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(s, 1H), 7.50 (d, J = 8.7 Hz, 2H), 7.15 (s, 1H), 6.98 (d, J = 8.7 Hz, 2H),
6.23 (s, 2H), 5.00 (t, J = 6.1 Hz, 2H), 4.41 (t, J = 6.1 Hz, 2H), 4.15 (d,
J = 6.0 Hz, 2H), 4.11 (d, J = 6.1 Hz, 3H), 3.27 (s, 2H), 2.11–2.01 (m,
4H). LC/MS (ESI) m/z: [MÀBr]+ 548.1. Anal. Calcd for C29H27Br2NO5:
C, 55.35; H, 4.32; N, 2.23. Found: C, 55.33; H, 4.35; N, 2.24.
4.3.13. 9-O-[3-(Naphthalen-2-yloxy)propyl]-berberine bromide
(39b)
Berberrubine was treated with 19b according to general proce-
dure to give the desired product 39b as a yellow solid (55% yield).
Mp 201.0–212.3 °C; 1H NMR (400 MHz, DMSO-d6) d 9.80 (s, 1H),
8.92 (s, 1H), 8.15 (d, J = 9.1 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.85–
7.80 (m, 4H), 7.41 (t, J = 7.5 Hz, 1H), 7.35 (s, 1H), 7.30 (t,
J = 7.6 Hz, 1H), 7.13 (d, J = 9.0, Hz, 1H), 7.03 (s, 1H), 6.13 (s, 2H),
4.85 (t, J = 5.8 Hz, 2H), 4.48 (t, J = 6.2 Hz, 2H), 4.35 (t, J = 6.1 Hz,
2H), 4.00 (s, 3H), 3.11 (t, J = 6.2 Hz, 2H), 2.41–2.33 (m, 2H). LC/
MS (ESI) m/z: [MÀBr]+ 506.2. Anal. Calcd for C32H28BrNO5: C,
65.53; H, 4.81; N, 2.39. Found: C, 65.52; H, 4.83; N, 2.37.
4.3.8. 9-O-[3-(4-Nitro-phenoxyl)propyl]-berberine bromide
(35b)
Berberrubine was treated with 13b according to general proce-
dure to give the desired product 35b as a yellow solid (67% yield).
Mp 226.2–227.9 °C; 1H NMR (400 MHz, DMSO-d6) d 9.86 (s, 1H),
8.98 (s, 1H), 8.29 (d, J = 9.2 Hz, 2H), 8.24 (d, J = 9.2 Hz, 1H), 8.05
(d, J = 9.1 Hz, 1H), 7.85 (s, 1H), 7.26 (d, J = 9.3 Hz, 2H), 7.15 (s,
1H), 6.23 (s, 2H), 4.97 (t, J = 6.1 Hz, 2H), 4.54 (t, J = 6.2 Hz, 2H),
4.49 (t, J = 6.2 Hz, 2H), 4.05 (s, 3H), 3.31–3.21 (m, 2H), 2.44 (p,
J = 6.2 Hz, 2H). LC/MS (ESI) m/z: [MÀBr]+ 501.2. Anal. Calcd for
C28H25BrN2O7: C, 57.84; H, 4.33; N, 4.82. Found: C, 57.80; H,
4.31; N, 4.82.
4.3.14. 9-O-[3-(Naphthalen-2-yloxy)butyl]-berberine bromide
(39c)
Berberrubine was treated with 19c according to general proce-
dure to give the desired product 39c as a yellow solid (47% yield).
Mp 182.5–183.9 °C; 1H NMR (400 MHz, DMSO-d6) d 9.77 (s, 1H),
8.90 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.98 (d, J = 9.0 Hz, 1H), 7.81–
7.77 (m, 4H), 7.43 (t, J = 7.6 Hz, 1H), 7.41–7.32 (m, 2H), 7.14 (d,
J = 9.0, Hz, 1H), 7.01 (s, 1H), 6.16 (s, 2H), 4.92 (t, J = 6.0 Hz, 2H),
4.39 (t, J = 6.1 Hz, 2H), 4.21 (t, J = 6.1 Hz, 2H), 4.01 (s, 3H), 3.18 (t,
J = 6.1 Hz, 2H), 2.06–1.97 (m, 2H). LC/MS (ESI) m/z: [MÀBr]+
520.2. Anal. Calcd for C33H30BrNO5: C, 66.00; H, 5.04; N, 2.33.
Found: C, 65.97; H, 5.07; N, 2.34.
4.3.9. 9-O-[3-(4-Nitro-phenoxyl)butyl]-berberine bromide (35c)
Berberrubine was treated with 13c according to general proce-
dure to give the desired product 35c as a yellow solid (70% yield).
Mp 215.5–217.8 °C; 1H NMR (400 MHz, DMSO-d6) d 9.77 (s, 1H),
8.93 (s, 1H), 8.20 (dd, J = 9.3, 3.0 Hz, 3H), 8.00 (d, J = 9.1 Hz, 1H),
7.79 (s, 1H), 7.16 (d, J = 9.2 Hz, 2H), 7.09 (s, 1H), 6.18 (s, 2H), 4.94
(t, J = 5.9 Hz, 2H), 4.37 (t, J = 5.7 Hz, 2H), 4.26 (t, J = 5.5 Hz, 2H),
4.05 (s, 3H), 3.21 (t, J = 6.0 Hz, 2H), 2.04 (m, 4H). LC/MS (ESI) m/z:
[MÀBr]+ 515.2. Anal. Calcd for C29H27BrN2O7: C, 58.50; H, 4.57;
N, 4.70. Found: C, 58.51; H, 4.58; N, 4.67.
4.3.15. 9-O-[3-(Naphthalene-2-ylthio)propyl]-berberine
bromide (40b)
Berberrubine was treated with 20b according to general proce-
dure to give the desired product 40b as a yellow solid (27% yield).
Mp 193.7–195.9 °C; 1H NMR (400 MHz, DMSO-d6) d 9.81 (s, 1H),
8.93 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 8.00 (d, J = 9.0 Hz, 1H), 7.88–
7.85 (m, 4H), 7.79 (s, 1H), 7.50–7.48 (m, 3H), 7.09 (s, 1H), 6.18 (s,
2H), 4.92 (t, J = 6.0 Hz, 2H), 4.46 (t, J = 6.1 Hz, 2H), 4.03 (s, 3H),
3.19 (m, 4H), 2.26–2.23 (m, 2H). LC/MS (ESI) m/z: [MÀBr]+ 522.2.
Anal. Calcd for C32H28BrNO4S: C, 63.79; H, 4.68; N, 2.32. Found:
C, 63.55; H, 4.60; N, 2.23.
4.3.10. 9-O-[3-(2-Pyridinoxyl)butyl]-berberine bromide (36c)
Berberrubine was treated with 14c according to general proce-
dure to give the desired product 36c as a yellow solid (40% yield).
Mp 197.7–199.5 °C; 1H NMR (400 MHz, DMSO-d6) d 8.86 (s, 1H),
8.12 (d, J = 9.1 Hz, 1H), 7.93 (d, J = 9.1 Hz, 1H), 7.72 (s, 1H), 7.68
(d, J = 5.9 Hz, 1H), 7.39–7.34 (m, 1H), 7.03 (s, 1H), 6.33 (d,
J = 9.1 Hz, 1H), 6.19 (t, J = 6.6 Hz, 1H), 6.12 (s, 2H), 4.93 (t,
J = 5.7 Hz, 2H), 4.27 (t, J = 5.2 Hz, 2H), 3.99 (s, 3H), 3.94 (t,
J = 6.2 Hz, 2H), 3.20–3.14 (m, 2H), 1.83 (m, 5H). LC/MS (ESI) m/z:
[MÀBr]+ 471.2. Anal. Calcd for C28H27BrN2O5: C, 60.99; H, 4.94;
N, 5.08. Found: C, 61.09; H, 5.10; N, 5.20.
4.3.16. 9-O-[3-(Naphthalene-2-ylthio)butyl]-berberine bromide
(40c)
Berberrubine was treated with 20c according to general proce-
dure to give the desired product 40c as a yellow solid (32% yield).
Mp 173.1–175.8 °C; 1H NMR (400 MHz, DMSO-d6) d 9.73 (s, 1H),
8.90 (s, 1H), 8.18 (d, J = 9.2 Hz, 1H), 7.98 (d, J = 9.1 Hz, 1H), 7.84–
7.81 (m, 4H), 7.78 (s, 1H), 7.52–7.41 (m, 3H), 7.08 (s, 1H), 6.18 (s,
2H), 4.89 (t, J = 6.2 Hz, 2H), 4.34 (t, J = 6.4 Hz, 2H), 4.03 (s, 3H),
3.22 (t, J = 7.2 Hz, 2H), 3.19–3.15 (m, 2H), 2.08–2.03 (m, 2H),
1.94–1.86 (m, 2H). LC/MS (ESI) m/z: [MÀBr]+ 536.2. Anal. Calcd
for C33H30BrNO4S: C, 64.28; H, 4.90; N, 2.27. Found: C, 64.20; H,
4.71; N, 2.20.
4.3.11. 9-O-[3-(Phenylamino)propyl]-berberine bromide (37b)
Berberrubine was treated with 15b according to general proce-
dure to give the desired product 37b as a yellow solid (38% yield).
Mp 193.5–196.0 °C; 1H NMR (400 MHz, DMSO-d6) d 9.73 (s, 1H),
8.92 (s, 1H), 8.19 (d, J = 9.2 Hz, 1H), 8.00 (d, J = 9.1 Hz, 1H), 7.79
(s, 1H), 7.09 (t, J = 7.9 Hz, 3H), 6.61 (d, J = 7.8 Hz, 2H), 6.54 (t,
J = 7.3 Hz, 1H), 6.17 (s, 2H), 4.85 (t, J = 6.2 Hz, 2H), 4.42 (t,
J = 6.3 Hz, 2H), 4.04 (s, 3H), 3.29 (t, J = 6.7 Hz, 2H), 3.18 (t,
J = 6.4 Hz, 2H), 2.20–2.10 (m, 2H). LC/MS (ESI) m/z: [MÀBr]+
455.2. Anal. Calcd for C28H27BrN2O4: C, 62.81; H, 5.08; N, 5.23.
Found: C, 62.51; H, 4.98; N, 5.29.
4.4. General procedures for the preparation of 26–30
To the substituted anilines (21–25) (10 mmol) solution in chlo-
roform (re-distilled, 50 ml), b-bromopropionyl chloride (11 mmol)
was slowly added at 0 °C, and then pyridine (11 mmol). After stir-
red for 1 h at room temperature, the reaction mixture was washed
with NaHCO3 solution (2 Â 50 ml), water (2 Â 50 ml), brine
(1 Â 50 ml), and then dried with anhydrous Na2SO4, concentrated
in vacuo to afford the resulting compound (26–30) which was used
for the next step without purification.
4.3.12. 9-O-[3-(N-Methyl-phenylamino)propyl]-berberine
bromide (38b)
Berberrubine was treated with 16b according to general proce-
dure to give the desired product 38b as a yellow solid (43% yield).
Mp 207.3–210.0 °C; 1H NMR (400 MHz, DMSO-d6) d 9.71 (s, 1H),
8.89 (s, 1H), 8.15 (d, J = 9.2 Hz, 1H), 7.96 (d, J = 9.1 Hz, 1H), 7.75
(s, 1H), 7.13 (t, J = 7.9 Hz, 2H), 7.04 (s, 1H), 6.71 (d, J = 8.1 Hz,
2H), 6.57 (t, J = 7.1 Hz, 1H), 6.13 (s, 2H), 4.87 (t, J = 6.4 Hz, 2H),
4.33 (t, J = 6.2 Hz, 2H), 3.99 (s, 3H), 3.57 (t, J = 6.3 Hz, 2H), 3.17 (t,
J = 6.0 Hz, 2H), 2.89 (s, 3H), 2.14–2.03 (m, 2H). LC/MS (ESI) m/z:
[MÀBr]+ 469.2. Anal. Calcd for C29H29BrN2O4: C, 63.39; H, 5.32;
N, 5.10. Found: C, 63.46; H, 5.50; N, 5.00.
4.5. General procedures for the preparation of 41–45
Compounds 26–30 (2.4 mmol) was added to a magnetically
stirred suspension of berberrubine (2 mmol) in CH3CN (15 mL)