D. Ma and X. Sun
FULL PAPERS
3.70–3.81 (m, 4H), 4.46 (s, 2H), 7.03 (s, 1H), 7.11–7.18 (m, 2H), 7.29–
7.37 (m, 6H), 7.65 (d, J=8.0 Hz, 1H), 7.90 ppm (brs, 1H); 13C NMR
(100 MHz, CDCl3, major isomer): d=10.7, 11.7, 23.1 23.8, 31.9, 37.6,
38.5, 48.7, 51.4, 52.3, 54.5, 66.8, 72.9, 111.4, 112.1, 118.5, 119.0, 121.6,
122.4, 127.3, 127.5, 128.3, 136.3, 138.2, 166.4, 171.5 ppm; HRMS (ESI): m/
z calcd for C28H35N2O4 [M+H]+: 463.2591; found: 463.2585.
Corynantheidol (4)
Compound 17a (50 mg, 0.13 mmol) was dissolved in MeOH (5 mL)
before Pd(OH)2 (5 mg, 10%) and concentrated HCl (1 drop) were
added. The mixture was stirred under a hydrogen atmosphere for 8 h.
The reaction mixture was filtered through a short plug of Celite and then
eluted with MeOH/CH2Cl2 (1:5). The filtrate was concentrated in vacuo
and purified by flash chromatography (methanol/CH2Cl2 1:10) to give 4
as a yellow oil (38 mg, 70%). ½aꢀ2D2:4 =ꢁ10.4 (c=0.50, HCCl3); 1H NMR
(400 MHz, CDCl3): d=0.91 (t, J=7.2 Hz, 3H), 1.25–1.27 (m, 1H), 1.46–
1.59 (m, 5H), 1.88–1.90 (m, 2H), 2.20 (brs, 1H), 2.32 (d, J=11.2 Hz,
1H), 2.50–2.56 (m, 1H), 2.67 (d, J=14.4 Hz, 1H), 2.95–3.03 (m, 3H),
3.16 (d, J=10.0 Hz, 1H), 3.73–3.76 (m, 2H), 7.07 (t, J=7.2 Hz, 1H), 7.12
(t, J=7.2 Hz, 1H), 7.31 (d, J=7.2 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H),
8.14 ppm (brs, 1H); 13C NMR (100 MHz, CDCl3): d=12.8, 17.9, 21.7,
31.8, 36.0, 36.3, 39.7, 53.5, 57.8, 60.5, 60.8, 107.9, 111.0, 118.2, 119.4, 121.3,
127.5, 135.3, 136.2 ppm; HRMS (MALDI/DHB): m/z calcd for
C19H27N2O [M+H]+ 299.2118; found: 299.2117.
Conversion of 14 to 16
NaOH (51 mg, 1.26 mmol) was added to a solution of 14 (193 mg,
0.42 mmol) in THF/MeOH/H2O (4/0.8/1.6 mL) at 08C. The mixture was
stirred at room temperature until the starting material was completely
consumed, as monitored by TLC. After 1n HCl was added to adjust the
pH to less than 5, the resulting mixture was extracted with ethyl acetate
and washed with brine. The organic phase was dried over MgSO4, fil-
tered, and concentrated under reduced pressure. The residue was dis-
solved in toluene (10 mL) and the solution was heated at reflux for 1 h.
The solution was cooled to room temperature and concentrated in vacuo.
The residue was purified by flash chromatography (petroleum/ethyl ace-
23:3
tate=2/1) to give 16 as a colorless oil (165 mg, 98%, d.r.=3:1). ½aꢀD
=
Dihydrocorynantheol (5)
+32.4 (c=1.00, CHCl3); 1H NMR (400 MHz, CDCl3, major isomer): d=
0.75 (t, J=7.2 Hz, 3H), 1.11–1.21 (m, 1H), 1.33–1.40 (m, 2H), 1.46–1.52
(m, 1H), 1.65–1.81 (m, 2H), 2.06 (dd, J=8.0, 17.6 Hz, 1H), 2.53 (dd, J=
5.6, 17.6 Hz, 1H), 2.87 (dd, J=8.0, 12.0 Hz, 1H), 3.03 (t, J=7.2 Hz, 2H),
3.16 (dd, J=4.8, 12.0 Hz, 1H), 3.42–3.53 (m, 2H), 3.57–3.75 (m, 2H),
4.48 (s, 2H), 7.04 (s, 1H), 7.12 (t, J=7.2 Hz, 1H), 7.18 (t, J=7.6 Hz, 1H),
7.28–7.37 (m, 6H), 7.65 (d, J=7.6 Hz, 1H), 7.98 ppm (brs, 1H);
13C NMR (100 MHz, CDCl3, major isomer): d=10.9, 23.2, 23.6, 33.1,
33.4, 36.4, 39.3, 48.2, 51.4, 67.5, 73.1, 111.3, 112.7, 118.7, 119.1, 121.8,
122.2, 127.5, 127.66, 127.68, 128.4, 136.4, 138.3, 169.6 ppm; HRMS (ESI):
m/z calcd for C26H32N2O3Na [M+Na]+: 427.2356; found: 427.2377.
Compound 17b (100 mg, 0.26 mmol) was dissolved in MeOH (10 mL)
before Pd(OH)2 (10 mg, 10%) and concentrated HCl (1 drop) were
added. The mixture was stirred under a hydrogen atmosphere for 8 h.
The reaction mixture was filtered through a short plug of Celite and then
eluted with MeOH/CH2Cl2 (1:5). The filtrate was concentrated in vacuo
and purified by flash chromatography (MeOH/CH2Cl2 1:10) to give 5 as
a yellow solid (77 mg, 70%). ½aꢀ2D6:5 =ꢁ8.7 (c=0.88, CHCl3); 1H NMR
(400 MHz, CDCl3): d=0.85 (t, J=7.2 Hz, 3H), 1.00–1.07 (m, 1H), 1.17–
1.41 (m, 4H), 1.55–1.59 (m, 1H), 1.82–1.87 (m, 2H), 2.13 (d, J=10.4 Hz,
1H), 2.41–2.47 (m, 1H), 2.68 (d, J=10.4 Hz, 1H), 2.88–3.04 (m, 4H),
3.62 (t, J=6.4 Hz, 2H), 7.08 (t, J=7.2 Hz, 1H), 7.12 (t, J=7.2 Hz, 1H),
7.28 (d, J=8.0 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 8.79 ppm (brs, 1H);
13C NMR (100 MHz, CDCl3): d=11.1, 21.5, 23.4, 35.0, 35.4, 37.0, 41.4,
53.0, 59.8, 59.9, 60.1, 107.5, 111.2, 118.2, 119.3, 121.3, 127.3, 134.8,
136.3 ppm; HRMS (MALDI/DHB): m/z calcd for C19H27N2O [M+H]+:
299.2118; found: 299.2116.
Synthesis of 17a and 17b
POCl3 (0.5 mL, 4.0 mmol) was added to
a solution of 16 (200 mg,
0.50 mmol) in toluene (8 mL). The mixture was heated at reflux (for
about 2 h) until the starting material was completely consumed, as moni-
tored by TLC. After being cooled to room temperature, the solution was
concentrated under reduced pressure. After the residue was dissolved in
MeOH (8 mL), NaBH4 (152 mg, 4.0 mmol) was added and the resulting
mixture was stirred at 08C for 1 h. The mixture was extracted with ethyl
acetate and washed with water and brine. The organic layer was dried
over Na2SO4, filtered, and concentrated in vacuo. The residue was puri-
fied by flash chromatography (MeOH/CH2Cl2 1:10) to give 17a (50 mg,
26%) and 17b (120 mg, 62%) as colorless oils.
17a: ½aꢀ2D3:1 =ꢁ2.4 (c=0.90, CHCl3); 1H NMR (400 MHz, CDCl3): d=
0.93 (t, J=7.2 Hz, 3H), 1.27–1.33 (m, 2H), 1.42–1.50 (m, 2H), 1.60–1.78
(m, 4H), 1.81–1.98 (m, 1H), 2.37 (d, J=9.6 Hz, 1H), 2.54–2.61 (m, 1H),
2.69 (d, J=14.4 Hz, 1H), 2.94–3.05 (m, 3H), 3.16 (d, J=10.8 Hz, 1H),
3.59 (t, J=6.4 Hz, 2H), 4.56 (d, J=12.0 Hz, 1H), 4.61 (d, J=12.0 Hz,
1H), 7.10 (t, J=7.2 Hz, 1H), 7.15 (t, J=7.2 Hz, 1H), 7.30 (d, J=8.0 Hz,
1H), 7.40–7.43 (m, 5H), 7.48 (d, J=8.0 Hz, 1H), 7.72 ppm (brs, 1H);
13C NMR (100 MHz, CDCl3): d=12.8, 17.9, 21.9, 32.0, 33.1, 36.8, 39.8,
53.6, 58.1, 60.4, 68.1, 73.0, 108.1, 110.8, 118.2, 119.4, 121.2, 127.6, 127.8,
128.0, 128.6, 135.6, 136.0, 138.7 ppm; HRMS (EI): m/z calcd for
C26H33N2O [M+H]+: 389.2587; found: 389.2594.
17b: ½aꢀ2D3:1 =+12.1 (c=0.98, CHCl3); 1H NMR (400 MHz, CDCl3): d=
0.96 (t, J=7.2 Hz, 3H), 1.15–1.30 (m, 2H), 1.37–1.40 (m, 1H), 1.49–1.51
(m, 2H), 1.68–1.76 (m, 1H), 2.02–2.15 (m, 3H), 2.62 (td, J=11.2, 4.8 Hz,
1H), 2.74 (dd, J=15.2, 3.2 Hz, 1H), 3.00–3.14 (m, 4H), 3.62 (t, J=
6.4 Hz, 2H), 4.51 (d, J=12.0 Hz, 1H), 4.65 (d, J=12.0 Hz, 1H), 7.12 (t,
J=7.2 Hz, 1H), 7.18 (t, J=7.2 Hz, 1H), 7.31 (d, J=7.6 Hz, 1H), 7.39–
7.44 (m, 5H), 7.50 (d, J=7.6 Hz, 1H), 7.70 ppm (brs, 1H); 13C NMR
(100 MHz, CDCl3): d=11.2, 21.8, 23.6, 32.5, 37.3, 42.1, 53.2, 53.6, 59.8,
60.5, 67.6, 72.9, 108.0, 110.8, 118.2, 119.4, 121.3, 127.5, 127.8, 128.1, 128.5,
135.0, 136.0, 138.7 ppm; HRMS (EI): m/z calcd for C26H33N2O [M+H]+:
389.2587; found: 389.2591.
Synthesis of 13
NaBH4 (74 mg, 2.0 mmol) was added in 3 portions to a cooled solution
(ꢁ788C) of 3 (350 mg, 1.00 mmol) in dry MeOH (5 mL). The mixture
was stirred at this temperature for 1 h before 1n HCl (3 mL) was added
to quench the reaction. The solution was warmed to room temperature
and then p-TsOH (50 mg) was added. The resulting mixture was allowed
to stand overnight. The mixture was extracted with ethyl acetate and
washed with water and brine. The organic layer was dried over Na2SO4,
filtered, and concentrated in vacuo. The residue was dissolved in THF/
MeOH/H2O (4/1/2 mL) and then NaOH (80 mg, 2.00 mmol) was added
at 08C. The mixture was stirred at room temperature (overnight) until
the starting material was completely consumed, as monitored by TLC.
After 1n HCl was added to adjust the pH to less than 5, the mixture was
extracted with ethyl acetate and washed with brine. The organic phase
was dried over MgSO4, filtered, and concentrated under reduced pres-
sure. The residue was dissolved in toluene (10 mL) and the solution was
heated at reflux for 1 h. The cooled solution was concentrated in vacuo.
The residue was purified by flash chromatography (petroleum/ethyl ace-
28:2
tate=4:1) to give 13 as a colorless oil (200 mg, 77%, d.r.=8:1). ½aꢀD
=
+15.8 (c=1.06, CHCl3); 1H NMR (400 MHz, CDCl3): d=0.93 (t, J=
7.2 Hz, 3H), 1.31–1.38 (m, 1H), 1.45–1.60 (m, 3H), 1.78–1.86 (m, 1H),
1.88–1.97 (m, 1H), 2.25 (dd, J=7.2, 16.0 Hz, 1H), 2.62 (dd, J=6.8,
16.0 Hz, 1H), 3.50 (t, J=6.0 Hz, 2H), 3.99 (dd, J=7.2, 11.2 Hz, 1H), 4.28
(dd, J=4.4, 11.6 Hz, 1H), 4.48 (s, 2H), 7.28–7.36 ppm (m, 5H); 13C NMR
(100 MHz, CDCl3): d=11.3, 24.3, 33.2, 34.2, 35.3, 40.0, 67.2, 70.5, 73.2,
127.7, 127.8, 128.5, 138.2, 172.7 ppm; HRMS (ESI): m/z calcd for
C16H22O3Na [M+Na]+ 285.1461; found: 285.1474.
Conversion of 13 to 18
A mixture of 13 (55 mg, 0.20 mmol) and 3,4-dimethoxyphenethylamine
(0.24 mL, 1.40 mmol) was heated at 1608C for 6 h. The cooled solution
was diluted with ethyl acetate before it was washed with 1n HCl, saturat-
2162
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Chem. Asian J. 2011, 6, 2158 – 2165