Journal of Natural Products
Article
133.51, 119.73, 110.20, 104.38, 101.54, 100.63, 97.31, 66.33, 60.62,
60.25, 55.96, 40.60, 31.63, 30.89, 26.45, 26.20, 25.15; (+)-HRAPCIMS
m/z 480.2020 [M + H]+ (calcd for C27H29NO7, 480.2022).
Benzo[1,3]dioxol-5-yl-N,N-dimethylethane-1,2-diamine (20a).
Purification: bac chromatography (1:1 CH2Cl2−hexanes) as a light
tan oil, 0.066 g (10%): 1H NMR (CDCl3, 300 MHz) δ 6.56 (1H, d, J =
8.1 Hz), 6.17 (1H, d, J = 2.4 Hz), 6.75 (1H, dd, J1 = 8.1 Hz, J2 = 2.4
Hz), 5.74 (2H, s), 5.84 (2H, s), 3.07 (2H, t, J = 6.0 Hz), 2.53 (2H, t, J
= 6.0 Hz), 2.24 (6H, s); 13C NMR (CDCl3, 125 MHz) δ 148.33,
142.52, 139.85, 108.58, 104.32, 102.33, 100.51, 96.18, 57.90, 44.54;
(+)-HRFABMS m/z 209.1297 [M + H]+ (calcd for C11H16N2O2,
209.1290).
6,7-Methylenedioxy-4-(4-fluorobenzyl)-9-(3,4,5-trimethoxy-
phenyl)-4,9-dihydro-3H-furo[3,4-b]quinolin-1-one (23). Purification:
sgc chromatography (2:1 hexanes−EtOAc → 4:1 EtOAc−hexanes),
light yellow crystals, 0.10 g (46%). Recrystallized from EtOAc and
from EtOAc−hexanes: mp 246−247 °C; 1H NMR (CDCl3, 300
MHz) δ 7.23 (2H, m), 7.06 (2H, m), 6.58 (1H, s), 6.43 (2H, s), 6.40
(1H, s), 5.90 (1H, d, J = 1 Hz), 5.88 (1H, d, J = 1 Hz), 5.06 (1H, s),
4.85 (1H, d, J = 15 Hz), 4.77 (2H, s), 4.76 (1H, d, J = 15 Hz), 3.81
(3H, s) 3.79 (6H, s); 13C NMR (CDCl3, 125 MHz) δ 172.41, 157.60,
153.21, 147.52, 144.37, 141.43, 136.80, 131.77, 130.66, 127.32, 127.25,
118.45, 116.46, 116.29, 110.75, 105.11, 101.61, 98.26, 95.81, 65.05,
60.74, 56.07, 49.08, 40.71; (+)-HRAPCIMS m/z 506.1613 [M + H]+
(calcd for C28H24NO7F, 506.1615); anal. C 66.19; H 5.10; N 2.81%,
calcd for C28H24NO7F: C 66.53; H 4.79; N 2.77%.
6,7-Methylenedioxy-4-(2-dimethyaminoethyl)-9-(3,4,5-
trimethoxyphenyl)-4,9-dihydro-3H-furo[3,4-b]quinolin-1-one (20).
Purification: sgc chromatography (15:1 CH2Cl2−CH3OH) as a light
brown, amorphous solid 0.06 g (52%). Recrystallized from CH3OH:
Benzo[1,3]dioxol-5-yl-(2-pyridin-2-yl-ethyl)-1,2-diamine (24a).
Purification: sgc chromatography (4:1 EtOAc−CH2Cl2), brown oil,
1
1
mp 251−254 °C; H NMR (CDCl3, 300 MHz) δ 6.57 (1H, s), 6.56
0.155 g (14%); H NMR (CDCl3, 300 MHz) δ 8.54 (1H, d, J = 4.5
(1H, s), 6.40 (2H, s), 5.95 (1H, s), 5.94 (1H, s), 4.96 (1H, s), 4.90
(2H, s), 3.78 (9H, s), 3.60 (2H, m), 2.60 (2H, m), 2.29 (6H, s); 13C
NMR (CDCl3, 125 MHz) δ 172.73, 158.03, 153.09, 147.53, 144.07,
141.72, 136.72, 131.27, 118.80, 110.85, 105.16, 101.57, 97.36, 95.01,
65.33, 60.66, 56.04, 45.85, 40.75; (+)-HRAPCIMS m/z 469.1976 [M
+ H]+ (calcd for C25H28N2O7, 469.1975).
Benzo[1,3]dioxol-5-yl-(2-piperidin-1-ylethyl)-1,2-diamine (21a).
Purification: bac chromatography (5:1 EtOAc−CH3OH) as brown
oil, 0.050 g (10%): 1H NMR (CDCl3, 300 MHz) δ 6.65 (1H, d, J = 8.1
Hz), 6.17 (1H, d, J = 2.1 Hz), 5.96 (1H, dd, J1 = 8.1 Hz, J2 = 2.1 Hz),
5.75 (2H, s), 4.20 (1H, bs), 2.99 (2H, t, J = 6.0 Hz), 2.47 (2H, t, J =
6.0 Hz), 2.31 (4H, m), 1.49 (4H, m), 1.36 (2H, m); (+)-HRFABMS
m/z 249.1609 [M + H]+ (calcd for C14H20N2O2, 249.1603).
Hz), 7.58 (1H, dd, J1 = 7.8 Hz, J2 = 1.8 Hz), 7.15 (2H, m,), 6.65 (1H,
d, J = 8.7 Hz), 6.25 (1H, d, J = 2.1 Hz), 6.07 (1H, dd, J1 = 8.7 Hz, J2 =
2.1 Hz), 5.82 (2H, s), 3.93 (1H, bs), 3.45 (2H, t, J = 6.6 Hz), 3.05
(2H, t, J = 6.6 Hz); 13C NMR (CDCl3, 125 MHz) maleate δ 169.18,
156.71, 148.67, 145.26, 145.13, 141.35, 135.22, 134.58, 125.78, 123.66,
112.00, 108.78, 101.62, 101.10, 48.98, 31.58; (+)-HRFABMS m/z
C14H14N2O2, 243.1115 [M + H]+ (calcd for C14H14N2O2, 243.1134).
6,7-Methylenedioxy-4-(2-pyridin-2-ylethyl)-9-(3,4,5-trimethoxy-
phenyl)-4,9-dihydro-3H-furo[3,4-b]quinolin-1-one (24). Purification:
sgc chromatography (30:1 EtOAc−CH3OH), light tan crystals, 0.10 g
1
(39%). Recrystallized from EtOAc−CH3OH: mp 239−241 °C; H
NMR (CDCl3, 300 MHz) δ 8.57 (1H, d, J = 3.9 Hz), 7.56 (1H, dd, J1
= 7.5 Hz, J2 = 2.1 Hz), 7.17 (1H, m), 7.08 (1H, d, J = 7.5 Hz), 6.77
(1H, s), 6.58 (1H, s), 6.37 (2H, s), 5.97 (1H, d, J = 1.8 Hz), 5.96 (1H,
d, J = 1.2 Hz), 4.95 (1H, s), 4.62 (1H, s), 4.61 (1H, s), 4.00 (2H, m),
3.79 (3H, s), 4.77 (6H, s), 3.19 (2H, m); 13C NMR (CDCl3, 125
MHz) δ 172.76, 157.93, 156.95, 152.95, 149.35, 147.52, 144.05,
141.56, 137.01, 136.65, 131.12, 123.77, 122.29, 118.71, 110.75, 105.21,
101.51, 97.06, 95.26, 65.22, 60.56, 56.01, 45.83, 40.53, 35.55;
(+)-HRFABMS m/z 503.1836 [M + H]+ (calcd for C28H26N2O7,
503.1818).
6,7-Methylenedioxy-4-(2-piperidin-1-ylethyl)-9-(3,4,5-trimethoxy-
phenyl)-4,9-dihydro-3H-furo[3,4-b]quinolin-1-one (21). Purification:
sgc chromatography (15:1 CH2Cl2−CH3OH) as a light brown,
amorphous solid, 0.026 g (60%). Recrystallized from EtOAc: mp 170
1
°C (dec); H NMR (CDCl3, 300 MHz) δ 6.58 (1H, s), 6.56 (1H, s),
6.39 (2H, s), 5.95 (1H, s), 5.94 (1H, s), 4.98 (1H, s), 4.93 (2H, s),
3.79 (9H, s), 3.65 (2H, m), 2.61 (2H, t, J = 6.6 Hz), 2.45 (4H, m),
1.57 (4H, m), 1.43 (2H, m); (+)-HRAPCIMS m/z 509.2293 [M +
H]+ (calcd for C28H32N2O7, 509.2288).
Benzo[1,3]dioxol-5-yl-(2-morpholin-4-ylethyl)-1,2-diamine (22a).
Purification: sgc chromatography (100% CH2Cl2), light tan oil, 0.11 g
(10%); 1H NMR (CDCl3, 300 MHz) δ 6.53 (1H, d, J = 8.1 Hz), 6.16
(1H, d, J = 2.1 Hz), 5.94 (1H, dd, J1 = 8.1 Hz, J2 = 2.1 Hz), 5.72 (2H,
s), 3.60 (4H, t, J = 4.5 Hz), 2.98 (2H, t, J = 5.7 Hz), 2.49 (2H, t, J = 6
Hz), 2.34 (4H, m); 13C NMR (CDCl3, 125 MHz) maleate δ 168.55,
148.35, 141.08, 140.74, 134.02, 108.40, 105.10, 100.64, 96.69, 63.57,
55.59, 52.08, 39.11; (+)-HRAPCIMS m/z 251.1392 [M + H]+ (calcd
for C13H18N2O3, 251.1396).
Benzo[1,3]dioxol-5-yl-[2-(4-fluorophenyl)ethyl]-1,2-diamine
(25a). Purification: sgc chromatography (2:1 CH2Cl2−hexanes), light
1
tan oil, 0.28 g (27%); H NMR (CDCl3, 300 MHz) δ 7.06 (2H, m),
6.92 (2H, m), 6.57 (1H, d, J = 8.1 Hz), 6.15 (1H, d, J = 2.1 Hz), 5.96
(1H, dd, J1 = 8.1 Hz, J2 = 2.1 Hz), 5.76 (2H, s), 3.33 (1H, bs), 3.23
(2H, t, J = 6.9 Hz), 2.78 (2H, t, J = 6.9 Hz); 13C NMR (CDCl3, 100
MHz) maleate δ169.67, 148.76, 148.15, 135.47, 130.37, 130.28,
129.99, 116.28, 115.71, 115.50, 108.81, 103.98, 102.13, 53.99, 31.28;
(+)-HRFABMS m/z 260.1077 [M + H]+ (calcd for C15H14NO2F,
260.1087).
6,7-Methylenedioxy-4-(2-morpholin-4-ylethyl)-9-(3,4,5-
trimethoxyphenyl)-4,9-dihydro-3H-furo[3,4-b]quinolin-1-one (22).
Purification: sgc chromatography (9:1 EtOAc−CH3OH) as colorless
crystals, 0.14 g (68%). Recrystallized by slow evaporation from
6,7-Methylenedioxy-4-[2-(4-fluorophenyl)ethyl]-9-(3,4,5-trime-
thoxyphenyl)-4,9-dihydro-3H-furo[3,4-b]quinolin-1-one (25). Purifi-
cation: sgc chromatography (4:1 CH2Cl2−EtOAc) as light yellow,
amorphous solid, 0.07 g (31%). Recrystallized from EtOAc: mp 174−
177 °C; 1H NMR (CDCl3, 300 MHz) δ 7.10 (2H, m), 6.96 (2H, m),
6.66 (1H, s), 6.59 (1H, s), 6.41 (2H, s), 5.98 (1H, s), 5.97 (1H, s),
4.99 (1H, s), 4.35 (1H, d, J = 15.2 Hz), 4.30 (1H, d, J = 15.2 Hz), 3.79
(9H, s), 3.65 (2H, m), 2.99 (2H, t, J = 7.2 Hz); 13C NMR (CDCl3,
125 MHz) δ 172.55, 157.54, 153.16, 147.70, 144.24, 136.97, 133.08,
133.05, 131.18, 130.30, 130.23, 130.14, 118.70, 115.73, 115.64, 111.14,
105.55, 101.69, 97.28, 95.06, 64.98, 60.74, 56.24, 48.35, 40.59, 33.19;
(+)-HRFABMS m/z 520.1808 [M + H]+ (calcd for C29H26NO7F,
520.1772).
1
CH2Cl2−CH3OH: mp 186−189 °C; H NMR (CDCl3, 300 MHz) δ
6.47 (1H, s), 6.45 (1H, s), 6.27 (2H, s), 5.83 (2H, s), 4.85 (1H, s),
4.80 (2H, bs), 3.67 (9H, s), 3.66 (4H, t, J = 4.8 Hz), 3.61 (2H, m),
2.56 (2H, t, J = 6 Hz) 2.40 (4H, m); 13C NMR (CDCl3, 125 MHz) δ
173.28, 158.22, 152.93, 147.52, 144.14, 141.63, 136.58, 130.98, 118.62,
110.75, 105.17, 101.54, 97.19, 94.96, 66.53, 65.43, 60.53, 55.92, 55.70,
53.94, 44.34, 40.49; (+)-HRAPCIMS m/z 511.2082 [M + H]+ (calcd
for C27H30N2O8, 511.2080).
Benzo[1,3]dioxol-5-yl-(4-fluorobenzyl)-1,2-diamine (23a). Purifi-
cation: sgc chromatography (3:1 CH2Cl2−hexanes), light tan oil, 0.14
g (14%); 1H NMR (CDCl3, 300 MHz) δ 7.22 (2H, m), 6.93 (2H, m)
6.55 (1H, d, J = 8.1 Hz), 6.15 (1H, d, J = 2.1 Hz), 5.97 (1H, dd, J1 =
8.1 Hz, J2 = 2.1 Hz), 5.75 (2H, s), 4.13 (2H, s), 3.70 (1H, bs); 13C
NMR (CDCl3, 125 MHz) maleate δ 172.34, 166.85, 164.87, 151.23,
150.17, 138.09, 135.05, 134.98, 132.60, 129.31, 118.73, 118.60, 118.43,
111.26, 106.49, 104.65, 57.63; (+)-HRFABMS m/z 246.0920 [M +
H]+ (calcd for C14H12NO2F, 246.0930).
Benzo[1,3]dioxol-5-yl-[2-(4-chlorophenyl)ethyl]-1,2-diamine
(26a). Purification: sgc chromatography (100% CH2Cl2), light tan oil,
1
0.063 g (10%); H NMR (CDCl3, 300 MHz) δ 7.26 (2H, m), 7.13
(2H, m), 6.65 (1H, d, J = 8.4 Hz), 6.23 (1H, d, J = 2.1 Hz), 5.96 (1H,
dd, J1 = 8.4 Hz, J2 = 2.1 Hz), 5.85 (2H, s), 3.44 (1H, bs), 3.31 (2H, t, J
= 6.6 Hz), 2.86 (2H, t, J = 6.6 Hz); 13C NMR (CDCl3, 125 MHz)
maleate δ 170.61, 151.44, 150.77, 138.22, 137.38, 135.67, 132.85,
132.78, 131.58, 118.87, 111.50, 106.61, 104.81, 56.37, 34.18;
H
J. Nat. Prod. XXXX, XXX, XXX−XXX