Page 7 of 9
The Journal of Organic Chemistry
123.6, 120.1. 114.8, 114.0, 113.8, 111.9, 111.0, 110.3, 108.7,
1-(3,4-Dimethoxyphenyl)-8,9-dimethoxy-2-(2,4,5-
1
2
3
4
5
6
7
8
104.5, 100.5, 56.3, 56.2, 56.1, 55.9, 55.5, 55.2, 42.4, 28.7.
trimethoxyphenyl)pyrrolo[2,1-a]isoquinoline-3-carboxylic
acid (27). Following the procedure described for the synthesis
of carboxylic acid 23, compound 27 (1.41 g, 2.46 mmol, 100%)
was obtained from ethyl 1-(3,4-dimethoxyphenyl)-8,9-
dimethoxy-2-(2,4,5-trimethoxyphenyl)pyrrolo[2,1-
HRMS (ESI) m/z: [M + H]+ Calcd for C31H30NO8+ 544.1966;
1
Found 544.1961. The H chemical shifts observed for 6 are
within 0.02 ppm of previously reported values, while the 13C
22
chemical shifts are within 0.1 ppm17a,
Information, Table S1).
(See Supporting
a]isoquinoline-3-carboxylate (26) (1.48 g, 2.46 mmol) as a pale
1
brown solid, m.p. 101-106 °C. H NMR (300 MHz, CDCl3, δ):
14-(3,4-Dihydroxyphenyl)-2,3,11,12-tetrahydroxy-8,9-
7.69 (d, J = 7.2 Hz, 1H), 7.54 (s, 1H, CO2H; exchanges with
D2O), 7.19 (s, 1H), 7.00 and 6.98 (overlapping dd and s, J = 7.1,
1,8 Hz, 2H), 6.94–6.89 (m, 2H), 6.72 (s, 1H), 6.63 (d, J = 7.2
Hz, 1H), 6.52 (s, 1H), 3.93 (s, 3H), 3.89 and 3.88 (2 × s, 6H),
3.75 (s, 3H), 3.68 (s, 3H), 3.53 (s, 3H), 3.49 (s, 3H). 13C{1H}
NMR (75 MHz, CDCl3, δ): 151.1, 148.9, 148.5, 147.9, 147.7,
147.6, 142.5, 130.5, 125.3, 124.0, 122.9, 121.8, 120.9, 115.6,
115.3, 114.8, 113.9, 111.3, 110.4, 107.9, 104.7, 97.8, 77.3, 56.4,
56.1, 56.04, 55.99, 55.90, 55.8, 55.3. HRMS (ESI) m/z: [M –
CO2]+ Calcd for C31H32NO7+ 530.2173; Found 530.2166.
dihydro-6H-chromeno[4',3':4,5]pyrrolo-[2,1-a]isoquinolin-6-
one, Lamellarin A4 (3). Neat BBr3 (0.18 mL, ca 10 equiv) was
added to a stirring solution of lamellarin G trimethyl ether (6)
(102 mg, 0.188 mmol) dissolved in CH2Cl2 (50 mL) at room
temperature. The mixture was left to stir for 18 h, after which
time it was quenched with MeOH (1 mL), followed by water
(100 mL). The solution was then extracted with EtOAc (4 × 100
mL), since the polyphenolic lamellarin is poorly soluble in
chlorinated solvents. The combined organic phases were dried
over MgSO4, filtered and solvent was partially removed on a
rotary evaporator until solids began precipitating. Hexane (about
half the volume of the remaining solvent) was added to
complete the crystallization of the products, which were
collected by filtration and dried to give lamellarin A4 (3) (84
mg, 0.183 mmol, 97%) as a white solid, m.p. >300 °C (lit.,22
>300 °C). 1H NMR (400 MHz, DMSO-d6, δ): 9.58 (s, 1H), 9.37
(s, 1H), 9.11 (s, 2H), 8.81 (s, 1H), 8.61 (s, 1H), 6.91 (d, J = 8.0
Hz, 1H), 6.74 (s, 1H), 6.70 and 6.69 (overlapping d and s, J =
2.0 Hz, 2H), 6.63 (dd, J = 8.0, 2.0 Hz, 1H), 6.53 (s, 1H), 6.47 (s,
1H), 4.60 (quintet, J ca 6.8 Hz, 1H), 4.54 (quintet, J ca 6.8 Hz,
1H), 2.95 (br t, J = 6.8 Hz, 2H). 13C{1H} NMR (101 MHz,
DMSO-d6, δ): 154.9, 146.5, 146.4, 146.3, 145.6, 145.1, 144.0,
142.4, 136.4, 127.9, 126.2, 125.8, 121.7, 118.9, 117.9, 117.2,
115.5, 115.1, 113.9, 112.6, 109.7, 109.3, 103.7, 42.4, 28.3.
HRMS (ESI) m/z: [M + H]+ Calcd for C25H18NO8+ 460.1027;
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
14-(3,4-Dimethoxyphenyl)-2,3,11,12-tetramethoxy-6H-
chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one,
Lamellarin D trimethyl ether (7). Following the procedure
described for the synthesis of lamellarin G trimethyl ether (6),
lamellarin D trimethyl ether (7) (1.28 g, 2.36 mmol, 97%) was
obtained from carboxylic acid 27 (1.40 g, 2.44 mmol) as a
25a
1
colorless solid, m.p. 283-284 °C (lit.,22,
278-280 °C). H
NMR (500 MHz, CDCl3, δ): 9.18 (d, J = 7.3 Hz, 1H), 7.24 (dd,
J = 8.0, 1.5 Hz, 1H), 7.19 (d, J = 1.5 Hz, 1H), 7.18–7.14 (m,
2H), 7.07 (s, 1H), 7.02 (d, J = 7.3 Hz, 1H), 6.87 (s, 1H), 6.74 (s,
1H), 4.00 (s, 3H), 3.98 (s, 3H), 3.91 (s, 3H), 3.85 (s, 3H), 3.49
(s, 3H), 3.47 (s, 3H). 13C{1H} NMR (126 MHz, CDCl3, δ):
155.4, 150.1, 150.0, 149.6, 149.2, 149.1, 146.7, 145.5, 134.4,
129.3, 128.3, 124.8, 124.2, 123.3, 119.1, 114.5, 112.3, 112.0,
110.9, 109.9, 107.8, 107.4, 105.3, 105.1, 100.5, 56.3, 56.2,
56.04, 55.97, 55.5, 55.2. HRMS (ESI) m/z: [M + H]+ Calcd for
C31H28NO8+ 542.1809; Found 542.1801. The 1H chemical shifts
observed for 12 are within 0.06 ppm of previously reported
values, while the 13C chemical shifts are within 0.2 ppm22, 25c
(See Supporting Information, Table S3).
1
Found 460.1028. The H chemical shifts observed for 5 are
within 0.04 ppm of previously reported values, while the 13C
24
chemical shifts are within 0.5 ppm22,
Information, Table S2).
(See Supporting
Ethyl
1-(3,4-dimethoxyphenyl)-8,9-dimethoxy-2-(2,4,5-
trimethoxyphenyl)pyrrolo[2,1-a]isoquinoline-3-carboxylate
(26). The saturated pyrrolo[2,1-a]isoquinoline 21 (1.50 g, 2.48
mmol) was dissolved in CH2Cl2 (100 mL), to which was added
DDQ (0.70 g, 3.10 mmol, 1.25 equiv). The solution, which
immediately turned a muddy-brown color, was left to stir at
room temperature for 4 h. Aqueous NaOH solution (2 M, 50
mL) was added, and the phases were separated. The aqueous
phase was re-extracted with CH2Cl2 (2 × 20 mL), and the
combined organic fractions were washed with NaOH solution
(2M, 50 mL), water (50 mL) and brine (50 mL). After drying
over MgSO4, filtration and evaporation in vacuo,
spectroscopically homogeneous 26 (1.49 g, ca 100%) was
14-(3,4-Dihydroxyphenyl)-2,3,11,12-tetrahydroxy-6H-
chromeno[4',3':4,5]pyrrolo[2,1-a]isoquinolin-6-one,
Lamellarin H (5). Following the procedure described for the
synthesis of lamellarin A4 (3), lamellarin H (5) (42 mg, 0.0918
mmol, 98%) was obtained from lamellarin D trimethyl ether (7)
(50 mg, 0.0923 mmol) as a white solid, m.p. >300 °C (lit.,22
1
>300 °C). H NMR (400 MHz, DMSO-d6, δ): 10.04 (s, 1H),
9.81 (s, 1H), 9.47 (s, 1H), 9.26 and 9.25 (2 × s, 2H), 9.05 (d, J =
7.3 Hz, 1H), 8.96 (s, 1H), 7.21 and 7.19 (d, J = 6.0 Hz, and s,
2H), 7.06 (d, J = 7.6 Hz, 1H), 7.02 (s, 1H), 6.87 (s, 1H), 6.86 (d,
J = 2.0 Hz, 1H), 6.78 (dd, J = 7.9, 2.0 Hz, 1H), 6.64 (s, 1H);
13C{1H} NMR (101 MHz, DMSO-d6, δ): 154.9, 148.1, 147.3,
147.0, 146.7, 146.0, 145.7, 142.5, 134.4, 129.3, 125.9, 124.2,
121.9, 121.6, 118.6, 118.0, 117.5, 113.0, 111.87, 111.85, 110.1,
110.0, 109.3, 106.8, 103.8. HRMS (ESI) m/z: [M + H]+ Calcd
1
obtained as a brownish foam, m.p. 95-98 °C. H NMR (500
MHz, CDCl3, δ): 9.32 (d, J = 7.6 Hz, 1H), 7.22 (s, 1H), 7.02 (s,
1H), 6.94 (d, J = 7.6 Hz, 1H), 6.91 (dd, J = 8.2, 1.8 Hz, 1H),
6.87–6.83 and 6.85 (overlapping m and d, J = 8.0 Hz, 2H), 6.64
(br s, 1H), 6.46 (s, 1H), 4.14 (br q, J ca 6 Hz, 2H), 3.96 (s, 3H),
3.88 (s, 3H), 3.86 (s, 3H), 3.71 (s, 3H), 3.68 (s, 3H), 3.61 (br s,
3H), 3.45 (s, 3H), 0.99 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (126
MHz, CDCl3, δ): 162.1, 151.5, 149.2, 148.8, 148.7, 148.6,
147.9, 142.3, 131.9, 130.2, 128.8, 123.8, 123.7, 123.6, 119.8,
118.6, 116.7, 115.9, 114.7, 113.0, 111.9, 110.9, 107.1, 105.3,
97.2, 59.4, 56.5, 56.4, 56.1, 56.0, 55.9, 55.8, 55.3, 14.0. HRMS
(ESI) m/z: [M + H]+ Calcd for C34H36NO9+ 602.2385; Found
602.2372.
1
for C25H16NO8+ 458.0870. Found 458.0865. The H chemical
shifts observed for 5 are within 0.07 ppm of previously reported
values, while the 13C chemical shifts are within 0.5 ppm22, 25c
(See Supporting Information, Table S4).
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