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3H); 13C NMR (CDCl3, 100 MHz) d 158.87, 156.78, 148.19, 146.37,
137.25 (2C), 136.13, 129.53, 128.49 (2C), 127.78, 127.44 (2C),
115.78, 111.91, 111.74, 103.84, 95.93, 71.52, 58.89, 55.91, 55.29,
53.29, 51.38, 37.12, 29.02; ESI-MS m/z 432 [M+H]+.
6.31 (s, 1H), 5.04 (dd, J = 28.4, 10.8 Hz, 2H), 4.11–4.07 (m, 1H),
3.97–3.93 (m, 1H), 3.91 (s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.80 (s,
3H), 3.77–3.73 (m, 1H), 3.48 (dd, J = 16.4, 3.6 Hz, 1H), 3.16–3.00
(m, 2H), 2.86–2.67 (m, 3H); 13C NMR (CDCl3, 100 MHz) d 158.73,
156.99, 152.05, 151.18, 139.01, 137.69, 137.05, 130.82, 128.18
(2C), 128.15 (2C), 127.74, 124.23, 115.47, 107.37, 103.84, 95.86,
75.03, 60.79, 55.77, 55.21, 55.15, 55.10, 52.63, 48.13, 33.76,
30.24; ESI-MS m/z 462 [M+H]+.
6.7.2. (S)-2-(Benzyloxy)-3,11-dimethoxytetrahydroprotoberber-
ine (18a)
Yield 86%; mp 107–110 °C; 1H NMR (CDCl3, 400 MHz) d 7.46 (d,
J = 7.2 Hz, 2H), 7.40–7.30 (m, 3H), 6.99 (d, J = 8.4 Hz, 1H), 6.76 (s,
1H), 6.72 (dd, J = 8.4, 2.8 Hz, 1H), 6.66 (d, J = 2.4 Hz, 1H), 6.64 (s,
1H), 5.15 (s, 2H), 3.99–3.94 (m, 1H), 3.88 (s, 3H), 3.79 (s, 3H),
3.64 (d, J = 14.4 Hz, 1H), 3.55–3.51 (m, 1H), 3.16–3.11 (m, 3H),
2.78 (dd, J = 16.4, 11.2 Hz, 1H), 2.69–2.58 (m, 2H); ESI-MS m/z
402 [M+H]+.
6.7.10. (S)-1,3,9,11-Tetramethoxytetrahydroprotoberberine
(18j)
Yield 84%; mp 90–92 °C; 1H NMR (CDCl3, 300 MHz) d 6.32 (d,
J = 2.4 Hz, 1H), 6.29 (dd, J = 4.2, 2.1 Hz, 2H), 6.24 (d, J = 2.7 Hz,
1H), 4.15–4.01 (m, 2H), 3.90–3.82 (m, 1H), 3.79 (s, 9H), 3.78 (s,
3H), 3.48 (dd, J = 16.8, 3.3 Hz, 1H), 3.20–3.03 (m, 2H), 2.94–2.89
(m, 1H), 2.81–2.67 (m, 2H); 13C NMR (CDCl3, 100 MHz) d 158.99
(2C), 157.48, 157.12, 136.57, 136.34, 118.84, 114.45, 104.27,
103.87, 96.59, 96.01, 55.29, 55.24 (2C), 55.16, 54.69, 52.42, 47.81,
33.08, 30.05; ESI-MS m/z 356 [M+H]+.
6.7.3. (S)-2,3-Methylenedioxy-9,11-dimethoxy-12-hydroxyme-
thyltetrahydroprotoberberine (18b)
Yield 79%; mp 134 °C; 1H NMR (CDCl3, 300 MHz) d 6.79 (s, 1H),
6.59 (s, 1H), 6.36 (s, 1H), 5.92 (s, 2H), 4.77–4.61 (m, 2H), 4.12 (d,
J = 15.3 Hz, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.54 (d, J = 11.4 Hz, 1H),
3.49–3.36 (m, 2H), 3.18–3.07 (m, 2H), 2.84–2.75 (m, 1H), 2.68–
2.59 (m, 2H), 1.83 (br, 1H); NOE 6.36 (1H) connected with 3.87
(3H) and 3.85 (3H); ESI-MS m/z 370 [M+H]+.
6.7.11. (S)-1,2,3,9,11-pentamethoxytetrahydroprotoberberine
(18k)
Yield 74%; mp 171–174 °C; 1H NMR (CDCl3, 300 MHz) d 6.46 (s,
1H), 6.33 (d, J = 1.8 Hz, 1H), 6.28 (s, 1H), 4.22–4.14 (m, 2H), 4.05–
3.96 (m, 1H), 3.92 (s, 3H), 3.87 (s, 3H), 3.86 (s, 3H), 3.81 (s, 3H),
3.79 (s, 3H), 3.46 (dd, J = 17.1, 4.2 Hz, 1H), 3.26–3.19 (m, 1H),
3.09–3.05 (m, 2H), 2.96–2.79 (m, 2H); ESI-MS m/z 386 [M+H]+.
6.7.4. (S)-2,3,11-Trimethoxytetrahydroprotoberberine (18d)
Yield 87%; 1H NMR (CDCl3, 300 MHz) d 7.00 (d, J = 8.4 Hz, 1H),
6.74 (s, 2H), 6.71 (s, 1H), 6.62 (s, 1H), 3.96–3.94 (m, 1H), 3.90 (s,
3H), 3.87 (s, 3H), 3.79 (s, 3H), 3.69–3.58 (m, 2H), 3.30 (dd,
J = 16.5, 3.6 Hz, 1H), 3.19–3.12 (m, 2H), 2.94–2.79 (m, 1H), 2.69–
2.63 (m, 2H); ESI-MS m/z 326 [M+H]+.
6.7.12. (S)-1,2,3,9,11-Pentamethoxy-12-hydromethyltetrahy-
droprotoberberine (18l)
Yield 77%; mp 91–93 °C; chiral HPLC: hexane/i-PrOH = 70/30,
flow rate = 0.6 ml/mim, k = 214 nm, 99% ee; 1H NMR (CDCl3,
300 MHz) d 6.45 (s, 1H), 6.40 (s, 1H), 4.65 (s, 2H), 4.30–4.25 (m,
2H), 4.18–4.10 (m, 1H), 3.94 (d, J = 0.9 Hz, 3H), 3.88 (s, 3H), 3.86
(s, 6H), 3.84 (s, 3H), 3.68 (dd, J = 17.7, 4.2 Hz, 1H), 3.27–3.22 (m,
2H), 3.06–2.94 (m, 2H), 2.88–2.78 (m, 1H); 13C NMR (CDCl3,
6.7.5. (S)-2,3-Methylenedioxy-11-methoxytetrahydroprotober-
berine (18e)
Yield 82%; mp 114–116 °C; 1H NMR (CDCl3, 300 MHz) d 7.00 (d,
J = 8.4 Hz, 1H), 6.74–6.69 (m, 3H), 6.59 (s, 1H), 5.92 (s, 2H), 3.96 (d,
J = 14.4 Hz, 1H), 3.78 (s, 3H), 3.68–3.55 (m, 2H), 3.29–3.22 (m, 1H),
3.16–3.06 (m, 2H), 2.87 (dd, J = 15.9, 11.4 Hz, 1H), 2.67–2.55 (m,
2H); ESI-MS m/z 310 [M+H]+.
100 MHz)
d 157.39, 156.72, 152.10, 150.74, 140.13, 135.52,
129.98, 123.88, 118.60, 114.66, 107.23, 92.42, 60.74, 60.65, 56.11,
55.84, 55.70, 55.31, 54.49, 52.36, 47.37, 30.15, 29.66; ESI-MS m/z
416 [M+H]+.
6.7.6. (S)-2,3,9,11-Tetramethoxytetrahydroprotoberberine (18f)
Yield 85%; mp 153–156 °C; 1H NMR (CDCl3, 300 MHz) d 6.73 (s,
1H), 6.61 (s, 1H), 6.30 (s, 2H), 4.10 (d, J = 15.3 Hz, 1H), 3.88 (s, 3H),
3.86 (s, 3H), 3.79 (s, 3H), 3.78 (s, 3H), 3.70–3.55 (m, 2H), 3.28–3.08
(m, 3H), 2.94–2.83 (m, 1H), 2.67–2.60 (m, 2H); ESI-MS m/z 356
[M+H]+.
6.7.13. (S)-1,2,3-Trimethoxy-10,11-methylenedioxytetrahydro-
protoberberine (18m)
Yield 86%; mp 89–91 °C; 1H NMR (CDCl3, 300 MHz) d 6.58 (s,
1H), 6.55 (s, 1H), 6.45 (s, 1H), 5.29 (s, 2H), 4.12 (d, J = 14.7 Hz,
1H), 4.07–4.01 (m, 1H), 3.95–3.91 (m, 4H), 3.87 (s, 3H), 3.84 (s,
3H), 3.36 (dd, J = 16.8, 4.2 Hz, 1H), 3.15–3.08 (m, 1H), 3.02–2.88
(m, 2H), 2.77–2.66 (m, 2H); 13C NMR (CDCl3, 100 MHz) d 152.06,
150.53, 146.12, 145.80, 140.21, 129.63, 127.35, 125.86, 123.53,
108.46, 107.21, 106.07, 100.54, 60.80, 60.60, 57.31, 55.75, 54.81,
47.17, 32.74, 29.52; ESI-MS m/z 370 [M+H]+.
6.7.7. (S)-2,3,9,11-Tetramethoxy-12-hydroxymethyltetrahydro-
protoberberine (18g)
Yield 76%; mp 132–133 °C; 1H NMR (CDCl3, 300 MHz) d 6.77 (s,
1H), 6.61 (s, 1H), 6.36 (s, 1H), 4.77–4.61 (m, 2H), 4.11 (d,
J = 15.3 Hz, 1H), 3.89 (s, 3H), 3.86 (s, 6H), 3.85 (s, 3H), 3.55–3.36
(m, 3H), 3.18–3.07 (m, 2H), 2.82–2.74 (m, 1H), 2.68–2.56 (m,
2H), 2.04 (br, 1H); ESI-MS m/z 386 [M+H]+.
6.7.14. (S)-1,3-Dimethoxy-4-hydromethyl-10,11-methylenedi-
oxytetrahydroprotoberberine (18n)
6.7.8. (S)-2,3-Methylenedioxy-9,11-dimethoxytetrahydroproto-
berberine (18h)
Yield 73%; mp 164–165 °C; 1H NMR (CDCl3, 300 MHz) d 6.54 (s,
2H), 6.38 (s, 1H), 5.88 (s, 2H), 4.67 (s, 2H), 4.06–3.97 (m, 2H), 3.87
(s, 3H), 3.84 (s, 3H), 3.81–3.75 (m, 1H), 3.32 (dd, J = 16.5, 3.9 Hz,
1H), 3.13–3.00 (m, 3H), 2.68–2.56 (m, 2H), 2.18 (br, 1H); ESI-MS
m/z 370 [M+H]+.
Yield 83%; mp 155–157 °C; 1H NMR (CDCl3, 300 MHz) d 6.73 (s,
1H), 6.59 (s, 1H), 6.30 (s, 2H), 5.92 (s, 2H), 4.10 (d, J = 15.3 Hz, 1H),
3.80 (s, 3H), 3.79 (s, 3H), 3.54 (d, J = 10.5 Hz, 1H), 3.38 (d,
J = 15.3 Hz, 1H), 3.24–3.08 (m, 3H), 2.90–2.81 (m, 1H), 2.66–2.57
(m, 2H); ESI-MS m/z 340 [M+H]+.
6.7.15. (S)-1,3,11-Trimethoxy-4-hydromethyltetrahydroproto-
berberine (18o)
6.7.9. (S)-2-(Benzyloxy)-1,3,9,11-tetramethoxytetrahydroproto-
Yield 76%; mp 121–122 °C; 1H NMR (CDCl3, 300 MHz) d 7.00 (d,
J = 8.4 Hz, 1H), 6.74 (dd, J = 8.4, 2.7 Hz, 1H), 6.62 (d, J = 2.4 Hz, 1H),
6.38 (s, 1H), 4.66 (s, 2H), 4.25–4.18 (m, 2H), 3.98 (d, J = 15.6 Hz,
1H), 3.86 (s, 3H), 3.85 (s, 3H), 3.77 (s, 3H), 3.48–3.41 (m, 1H),
berberine (18i)
Yield 85%; mp 124–125 °C; 1H NMR (CDCl3, 400 MHz)
d
7.55–7.53 (m, 2H), 7.42–7.32 (m, 3H), 6.48 (s, 1H), 6.33 (s, 1H),