Glycoconjugated Azodyes
8Ј-H, 12Ј-H), 7.41 (m, 3 H, 3Ј-H, 4Ј-H, 5Ј-H), 6.73 (m, 2 H, 9Ј-H, CH), 111.8, 109.3 [2ϫC(CH3)2], 71.5, 70.5, 68.4 (3ϫCH2O), 50.4,
11Ј-H), 3.56–3.40 (m, 10 H, 2ϫCH2N, 3 ϫCH2O), 1.58 [m, 6 H,
(CH2)3], 1.49, 1.42, 1.34, 1.30 [4ϫs, each 3 H, 2ϫC(CH3)2], 1.20
46.0 (2ϫCH2N), 29.5, 29.4, 22.7 [(CH2)3], 26.9, 26.8, 26.3, 25.5
[2ϫC(CH3)2], 12.2 (CH3) ppm. C33H46N4O9 (642.74): calcd. C
(t, J = 6.9 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3): see 61.67, H 6.76, N 8.72; found C 61.81, H 6.92, N 8.89.
Table 3 and δ = 153.1 (C-1Ј), 150.2 (C-10Ј), 143.3 (C-7Ј), 129.1,
GAD 2-laA5-pr. Method A: The condensation of 6A-eth5 (1.59 g,
128.8, 125.1, 122.0, 111.1 (Ar-CH), 111.6, 108.7 [2 ϫC(CH3)2],
2.18 mmol) and 2 (0.70 g, 2.18 mmol), by the General Procedure,
71.2, 70.3, 68.2 (3ϫCH2O), 50.2 (CH3CH2N), 45.7 (CH2CH2N),
afforded 2-laA5-pr (1.12 g, 54% yield) as a red syrup after flash
29.3, 29.2, 22.6 [(CH2)3], 26.8, 26.7, 26.2, 25.3 [2ϫC(CH3)2], 12.2
chromatographic purification (hexane/EtOAc, 7:3). Rf = 0.27 (hex-
(CH3) ppm. C33H47N3O7 (597.76): calcd. C 66.31, H 7.93, N 7.03;
ane/EtOAc, 7:3). 1H NMR (200 MHz, CDCl3): δ = 8.32, 7.93
found C 66.28, H 7.90, N 7.00.
(AAЈXXЈ system, 4 H, 2Ј-H, 2Ј-H, 5Ј-H, 6Ј-H), 7.88, 6.76 (AAЈXXЈ
GAD 1-ga4-pr: Flash chromatography (hexane/EtOAc, 7:3) of the
crude product obtained by condensation of 5-eth4 (1.00 g,
2.53 mmol) and 1 (0.68 g, 2.53 mmol) afforded 1-ga4-pr (1.08 g,
73% yield) and 5-el4 (0.20 g, 25% yield).
system, 4 H, 8Ј-H, 9Ј-H, 11Ј-H, 12Ј-H), 4.59 (d, J1Ј,2Ј = 8.0 Hz, 1
H, 1Ј-H), 4.52 (dd, J1,2 = 6.4 Hz, J2,3 = 7.4 Hz, 1 H, 2-H), 4.37 (d,
1 H, 1-H), 4.26 (m, 1 H, 5-H), 4.18–3.98 (m, 6 H, 3-H, 4-H, 6a-H,
6b-H, 3Ј-H, 4Ј-H), 3.77–3.35 (m, 14 H, 5Ј-H, 6Јa-H, 6Јb-H, 2Ј-H,
3 ϫ CH2O, CH2CH2N, CH3CH2N), 3.42, 3.41(2 ϫ s, each 3 H,
2ϫ1-OCH3), 3.20 [s, 3 H, C(CH3)2OCH3], 1.60 [m, 6 H, (CH2)3],
1.50, 1.44, 1.39, 1.38, 1.33, 1.32 [6ϫs, each 3 H, 3ϫC(CH3)2], 1.31,
1.30 [2ϫs, each 3 H, C(CH3)2OCH3], 1.25 (t, J = 7.0 Hz, 3 H,
CH3) ppm. 13C NMR (50 MHz, CDCl3): see Table 5 and δ = 156.6
(C-1Ј), 152.3 (C-10Ј), 147.2 (C-4Ј), 143.5 (C-7Ј), 126.2, 124.6, 122.5,
111.3 (Ar-CH), 110.1, 109.4, 108.4 [3ϫC(CH3)2], 100.0 [C(CH3)2-
OCH3], 72.1 71.9, 68.2 [3ϫCH2O], 55.5, 53.1 (2ϫ1-OCH3), 48.5
[C(CH3)2OCH3], 50.4, 46.0 (2ϫCH2N), 29.8, 29.6, 22.6 [(CH2)3],
28.1, 27.5, 26.6, 26.5, 26.3, 25.7 [3ϫC(CH3)2], 24.4, 24.3 [C(CH3)2-
OCH3], 12.4 (CH3) ppm. C48H74N4O16 (963.12): calcd. C 59.86, H
7.74, N 5.82; found C 59.50, H 7.69, N 5.71.
Data for 1-ga4-pr: Syrup. Rf = 0.21 (hexane/EtOAc, 3:2). 1H NMR
(200 MHz, CDCl3): see Table 2 and δ = 7.85 (m, 4 H, 2Ј-H, 6Ј-H,
8Ј-H, 12Ј-H), 7.46 (m, 3 H, 3Ј-H, 4Ј-H, 5Ј-H), 6.74 (m, 2 H, 9Ј-H,
11Ј-H), 3.70–3.40 (m, 10 H, 2ϫCH2N, 3 ϫCH2O), 1.64 [m, 4 H,
(CH2)2], 1.53, 1.51, 1.44, 1.33 [4ϫs, each 3 H, 2ϫC(CH3)2], 1.21
(t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3): see
Table 3 and δ = 152.8 (C-1Ј), 149.9 (C-10Ј), 142.9 (C-7Ј), 128.8,
128.5, 124.9, 121.8, 110.7 (Ar-CH), 108.7, 108.0 [2 ϫC(CH3)2],
70.8, 70.7, 67.9 (3ϫCH2O), 49.9 (CH3CH2N), 45.3 (CH2CH2N),
26.0, 25.9 [(CH2)2], 25.7, 25.6, 24.6, 24.1 [2 ϫ C(CH3)2], 11.8
(CH3) ppm. C32H45N3O7 (583.73): calcd. C 65.84, H 7.77, N 7.20;
found C 65.78, H 7.74, N 7.18.
Method B: A mixture of 6A (1.00 g, 1.37 mmol), KOH (0.39 g,
6.85 mmol) and 18-crown-6 (0.01 equiv.) in THF/H2O (99.5:0.5,
10 mL) was stirred at room temperature for 1 h, 2-eth5 (0.64 g,
1.38 mmol) was then added, and the mixture was stirred under the
same conditions for several hours. TLC analysis (hexane/EtOAc,
5:1) revealed the complete disappearance of the starting material
(Rf = 0.79) and the formation of a minor faster-moving product
(Rf = 0.29). The mixture reaction was neutralised with saturated
aqueous NH4Cl (20 mL) and extracted with CH2Cl2 (3ϫ20 mL).
The organic phase was dried with Na2SO4, filtered and concen-
trated under diminished pressure, and the resulting residue was
purified by flash chromatography (hexane/EtOAc, 5:1) to yield 2-
laA5-pr (0.77 g, 57%), with NMR parameters identical to those of
the sample prepared above.
Data for 5-el4: Syrup. Rf = 0.52 (hexane/EtOAc, 3:2). [α]D = –60.3
(c = 1.0, CHCl3), ref.[13] [α]D = –61.0 (c = 1.13, CHCl3). NMR
spectroscopic data were in good agreement with the reported
ones.[13]
GAD 1-laB4-pr: The condensation of 6B-eth4 (1.18 g, 1.79 mmol)
and 1 (0.48 g, 1.79 mmol) afforded 1-laB4-pr (1.05 g, 69% yield) as
a yellow syrup after flash chromatographic purification (hexane/
EtOAc, 65:35). Rf = 0.45 (hexane/EtOAc, 2:3). 1H NMR
(250 MHz, CDCl3): δ = 7.84 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H, 12Ј-H),
7.42 (m, 3 H, 3Ј-H, 4Ј-H, 5Ј-H), 6.75 (m, 2 H, 9Ј-H, 11Ј-H), 4.60
(d, J1Ј,2Ј = 7.9 Hz, 1 H, 1Ј-H), 4.51 (dd, J1,2 = 6.3 Hz, J2,3 = 7.1 Hz,
1 H, 2-H), 4.35 (d, 1 H, 1-H), 4.25 (m, 1 H, 5-H), 4.16–3.95 (m, 7
H, 4Ј-H, 3Ј-H, 3-H, 4-H, 6a-H, 6b-H), 3.80 (m, 1 H, 5Ј-H), 3.70–
3.41 (m, 12 H, 6Јa-H, 6Јb-H, 2ϫCH2N, 3 ϫCH2O), 3.55 (s, 3 H,
2-OCH3), 3.42, 3.40 (2ϫs, each 3 H, 2ϫ1-OCH3), 3.09 (dd, J2Ј,3Ј
= 6.9 Hz, 2Ј-H), 1.64 [m, 4 H, (CH2)2], 1.51, 1.43, 1.40, 1.39, 1.35
1.32 [6 ϫ s, each 3 H, 3 ϫ C(CH3)2], 1.22 (t, J = 7.0 Hz, 3 H,
CH3) ppm. 13C NMR (62.9 MHz, CD3CN): see Table 5 and δ =
153.2 (C-1Ј), 150.2 (C-10Ј), 143.3 (C-7Ј), 129.2, 128.9, 125.1, 122.1,
111.1 (Ar-CH), 110.2, 109.6, 108.4 [3ϫC(CH3)2], 71.1, 69.3, 68.3
(3 ϫ CH2O), 60.2 (2-OCH3), 55.4, 53.2 (2 ϫ 1-OCH3), 50.2
(CH3CH2N), 45.8 (CH2CH2N), 28.0, 27.5, 26.5, 26.4, 26.2, 25.5
[3 ϫ C(CH3)2], 26.3 [(CH2)2], 12.2 (CH3) ppm. C44H67N3O13
(846.04): calcd. C 62.47, H 7.98, N 4.97; found C 62.44, H 7.79, N
4.94.
GAD 3-ga5-pr: The condensation of 5-eth5 (0.85 g, 2.08 mmol) and
3 (0.31 g, 2.08 mmol) afforded 3-ga5-pr (0.70 g, 56% yield) as a
red syrup after flash chromatographic purification (hexane/EtOAc,
1:1). Rf = 0.34 (hexane/EtOAc, 1:1). 1H NMR (200 MHz, CDCl3):
see Table 2 and δ = 7.90, 7.71 (AAЈXXЈ system, 4 H, 2Ј-H, 3Ј-H,
6Ј-H, 5Ј-H), 7.47 (d, J = 2.0 Hz, 1 H, 12Ј-H), 7.19 (dd, J = 8.6 Hz,
1 H, 10Ј-H), 6.97 (d, 1 H, 9Ј-H), 4.14 (t, J = 7.0 Hz, 2 H, CH2OPh),
3.50 (m, 2 H, CH2O), 2.32 (s, 3 H, CH3Ph), 2.03 (s, 3 H, CH3CO),
1.90 (m, 2 H, CH2); 1.70 (m, 4 H, CH2CH2), 1.51, 1.41, 1.32, 1.31
[4ϫs, each 3 H, 2ϫC(CH3)2] ppm. 13C NMR (50 MHz, CDCl3):
see Table 3 and δ = 168.9 (C=O), 154.6, 149.4, 142.3, 140.3 (C-1Ј,
C-4Ј, C-7Ј, C-8Ј), 130.5 (C-11Ј), 132.7, 123.9, 123.8, 119.6, 116.9,
115.0, (Ar-CH), 109.2, 108.6 [2ϫC(CH3)2], 71.5, 70.1 (2ϫCH2O),
29.3, 29.1, 22.7 [(CH2)3], 26.0, 25.9, 24.9, 24.4 [2ϫC(CH3)2], 24.6
(CH3Ph), 21.5 (CH3CO) ppm. C32H43N3O7 (597.71): calcd. C
64.30, H 7.25, N 7.03; found C 64.50, H 7.31, N 6.87.
GAD 2-gl5-pr: The condensation of 4-eth5 (0.87 g, 2.13 mmol) and
2 (0.67 g, 2.13 mmol) afforded 2-gl5-pr (1.16 g, 85% yield) as a red
syrup after flash chromatographic purification (hexane/EtOAc,
3:7). Rf = 0.29 (hexane/EtOAc, 3:7). 1H NMR (200 MHz, CDCl3):
see Table 2 and δ = 8.33, 7.93 (AAЈXXЈ system, 4 H, 2Ј-H, 3Ј-H,
5Ј-H, 6Ј-H), 7.91, 6.78 (AAЈXXЈ system, 4 H, 8Ј-H, 9Ј-H, 11Ј-H, GAD 3-laA5-pr: The condensation of 6A-eth5 (2.00 g, 2.74 mmol)
12Ј-H), 3.63–3.42 [m, 10 H, CH2CH2N, CH3CH2N, 3 ϫCH2O], and 3 (0.74 g, 2.74 mmol) afforded 3-laA5-pr (1.18 g, 47% yield) as
1.85 [m, 6 H, (CH2)3], 1.50, 1.43, 1.35, 1.32 [4 ϫ s, each 3 H,
a red syrup after flash chromatographic purification (hexane/
EtOAc, 1:2). Rf = 0.37 (hexane/EtOAc, 1:2). H NMR (200 MHz,
1
2 ϫ C(CH3)2], 1.26 (t, J = 7.4 Hz, 3 H, CH3) ppm. 13C NMR
(50 MHz, CDCl3): see Table 3 and δ = 157.6 (C-1Ј), 152.6 (C-10Ј), CDCl3): see Table 3 and δ = 7.91, 7.73 (AAЈXXЈ system, 4 H, 2Ј-
148.2 (C-4Ј), 144.2 (C-7Ј), 127.0, 125.7, 123.3, 122.5, 112.5 (Ar- H, 3Ј-H, 6Ј-H, 5Ј-H), 7.46 (d, J = 2.0 Hz, 1 H, 12Ј-H), 7.19 (dd, J
Eur. J. Org. Chem. 2008, 444–454
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