J. Jiménez-Barbero, C. Vicent et al.
FULL PAPER
1-H), 5.02–5.28 (m, 2 H), 4.85 (m, 1 H), 3.79 (m, 5-H), 3.83 (s, 3
7), 7.49 (d, J = 9.2 Hz, 1 H, 5-NH), 7.64 (dd, J = 8.0, 0.9 Hz, 1 H,
H, CH3), 3.74 (s, 3 H, CH3), 3.22 (m, 2 H,CH2-γ), 2.26 (m, 2 H, Ind-4), 8.11 (t, J = 5.7 Hz, 1 H, 3-NH), 9.83 (s, 1 H, 4-NH), 10.29
CH2-γ), 2.16 (s, 3 H, CH3), 2.05 (s, 3 H, CH3), 1.91 (s, 3 H, CH3), (s, 1 H, 2-NH), 11.61 (d, J = 2.2 Hz, 1-NH) ppm. 13C NMR
1.77 (m, 2 H,CH2-γ), 1.12 (d, J = 6.3 Hz, CH3) ppm. 13C NMR (125 MHz, [D6]DMSO): δ = 25.6 (CH2, γ-b), 33.3 (CH2, γ-c), 36.0
(75 MHz, [D6]DMSO): δ = 171 (CO), 170.5 (CO), 170.1 (CO), 170 (CH3, MeA), 36.1 (CH3, MeB), 38.22 (CH2, γ-a), 61.2 (CH, C-6),
(CO), 162.4 (CONH), 160.6 (CONH), 159.2 (CONH), 136.6 66.6 (CH, C-4), 70.6 (CH, C-2), 73.9 (CH, C-3), 77.1 (CH, C-1),
(CONH), 130.9 (C), 127.7 (C), 124.7 (C), 123.4 (C), 122.1 (C), 78.9 (CH, C-5), 102.8 (CH, Ind-3), 103.7 (CH, Py-3B), 104.0 (CH,
121.8 (C), 121.7 (C), 120.9 (C), 120.8 (C), 120.35 (C), 119.4 (C),
112.0 (C), 104.7 (C), 104.4 (C), 103.06 (C), 103.0 (C), 76.2 (CH),
Py-3A), 112.2 (CH, Ind-7), 118.1 (CH, Py-5A), 118.7 (CH, Py-5B),
119.8 (CH, Ind-5), 121.5 (CH, Ind-4), 121.5 (C, Py-4B), 121.6 (C,
73.34 (CH), 71.7 (CH), 70.7 (CH), 70.3 (CH), 38.6 (CH2), 36.6 Py-2B), 122.2 (C, Py-4A), 123.1 (C, Py-2A), 123.3 (CH, Ind-6),
(CH2), 34.04 (CH2), 33.41 (CH2), 25.77 (CH2), 20.9 (CH3CO), 20.8 127.0 (C, Ind-3a), 131.6 (C, Ind-2), 136.5 (C, Ind-7a), 158.2 (CO),
(CH3CO), 20.62 (CH3CO), 17.5 (CH3) ppm. MS (ES+): m/z (%) = 159.9 (CO), 161.2 (CO), 169.3 (CO) ppm. HRMS (ESI+) calcd. for
685 (10) [M + Na]+, 762 (100) [M + H]+. IR (KBr): ν = 3422, 2934, C31H37N7O9 [M + H]+ 651.2726; found 652.2732. IR (KBr): ν =
˜
˜
3414, 1643, 1591, 1520, 1465, 1438, 1404, 1341, 1307, 1252, 1207,
1146, 1075, 750, 549 cm–1. C31H37N7O9 (651.67): calcd. C 57.14, H
5.72, N 15.05; found C 57.45, H 5.50, N 15.23.
1750, 1646, 1514, 1438, 1402, 1370 cm–1.
β- -Man-Py-γ-Py-Ind (1): A solution of 17 (171 mg, 0.21 mmol)
D
in MeOH (6 mL) was treated with a solution of NaOMe (45 mg,
0.83 mmol) in MeOH (1 mL). This resulted in an immediate deeper
yellow colour that indicated that the reaction was complete. The
solution was acidified to pH 6 with Amberlite IR-120 ion-exchange
resin. The resin was removed by filtration, and the solvent was
evaporated. The residue was purified by column chromatography
(CH2Cl2/MeOH/toluene, 5:2:1) to give 1 (108 mg, 79%). Rf = 0.12
(CH2Cl2/MeOH/H2O, 6:1:0.1), m.p. 187–190 °C. [α]D = + 9.61 (c =
0.77, MeOH). 1H NMR (500 MHz, [D6]DMSO): δ = 1.76–1.82 (m,
2 H, γ-b), 2.27 (t, J = 7.5 Hz, 2 H, γ-c), 3.10 (ddd, J = 9.3, 6.0,
2.2 Hz, m, 1 H, 5-H), 3.22 (q, J = 6.6 Hz, 2 H, γ-a), 3.33–3.45 (m,
3 H, 3-H, 4-H, 6-H), 3.63–3.66 (m, 1 H, 2-H), 3.65–3.68 (m, 1 H,
6Ј-H), 3.79 (s, 3 H, MeA), 3.84 (s, 3 H, MeB), 4.46 (t, J = 5.9 Hz,
1 H, 6-OH), 4.73 (t, J = 5.48 Hz, 2 H, 3-OH, 4-OH), 5.10 (d, J =
4.4 Hz, 1 H, 2-OH), 5.13 (d, J = 9.3 Hz, 1-H), 6.69 (d, J = 1.9 Hz,
1 H, Py-3B), 6.89 (d, J = 1.9 Hz, Py-3A), 7.05 (ddd, J = 8.0, 6.9,
1.0 Hz, 1 H, Ind-5), 7.17–7.21 (m, 2 H, Ind-6, P-5B), 7.28 (m, 2 H,
Ind-3, Py-5A), 7.46 (d, J = 9.2 Hz, 1 H, Ind-7), 7.49 (d, J = 9.2 Hz,
1 H, 5-NH), 7.64 (dd, J = 8.0, 0.9 Hz, 1 H, Ind-4), 8.11 (t, J =
5.7 Hz, 1 H, 3-NH), 9.83 (s, 1 H, 4-NH), 10.29 (s, 1 H, 2-NH),
11.61 (d, J = 2.2 Hz, 1-NH) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 25.6 (CH2, γ-b), 33.3 (CH2, γ-c), 36.0 (CH3, MeA),
36.1 (CH3, MeB), 38.22 (CH2, γ-a), 61.2 (CH, C-6), 66.6 (CH, C-
4), 70.6 (CH, C-2), 73.9 (CH, C-3), 77.1 (CH, C-1), 78.9 (CH, C-
5), 102.8 (CH, Ind-3), 103.7 (CH, Py-3B), 104.0 (CH, Py-3A), 112.2
(CH, Ind-7), 118.1 (CH, Py-5A), 118.7 (CH, Py-5B), 119.8 (CH,
Ind-5), 121.5 (CH, Ind-4), 121.5 (C, Py-4B), 121.6 (C, Py-2B), 122.2
(C, Py-4A), 123.1 (C, Py-2A), 123.3 (CH, Ind-6), 127.0 (C, Ind-3a),
131.6 (C, Ind-2), 136.5 (C, Ind-7a), 158.2 (CO), 159.9 (CO), 161.2
(CO), 169.3 (CO) ppm. HRMS (ESI+): calcd. for C31H38N7O9 [M
6-Deoxy-β-D-Man-Py-γ-Py-Ind (3): Compound 3 was prepared
from 19 (0.3 g, 0.42 mmol) as described above for the synthesis of
compound 1. The residue was purified by column chromatography
(SiO2; CH2Cl2/MeOH/H2O, 6:1:0.1) to give compound 3 (108 mg,
79%). Rf = 0.24 (CH2Cl2/MeOH/H2O, 6:1:0.1), m.p. 175–180 °C.
[α]D = –23.2 (c = 0.97, MeOH). 1H NMR (500 MHz, [D6]DMSO):
δ = 1.14 (d, J = 5.5 Hz, 3 H), 1.75–1.83 (m, 2 H, γ-b), 2.28 (t, J =
7.5 Hz, 2 H, γ-c), 3.12–3.17 (m, 2 H, 4-H, 5-H), 3.20–3.25 (m, 2
H, γ-a), 3.3 (m, 1 H, 3-H), 3.61–3.67 (m, 1 H, 2-H), 3.79 (s, 3 H,
MeB), 3.84 (s, 3 H, MeA), 4.70 (d, J = 5.9 Hz, 1 H, 3-OH), 4.77
(d, J = 5.0 Hz, 1 H, 4-OH), 5.09 (d, J = 4.7 Hz, 2 H, 1-H, 2-OH),
6.69 (d, J = 1.9 Hz, 1 H, Py-3B), 6.89 (d, J = 1.9 Hz, 1 H, Py-3A),
7.05 (ddd, J = 8.0, 7.0, 1.0 Hz, 1 H, Ind-5), 7.14–7.23 (m, 2 H, Ind-
6, Py-5B), 7.28 (t, J = 2.1 Hz, 2 H, Ind-3, Py-5A), 7.45–7.48 (m, 2
H, 5-NH, Ind-7), 7.65 (m, 1 H, Ind-4), 8.10 (t, J = 5.7 Hz, 1 H, 3-
NH), 9.82 (s, 1 H, 4-NH), 10.28 (s, 1 H, 2-NH), 11.60 (d, J =
2.2 Hz, 1 H, 1-NH) ppm. 13C NMR (125 MHz, [D6]DMSO): δ =
17.97 (CH3, Me), 25.62 (CH2, γ-b), 33.27 (CH2, γ-c), 36.06 (CH3,
MeA), 36.12 (CH3, MeB), 38.18 (CH2, γ-a), 70.82 (CH, C-2), 71.73
(CH, C-4), 73.48 (CH, C-5), 73.72 (CH, C-3), 77.15 (CH, C-1),
102.80 (CH, Ind-3), 103.89 (CH, Py-3B), 104.08 (CH, Py-3A),
112.29 (CH, Ind-7), 118.09 (CH, Py-5A), 118.76 (CH, Py-5B),
119.77 (CH, Ind-5), 121.52 (CH, Py-4A), 121.62 (CH, Ind-4),
121.71 (CH, Py-2B), 122.24 (CH, Py-4B), 123.22 (CH, Py-2A),
123.36 (CH, Ind-6), 127.12 (C, Ind-3a), 131.65 (C, Ind-2), 136.57
(C, Ind-7a), 158.19 (CO), 160.03 (CO), 161.19 (CO), 169.25 (CO)
ppm. HRMS (ESI+) calcd. for C31H37N7O8 [M + H]+ 636.2776;
found 636.2771. IR (KBr): ν = 3429, 2930, 1640, 1591, 1518, 1645,
˜
1438, 1403, 1341, 1307, 1250, 1146, 1067, 1014, 892, 748, 576 cm–1.
C31H37N7O8 (635.68): calcd. C 58.57, H 5.87, N 15.42; found C
58.49, H 5.79, N 15.62.
+ H]+ 652.2726; found 652.2726. IR (KBr): ν = 3412, 2930, 2935,
˜
1642, 1589, 1519 cm–1. C31H37N7O9 (651.67): calcd. C 57.14, H
5.72, N 15.05; found C 57.19, H 5.90, N 15.49.
Sample Preparation for NMR Experiments: Calf thymus DNA (ct-
DNA) and poly(dA-dT)2 were purchased from Sigma–Aldrich, and
were used without further purification.
β-L-Man-Py-γ-Py-Ind (2): Compound 2 was prepared from 18
(40 mg, 0.05 mmol) as described above for the synthesis of com-
pound 1. The residue was purified by column chromatography
(CH2Cl2/MeOH/H2O, 6:1:0.1) to give compound 2 (22 mg, 70%).
1H NMR Spectroscopy: All spectra in aqueous solution were re-
corded with presaturation of the water signal. Chemical shifts are
reported in ppm relative to [D4](trimethylsilyl)propionic acid (δ =
0.00 ppm) when D2O at 25 °C and H2O at 5 °C was used in the
experiment. NMR structural studies of compounds 1–3 in the free
state were based on one-dimensional and two-dimensional
(TOCSY, HSQC, NOESY, ROESY) experiments recorded at
500 MHz with a Bruker Avance spectrometer. Sample solutions
were prepared at concentrations in the range 10–4–10–3 m depending
on the solubility of the compounds.
Rf = 0.12 (CH2Cl2/MeOH/H2O, 6:1:0.1), m.p. 150–155 °C. [α]D
=
–10.7 (c = 0.8, MeOH). 1H NMR (500 MHz, [D6]DMSO): δ =
1.76–1.82 (m, 2 H, γ-b), 2.27 (t, J = 7.5 Hz, 2 H, γ-c), 3.10 (ddd,
J = 9.3, 6.0, 2.2 Hz, m, 1 H, 5-H), 3.22 (q, J = 6.6 Hz, 2 H, γ-a),
3.33–3.45 (m, 3 H, 3-H, 4-H, 6-H), 3.63–3.66 (m, 1 H, 2-H), 3.65–
3.68 (m, 1 H, 6Ј-H), 3.79 (s, 3 H, MeA), 3.84 (s, 3 H, MeB), 4.46
(t, J = 5.9 Hz, 1 H, 6-OH), 4.73 (t, J = 5.48 Hz, 2 H, 3-OH, 4-
OH), 5.10 (d, J = 4.4 Hz, 1 H, 2-OH), 5.13 (d, J = 9.3 Hz, 1-H),
6.69 (d, J = 1.9 Hz, 1 H, Py-3B), 6.89 (d, J = 1.9 Hz, Py-3A), 7.05
(ddd, J = 8.0, 6.9, 1.0 Hz, 1 H, Ind-5), 7.17–7.21 (m, 2 H, Ind-6,
Bound-State NMR Spectroscopic Experiments (TR-NOESY and
P-5B), 7.28 (m, 2 H, Ind-3, Py-5A), 7.46 (d, J = 9.2 Hz, 1 H, Ind- Differential Frequency STD Experiments): These experiments were
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Eur. J. Org. Chem. 2015, 6180–6193