ϸ J2,3 Ϸ 9.8 Hz, 1 H, H-4),
5.52 (broad d, 1 H, H-2Ј), 5.65 (dd, J3,4 Ϸ J4,5 = 9.8 Hz, 1 H, H-
4Ј), 5.82 (broad s, 1 H, H-1), 7.53 (m, 2 H, Ph), 7.65 (m, 1 H, Ph),
8.13 (m, 1 H, Ph) ppm. 13C NMR (100 MHz, CDCl3): δ = 20.8–
21.3 (CH3CO), 60.7 (C-6ЈЈ), 62.1 (C-6), 62.5 (C-6Ј), 65.7, 66.2, 66.8
(C-4, C-4Ј, C-4ЈЈ), 69.0, 69.4, 69.7, 69.9 (C5Ј, C-2ЈЈ, C-3ЈЈ, C-5ЈЈ),
71.7 (C-5), 72.5 (C-2Ј), 73.5 (C-3), 75 (C-2), 76.9 (C-3Ј), 91.4 (C-
1), 98.4 (C-1Ј), 99.6 (C-1ЈЈ), 129.0, 129.4, 130.2, 134.1 (Ph), 165.7–
170.9 (×10, C=O) ppm. HR ESI-MS: calcd. for C45H56O27 ([M +
NH4]+): m/z = 1046.3347, found: m/z = 1046.3326.
(C-3), 95.9 (C-1), 99.4, 99.6 (C-1Ј, C-1ЈЈ), 129.2, 129.4, 130.3, 134.3
(Ph), 160.4–170.9 (C=O) ppm. HR ESI-MS: calcd. for
C45H58Cl3N2O26 ([M + NH4]+): m/z = 1147.2338, found: m/z =
1147.2322.
3-[(Benzyloxycarbonyl)amino]propyl 3,4,6-Tri-O-acetyl-2-O-[4,6-di-
O-acetyl-3-O-(2,3,4,6-tetra-O-acetyl-α-
D-mannopyranosyl)-2-O-ben-
zoyl-α- -mannopyranosyl]-α- -mannopyranoside (26): A mixture of
D
D
the imidate 25 (1.65 g, 1.46 mmol), alcohol 2 (600 mg, 2.87 mmol)
and powdered mol. sieves (4 Å, 0.5 g) in CH2Cl2 (30 mL) was
stirred for 30 min under N2 and then cooled to 0 °C. To this mix-
ture a solution of TMSOTf (30 μL, 0.15 mmol) in CH2Cl2 (5 mL)
was added via a syringe and the mixture was stirred for 1.5 h to
allow the temperature to rise gradually to 10 °C before addition of
Et3N (0.1 mL). The mixture was filtered through Celite, the filtrate
was diluted with CH2Cl2 (100 mL) and washed successively with
saturated aq. NaHCO3 and water. Solvents were evaporated in
vacuo to give crude product which was purified by column
chromatography (toluene/Me2CO, 4:1) to afford the trisaccharide
26 (1.56 g, 91%). Rf = 0.32 (toluene/EtOAc, 1:1). [α]D = –1 (c =
1.0, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 1.83 (m, 2 H,
3,4,6-Tetra-O-acetyl-2-O-[4,6-di-O-acetyl-3-O-(2,3,4,6-tetra-O-ace-
tyl-α-D-mannopyranosyl)-α-D-mannopyranosyl]-2-O-benzoyl-α-D-
mannopyranose (24): A solution of the trisaccharide 23 (3.44 g,
3.34 mmol) and NH2NH2·HOAc (305 mg, 3.34 mmol) in DMF
(30 mL) was stirred for 2 h at room temperature, diluted with
EtOAc (200 mL), washed with water (3×75 mL) and the organic
layer was dried and concentrated. Column chromatography (tolu-
ene/EtOAc, 1:1) afforded the hemiacetal 24 (2.80 g, 85%). Rf =
1
0.43 (toluene/EtOAc, 3:7). [α]D = –10 (c = 1.2, CHCl3). H NMR
(400 MHz, CDCl3): δ = 1.93, 1.98, 2.08, 2.09, 2.11, 2.14, 2.17 (×2), CH2CH2CH2), 1.94, 1.95, 2.04, 2.06 (×2), 2.09, 2.14 (×2), 2.18 (9
2.21, (9 s, 27 H, CH3CO), 3.40 (broad s, 1 H, OH), 3.86 (dd, J5,6a
= 2.3, J6a,6b = 12.3 Hz, 1 H, H-6ЈЈa), 3.96 (m, 1 H, H-5ЈЈ), 4.07
s, 27 H, CH3CO), 3.30 (m, 2 H, CH2N), 3.51 (m, 1 H, OCH-
aHbCH2), 3.79 (m, 1 H, OCHaHbCH2), 3.82 (dd, J5,6a = 2.4, J6a,6b
(dd, J5,6a = 4.0, J6a,6b = 12.3 Hz, 1 H, H-6ЈЈb), 4.13 (m, 1 H, H-2), = 12.4 Hz, 1 H, H-6ЈЈa), 3.91–3.99 (m, 2 H, H-5, H-5ЈЈ), 4.04 (dd,
4.14–4.27 (m, 6 H, H-5, H-6a, H-6b, H-5Ј, H-6Јa, H-6Јb), 4.32 (dd, J5,6b = 4.0, J6a,6b = 12.4 Hz, 1 H, H-6ЈЈb), 4.07 (broad d, J = 3 Hz,
J2,3 = 3.3, J3,4 = 9.8 Hz, 1 H, H-3Ј), 5.10 (d, J1,2 = 2.0 Hz, 1 H, H-
1ЈЈ), 5.14–5.20 (m, 3 H, H-1Ј, H-2ЈЈ, H-3ЈЈ), 5.28 (dd, J3,4 Ϸ J4,5
9.8 Hz, 1 H, H4ЈЈ), 5.32 (dd, J3,4 Ϸ J4,5 Ϸ 9.6 Hz, 1 H, H-4), 5.39
1 H, H-2), 4.10–4.18 (m, 2 H, H-6a, H-5Ј), 4.18–4.26 (m, 2 H, H-
6b, H-6Јa, H-6Јb), 4.29 (dd, J2.3 = 3.2, J3,4 = 9.7 Hz, 1 H, H-3Ј),
4.95 (broad s, 1 H, H-1), 5.08 (broad s, 3 H, H-1ЈЈ, CH2Ph), 5.10–
Ϸ
3294
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 3286–3296