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4.3.3. 4-N-(2-Aminopyridine)-4-deoxidation-40-
podophyllotoxin (2g)
C26H23ClN2O7: C, 61.12; H, 4.54; N, 5.48. Found: C, 61.27; H,
4.66; N, 5.26.
The yield 28%; white powder, 1H NMR (300 MHz, CD3OD, 25 °C,
TMS): d = 3.04 (s, 1H; H-3), 3.05 (s, 1H; H-2), 3.71 (s, 3H; OCH3),
3.73 (s, 6H; OCH3), 4.62 (s, 2H; H-11), 4.63 (s, 1H; H-1), 5.08 (s,
1H; H-4), 5.98 (s, 2H; H-13), 6.28 (s, 2H; Ar-H), 6.52 (s, 1H; Ar-H),
6.81 (t, J = 6 Hz, 1H; Ar-H), 7.00 (d, J = 12 Hz, 2H; Ar-H), 7.80 ppm
(d, J = 6 Hz, 2H; Ar-H); 13C NMR (75 MHz, CD3OD, 25 °C, TMS):
d = 38.30 (C-3), 42.16 (C-2), 51.71 (C-1), 52.84 (C-4), 55.37 (OCH3),
59.87 (OCH3), 69.13 (C-11), 101.85 (C-13), 107.02 (Ar-C), 108.27
(Ar-C), 109.58 (Ar-C), 113.09 (Ar-C), 114.59 (Ar-C), 125.62 (Ar-C),
131.29 (Ar-C), 137.03 (Ar-C), 138.81 (Ar-C), 141.95 (Ar-C), 147.72
(Ar-C), 149.08 (Ar-C), 151.12 (Ar-C), 153.06 (Ar-C), 172.49 ppm (C-
12). MS (ESI): m/z: 490.17 [M+H]+; Anal. Calcd for C27H26N2O7: C,
66.11; H, 5.34; N, 5.71. Found: C, 65.95; H, 5.27; N, 5.53.
4.3.7. 4-N-(2-Amino-4-chloropyridine)-4-deoxidation-40-
podophyllotoxin (4g)
The yield 51%; white powder, 1H NMR (400 MHz, CDCL3, 25 °C,
TMS): d = 2.95 (s, 1H; H-3), 2.96 (s, 1H; H-2), 3.68 (s, 6H; OCH3),
3.69 (s, 3H; OCH3), 3.73 (d, J = 8 Hz, 1H; H-11), 4.31 (d, J = 8 Hz,
1H; H-11), 4.46 (d, J = 4 Hz, 1H; H-1), 5.19 (d, J = 8 Hz, 1H; H-4),
5.32 (s, 1H; exchangeable NH), 5.81 (s, 1H; H-13), 5.87 (s, 1H; H-
13), 6.25 (s, 2H; Ar-H), 6.42 (s, 2H; Ar-H), 6.56 (d, J = 8 Hz, 1H;
Ar-H), 6.75 (s, 1H; Ar-H), 7.90 ppm (d, J = 4 Hz, 1H; Ar-H); 13C
NMR (100 MHz, CDCL3, 25 °C, TMS): d = 38.08 (C-3), 41.74 (C-2),
43.69 (C-1), 49.61 (C-4), 56.07 (OCH3), 60.61 (OCH3), 69.67 (C-
11), 101.44 (C-13), 108.03 (Ar-C), 108.23 (Ar-C), 109.36 (Ar-C),
114.19 (Ar-C), 130.27 (Ar-C), 132.06 (Ar-C), 135.26 (Ar-C), 136.80
(Ar-C), 144.46 (Ar-C), 147.38 (Ar-C), 147.95 (Ar-C), 148.60 (Ar-C),
152.44 (Ar-C), 158.39 (Ar-C), 175.08 ppm (C-12). MS (ESI): m/z:
524.14 [M+H]+; Anal. Calcd for C27H25ClN2O7: C, 61.78; H, 4.80;
N, 5.34. Found: C, 61.66; H, 4.79; N, 5.25.
4.3.4. 4-N-(2-Aminopyridine)-4-deoxidation-40-
demethylepipodophyllotoxin (2h)
The yield 30%; white powder, 1H NMR (300 MHz, CD3OD, 25 °C,
TMS): d = 3.03 (s, 1H; H-3), 3.04 (s, 1H; H-2), 3.71 (d, J = 9 Hz, 6H;
OCH3), 3.78 (s, 1 H; H-11), 4.59 (s, 1H; H-11), 4.63 (s, 1H; H-1),
5.05 (s, 1H; H-4), 5.98 (s, 2H; H-13), 6.25 (s, 2H; Ar-H), 6.52 (s,
1H; Ar-H), 6.83 (d, J = 6 Hz, 1H; Ar-H), 6.98 (d, J = 15 Hz, 2H; Ar-
H), 7.79 ppm (d, J = 6 Hz, 2H; Ar-H); 13C NMR (75 MHz, CD3OD,
25 °C, TMS): d = 40.71 (C-3), 41.83 (C-2), 50.22 (C-1), 51.32 (C-4),
53.97 (OCH3), 59.11 (C-11), 100.24 (C-13), 105.36 (Ar-C), 106.59
(Ar-C), 108.07 (Ar-C), 111.50 (Ar-C), 113.00 (Ar-C), 123.97 (Ar-C),
128.13 (Ar-C), 130.15 (Ar-C), 133.30 (Ar-C), 137.26 (Ar-C), 140.36
(Ar-C), 146.24 (Ar-C), 147.46 (Ar-C), 149.57 (Ar-C), 171.74 ppm
(C-12). MS (ESI): m/z: 476.16 [M+H]+; Anal. Calcd for C26H24N2O7:
C, 65.54; H, 5.08; N, 5.88. Found: C, 65.29; H, 5.00; N, 5.71.
4.3.8. 4-N-(2-Amino-4-chloropyridine)-4-deoxidation-40-
demethylepipodophyllotoxin (4h)
The yield 48%; white powder, 1H NMR (400 MHz, CD3OD and
CDCL3, 25 °C, TMS): d = 3.18 (s, 1H; H-3), 3.19 (s, 1H; H-2), 3.78
(s, 6H; OCH3), 3.85 (d, J = 8 Hz, 1H; H-11), 4.40 (t, J = 8 Hz, 1H; H-
11), 4.61 (d, J = 4 Hz, 1H; H-1), 4.87 (d, J = 4 Hz, 1H; H-4), 5.97 (d,
J = 4 Hz, 2H; H-13), 6.34 (s, 2H; Ar-H), 6.54 (d, J = 8 Hz, 2H; Ar-H),
6.64 (s, 1H; Ar-H), 6.76 (s, 1H; Ar-H), 7.53 ppm (s, 1H; Ar-H); 13C
NMR (100 MHz, CD3OD and CDCL3, 25 °C, TMS): d = 42.12 (C-3),
45.57 (C-2), 47.31 (C-1), 54.67 (C-4), 59.99 (OCH3), 72.41 (C-11),
105.47 (C-13), 111.93 (Ar-C), 112.96 (Ar-C), 113.66 (Ar-C), 130.47
(Ar-C), 132.80 (Ar-C), 133.56 (Ar-C), 134.04 (Ar-C), 135.99 (Ar-C),
138.35 (Ar-C), 147.50 (Ar-C), 150.97 (Ar-C), 151.46 (Ar-C), 152.32
(Ar-C), 159.79 (Ar-C), 179.36 ppm (C-12). MS (ESI): m/z: 510.12
[M+H]+; Anal. Calcd for C26H23ClN2O7: C, 61.12; H, 4.54; N, 5.48.
Found: C, 61.18; H, 4.50; N, 5.28.
4.3.5. 4-N-(2-Amino-3-chloropyridine)-4-deoxidation-40-
podophyllotoxin (3g)
The yield 46%; white powder, 1H NMR (400 MHz, CDCL3, 25 °C,
TMS): d = 3.04 (s, 1H; H-3), 3.05 (s, 1H; H-2), 3.71 (s, 6H; OCH3),
3.73 (d, J = 4 Hz, 1 H; H-11), 3.76 (s, 3H; OCH3), 4.33 (t, J = 8 Hz, 1
H; H-11), 4.57 (d, J = 4 Hz, 1H; H-1), 5.08 (d, J = 8 Hz, 1H; H-4),
5.38 (d, J = 4 Hz, 1H; exchangeable NH), 5.90 (d, J = 4 Hz, 2H; H-
13), 6.30 (s, 2H; Ar-H), 6.47 (s, 1H; Ar-H), 6.58–6.61 (m, 1H; Ar-
H), 6.75 (s, 1H; Ar-H), 7.45 (d, J = 4 Hz, 1H; Ar-H), 7.97 ppm (d,
J = 4 Hz, 1H; Ar-H); 13C NMR (100 MHz, CDCL3, 25 °C, TMS):
d = 38.14 (C-3), 41.89 (C-2), 43.76 (C-1), 50.00 (C-4), 56.14
(OCH3), 60.69 (OCH3), 69.74 (C-11), 101.52 (C-13), 108.16 (Ar-C),
109.20 (Ar-C), 109.89 (Ar-C), 114.32 (Ar-C), 115.17 (Ar-C), 130.08
(Ar-C), 132.34 (Ar-C), 135.14 (Ar-C), 136.51 (Ar-C), 145.77 (Ar-C),
147.60 (Ar-C), 148.26 (Ar-C), 152.51 (Ar-C), 153.15 (Ar-C),
174.82 ppm (C-12). MS (ESI): m/z: 524.14 [M+H]+; Anal. Calcd for
4.3.9. 4-N-(2-Amino-5-chloropyridine)-4-deoxidation-40-
podophyllotoxin (5g)
The yield 39%; white powder, 1H NMR (400 MHz, CDCL3, 25 °C,
TMS): d = 2.97 (s, 1H; H-3), 2.98 (s, 1H; H-2), 3.69 (s, 6H; OCH3),
3.72 (s, 3H; OCH3), 3.74 (d, J = 8 Hz, 1H; H-11), 4.33 (s, 1H; H-
11), 4.48 (d, J = 4 Hz, 1H; H-1), 4.98 (d, J = 4 Hz, 1H; H-4), 5.28 (s,
1H; exchangeable NH), 5.85 (s, 1H; H-13), 5.89 (s, 1H; H-13),
6.26 (s, 2H; Ar-H), 6.35 (d, J = 8 Hz, 1H; Ar-H), 6.44 (s, 1H; Ar-H),
6.75 (s, 1H; Ar-H), 7.29 (d, J = 4 Hz, 1H; Ar-H), 7.97 ppm (d,
J = 4 Hz, 1H; Ar-H); 13C NMR (100 MHz, CDCL3, 25 °C, TMS):
d = 38.16 (C-3), 41.80 (C-2), 43.69 (C-1), 49.86 (C-4), 56.10
(OCH3), 60.66 (OCH3), 69.73 (C-11), 101.47 (C-13), 108.09 (Ar-C),
109.32 (Ar-C), 109.56 (Ar-C), 109.77 (Ar-C), 120.63 (Ar-C), 130.33
(Ar-C), 132.07 (Ar-C), 135.21 (Ar-C), 137.24 (Ar-C), 145.89 (Ar-C),
147.43 (Ar-C), 148.01 (Ar-C), 152.46 (Ar-C), 155.87 (Ar-C),
175.08 ppm (C-12). MS (ESI): m/z: 524.14 [M+H]+; Anal. Calcd for
C27H25ClN2O7: C, 61.78; H, 4.80; N, 5.34. Found: C, 61.79; H,
4.75; N, 5.27.
4.3.6. 4-N-(2-Amino-3-chloropyridine)-4-deoxidation-40-
demethylepipodophyllotoxin (3h)
The yield 42%; white powder, 1H NMR (400 MHz, CDCL3, 25 °C,
TMS): d = 3.04 (s, 1H; H-3), 3.06 (s, 1H; H-2), 3.73 (d, J = 12 Hz, H;
H-11), 3.79 (s, 6H; OCH3), 4.38 (d, J = 8 Hz, 1H; H-11), 4.60 (d,
J = 4 Hz, 1H; H-1), 5.09 (d, J = 4 Hz, 1H; H-4), 5.41 (s, 1H; exchange-
able NH), 5.95 (d, J = 4 Hz, 2H; H-13), 6.33 (s, 2H; Ar-H), 6.53 (s, 1H;
Ar-H), 6.62–6.65 (m, 1H; Ar-H), 6.78 (s, 1H; Ar-H), 7.49 (d, J = 8 Hz,
1H; Ar-H), 8.00 ppm (t, J = 4 Hz, 1H; Ar-H); 13C NMR (100 MHz,
CDCL3, 25 °C, TMS): d = 38.07 (C-3), 42.05 (C-2), 43.62 (C-1),
50.02 (C-4), 56.40 (OCH3), 69.76 (C-11), 101.52 (C-13), 107.89
(Ar-C), 109.17 (Ar-C), 109.96 (Ar-C), 114.32 (Ar-C), 115.22 (Ar-C),
130.08 (Ar-C), 130.57 (Ar-C), 132.56 (Ar-C), 136.53 (Ar-C), 145.79
(Ar-C), 146.43 (Ar-C), 147.58 (Ar-C), 148.26 (Ar-C), 153.18 (Ar-C),
174.93 ppm (C-12). MS (ESI): m/z: 510.12 [M+H]+; Anal. Calcd for
C27H25ClN2O7: C, 61.78; H, 4.80; N, 5.34. Found: C, 61.61; H,
4.91; N, 5.08.
4.3.10. 4-N-(2-Amino-5-chloropyridine)-4-deoxidation-40-
demethylepipodophyllotoxin (5h)
The yield 37%; white powder, 1H NMR (400 MHz, CDCL3, 25 °C,
TMS): d = 2.97 (s, 1H; H-3), 2.98 (s, 1H; H-2), 3.73 (s, 6H; OCH3),
3.75 (d, J = 12 Hz, 1H; H-11), 4.34 (s, 1H; H-11), 4.50 (s, 1H; H-1),
4.88 (d, J = 8 Hz, 1H; H-4), 5.27 (d, J = 8 Hz, 1H; exchangeable
NH), 5.88 (s, 1H; H-13), 5.92 (s, 1H; H-13), 6.28 (s, 2H; Ar-H),
6.37 (d, J = 8 Hz, 1H; Ar-H), 6.47 (s, 1H; Ar-H), 6.76 (s, 1H; Ar-H),
7.32 (d, J = 12 Hz, 1H; Ar-H), 8.00 ppm (d, J = 4 Hz, 1H; Ar-H); 13C