Synthesis of the Core Structure of Dictyodendrin
1771
3.55 (3H, s, –OCH2OCH3), 3.57 (3H, s, –CO2CH3), 4.42–4.49 (1H, m,
–CH(CH3)2), 4.48–4.55 (1H, m, –CH(CH3)2), 4.90 (2H, t, J ¼ 8:0 Hz,
NCH2CH2Ar), 5.30 (2H, s, –OCH2OCH3), 5.59 (2H, s, NCH2O), 6.62
(1H, s, 20000-H), 6.65 (2H, d, J ¼ 8:4 Hz, 30- and 50-Hs), 6.81–6.87 (3H,
m, 3000-H, 5000-H and 60000-H), 6.89–6.95 (4H, m, 2000-H, 6000-H, 4000-H and
5000-H), 7.19 (2H, d, J ¼ 8:4 Hz, 20- and 60-Hs). Anal. Calcd. for
C44H56N2O9Si: C, 67.32; H, 7.19; N, 3.57%. Found: C, 67.13; H, 7.42;
N, 3.32%.
3-(4-Isopropoxypheyl)-1-[2-(4-isopropoxyphenyl)ethyl]-4-[7-me-
thoxymethoxy-1-(2-trimethylsilanylethoxymethyl)-indol-3-yl]pyrrole-
2,5-dicarboxylic acid bis-(4,6-dimethoxy-1,3,5-triazin-2-yl) ester (28).
To a solution of diacid 24a (1.0670 g, 1.4095 mmol), and 2-chloro-4,6-
dimethoxy-1,3,5-triazine (0.5688 mg, 3.2397 mmol) in dry THF
(15 ml) was added dropwise N-methylmorpholine (1.55 ml, 14.1
mmol), and the mixture was stirred at room temperature for 19.5 h.
The mixture was then diluted with ether, successively washed with
cold 1 M aqueous HCl and 5% aqueous NaHCO3, dried over Na2SO4,
and concentrated in vacuo. The residue was chromatographed on silica
gel eluted with hexane/EtOAc (1:1) to give 28 (1.0147 g, 0.9802
mmol, 70%) as a yellow amorphous solid. IR ꢁmax (KBr) cmꢀ1: 2976,
1755 (C=O), 1728 (C=O), 1581, 1469, 1366, 1243 (SiCH3), 1124
(C–O–C), 835, 815. NMR ꢂH (400 MHz): ꢀ0:11 (9H, s,; –Si(CH3)3),
0.73 (2H, t, J ¼ 8:0 Hz, –CH2CH2SiMe3), 1.20 (6H, d, J ¼ 6:0 Hz,
–CH(CH3)2), 1.32 (6H, d, J ¼ 6:0 Hz, –C(CH3)2), 3.15–3.31 (4H,
m, NCH2CH2Ar and –CH2CH2SiMe3), 3.52 (3H, s, –OCH2OCH3),
3.87 (6H, s, ArOCH3), 3.99 (6H, s, ArOCH3), 4.31–4.39 (1H, m,
–CH(CH3)2), 4.48–4.55 (1H, m, –CH(CH3)2), 4.98 (2H, t, J ¼ 8:0 Hz,
NCH2CH2Ar), 5.24 (2H, s, –OCH2OCH3), 5.58 (2H, s, NCH2O), 6.53
(2H, d, J ¼ 8:4 Hz, 30- and 50-Hs), 6.76 (1H, t, J ¼ 7:2 Hz, 50000-H),
6.79–6.85 (5H, m, 3000-, 5000-, 20000-, 40000- and 60000-Hs), 6.98 (2H, d,
J ¼ 8:4 Hz, 2000- and 6000-Hs), 7.29 (2H, d, J ¼ 8:4 Hz, 3000- and 6000-Hs).
Anal. Calcd. for C52H62N8O13Si: C, 60.33; H, 6.04; N, 10.82%. Found:
C, 59.99; H, 6.10; N, 10.54%.
Dimethyl 4-[1-benzyloxymethyl-7-methoxymethoxyindol-3-yl]-3-(4-
isopropoxyphenyl)-1-[2-(4-isopropoxyphenyl)ethyl]pyrrole-2,5-dicar-
boxylate (8b). White crystals, mp 117–118 ꢁC. IR ꢁmax (KBr) cmꢀ1
:
1722 (C=O), 1711 (C=O), 1435, 1243, 1209, 1164 (C–O–C), 1105,
1040 (C–O–C), 950, 731. NMR ꢂH (400 MHz): 1.18 (6H, d,
J ¼ 6:0 Hz, –CH(CH3)2), 1.31 (6H, d, J ¼ 6:0 Hz, –C(CH3)2), 3.12
(2H, t, J ¼ 8:0 Hz, NCH2CH2Ar), 3.35 (3H, s, –CO2CH3), 3.50 (3H, s,
–OCH2OCH3), 3.58 (3H, s, –CO2CH3), 4.09 (2H, s, –OCH2Ph), 4.26–
4.34 (1H, m, –CH(CH3)2), 4.47–4.50 (1H, m, –CH(CH3)2), 4.91 (2H, t,
J ¼ 8:0 Hz, NCH2CH2Ar), 5.27 (2H, s, –OCH2OCH3), 5.67 (2H, s,
NCH2O), 6.63 (1H, s, 20-H), 6.64 (2H, d, J ¼ 8:4 Hz, 30000- and 50000-Hs),
6.83 (2H, d, J ¼ 8:4 Hz, 3000- and 5000-Hs), 6.88 (1H, t, J ¼ 4:4 Hz,
50-H), 6.95 (2H, d, J ¼ 8:4 Hz, 2000- and 6000-Hs), 6.96–7.00 (2H, m,
40- and 60-Hs), 7.09–7.14 (2H, m, Ph-Hs), 7.19 (2H, d, J ¼ 8:4 Hz, 20000
-
and 60000-Hs), 7.24–7.32 (3H, m, Ph-Hs). Anal. Calcd. for C46H50N2O9:
C, 71.30; H, 6.50; N, 3.62%. Found: C, 71.00; H, 6.58; N, 3.44%.
3-(4-Isopropoxyphenyl)-1-[2-(4-isopropoxyphenyl)ethyl]-2,5-bis-
(4-methoxybenzoyl)-4-[7-methoxymethoxy-1-(2-trimethylsilanylethoxy-
methyl)-indol-3-yl]pyrrole (29). To a solution of activated ester 28
(711.1 mg, 0.6869 mmol) in dry ether (15 ml) was added dropwise a
0.5 M THF solution of 4-methoxyphenylmagnesium bromide (3.00 ml,
1.50 mmol) at ꢀ20 ꢁC under an Ar atmosphere, and the whole was
stirred at the same temperature for 1.5 h. The reaction was then
quenched with 10% aqueous NH4Cl, and the mixture was extracted
twice with ether. The combined ethereal extract was washed with
brine, dried over Na2SO4, and concentrated in vacuo. The residue was
chromatographed on silica gel eluted with hexane/EtOAc (5:1) to give
29 (488.4 mg, 0.5211 mmol, 76%) as a pale yellow amorphous powder.
IR ꢁmax (KBr) cmꢀ1: 2974, 1598 (C=O), 1510, 1249 (SiCH3), 1163
(C–O–C), 985, 835. NMR ꢂH (400 MHz): ꢀ0:08 (9H, s, –Si(CH3)3),
0.76 (2H, t, J ¼ 8:0 Hz, –CH2CH2SiMe3), 1.13 (6H, d, J ¼ 6:0 Hz,
–CH(CH3)2), 1.27 (6H, d, J ¼ 6:0 Hz, –C(CH3)2), 3.02 (2H, t,
J ¼ 8:0 Hz, NCH2CH2Ar), 3.20 (2H, t, J ¼ 8:0 Hz, –CH2CH2SiMe3),
3.46 (3H, s, –OCH2OCH3), 3.63 (3H, s, ArOCH3), 3.71 (3H, s,
ArOCH3), 4.24–4.32 (1H, m, –CH(CH3)2), 4.38–4.46 (1H, m,
–CH(CH3)2), 4.58 (2H, t, J ¼ 8:0 Hz, NCH2CH2Ar), 5.19 (2H, s,
–OCH2OCH3), 5.45 (2H, s, NCH2O), 6.36 (2H, d, J ¼ 8:4 Hz, 30000- and
50000-Hs), 6.43 (2H, d, J ¼ 8:4 Hz, 300000- and 500000-Hs), 6.59 (2H, d,
J ¼ 8:4 Hz, 30- and 50-Hs), 6.66–6.76 (6H, m, 3000-, 5000-, 2000000-, 4000000-,
5000000- and 6000000-Hs), 6.80 (2H, d, J ¼ 8:4 Hz, 2000- and 6000-Hs), 7.11 (2H,
d, J ¼ 8:4 Hz, 20- and 60-Hs), 7.56 (2H, d, J ¼ 8:4 Hz, 20000- and
60000-Hs), 7.61 (2H, d, J ¼ 8:4 Hz, 200000- and 600000-Hs). Anal. Calcd. for
C56H64N2O9Si: C, 71.77; H, 6.88; N, 2.99%. Found: C, 71.42; H, 6.88;
N, 2.74%.
Dimethyl 4-[1-tert-butoxycarbonyl-7-diphenylmethoxyindol-3-yl]-
3-(4-isopropoxyphenyl)-1-[2-(4-isopropoxyphenyl)ethyl]pyrrole-2,5-
dicarboxylate (8c). White crystals, mp 75–76 ꢁC. IR ꢁmax (KBr) cmꢀ1
:
1754 (C=O), 1711 (C=O), 1302, 1235, 1152 (C–O–C), 1046 (C–O–
C), 957, 704. NMR ꢂH (400 MHz): 1.29 (6H, d, J ¼ 6:0 Hz,
–CH(CH3)2), 1.31 (6H, d, J ¼ 6:0 Hz, –C(CH3)2), 1.52 (9H, s,
–OC(CH3)3), 3.10 (2H, t, J ¼ 7:6 Hz, NCH2CH2Ar), 3.31 (3H, s,
–CO2CH3), 3.57 (3H, s, –CO2CH3), 4.41–4.54 (2H, m,
–CH(CH3)2 ꢂ 2), 4.89 (2H, t, J ¼ 7:6 Hz, NCH2CH2Ar), 6.25 (1H,
s, –CHPh2), 6.64 (1H, d, J ¼ 8:0 Hz, 40-H), 6.69 (2H, d, J ¼ 8:4 Hz,
300- and 500-Hs), 6.76 (1H, d, J ¼ 8:0 Hz, 60-H), 6.82 (2H, d,
J ¼ 8:4 Hz, 30000- and 50000-Hs), 6.88 (1H, s, 20-H), 6.91 (1H, t,
J ¼ 8:0 Hz, 50-H), 6.92 (2H, d, J ¼ 8:4 Hz, 20000- and 60000-Hs), 7.17
(2H, d, J ¼ 8:4 Hz, 200- and 600-Hs), 7.19–7.25 (2H, m, Ph-Hs), 7.26–
7.33 (4H, m, Ph-Hs), 7.61–7.67 (4H, m, Ph-Hs). Anal. Calcd. for
C54H56N2O9: C, 73.95; H, 6.44; N, 3.19%. Found: C, 73.72; H, 6.54;
N, 3.04%.
3-(4-Isopropoxyphenyl)-1-[2-(4-isopropoxyphenyl)ethyl]-4-[7-me-
thoxymethoxy-1-(2-trimethylsilanylethoxymethyl)-indol-3-yl]pyrrole-
2,5-dicarboxylic acid (24a).
A solution of diester 8a (1.40 g,
1.79 mmol) in a mixture of 3 M aqueous NaOH (30 ml) and EtOH
(30 ml) was stirred vigorously at 90 ꢁC for 17 h. The reaction mixture
was cooled to room temperature and concentrated in vacuo. The
residue was diluted with cold water, and the pH was adjusted to 2–3
with 3 M aqueous HCl while cooling in an ice-water bath. The
precipitated diacid was extracted twice with EtOAc, and the combined
organic layers were washed with brine. After drying (Na2SO4) and
removing the solvent, the solid residue was chromatographed on silica
gel eluted with hexane/EtOAc (1:1) to give 24a (1.28 g, 1.69 mmol,
95%) as pale yellow crystals. An analytical sample was obtained by
recrystallization from EtOH/hexane (1:1) as white crystals, mp 155 ꢁC.
IR ꢁmax (KBr) cmꢀ1: 2977 (OH), 1691 (C=O), 1659 (C=O), 1430,
1244 (SiCH3), 1105 (C–O–C), 1078 (C–O–C), 835, 735. NMR ꢂH
(400 MHz): ꢀ0:09 (9H, s, –Si(CH3)3), 0.76 (2H, t, J ¼ 8:0 Hz,
–CH2CH2SiMe3), 1.26 (6H, d, J ¼ 6:0 Hz, –CH(CH3)2), 1.30 (6H, d,
J ¼ 6:0 Hz, –C(CH3)2), 3.09 (2H, t, J ¼ 7:2 Hz, NCH2CH2Ar), 3.25
(2H, t, J ¼ 8:0 Hz, –CH2CH2 SiMe3), 3.53 (3H, s, –OCH2OCH3),
4.39–4.46 (1H, m, –CH(CH3)2), 4.46–4.53 (1H, m, –CH(CH3)2), 4.99
(2H, t, J ¼ 7:2 Hz, NCH2CH2Ar), 5.28 (2H, s, –OCH2OCH3), 5.63
(2H, s, NCH2O), 6.64 (2H, d, J ¼ 8:4 Hz, 30- and 50-Hs), 6.78 (2H, d,
J ¼ 8:4 Hz, 3000- and 5000-Hs), 6.80 (1H, s, 20000-H), 6.88 (1H, dd,
J ¼ 2:0, 6.8 Hz, 60000-H), 6.93–7.00 (4H, m, 2000-, 6000-, 40000- and 50000-Hs),
7.11 (2H, d, J ¼ 8:4 Hz, 20- and 60-Hs). Anal. Calcd. for
C42H52N2O9Si: C, 66.64; H, 6.92; N, 3.70%. Found: C, 66.52; H,
7.02; N, 3.47%.
4-[2-Cyanomethyl-7-methoxymethoxy-1-(2-trimethylsilanylethoxy-
methyl)-indol-3-yl]-3-(4-isopropoxyphenyl)-1-[2-(4-isopropoxyphenyl)-
ethyl]-2,5-bis-(4-methoxybenzoyl) pyrrole (6b). To a refluxing de-
gassed solution of 29 (30.1 mg, 32.1 mmol) and EtO(C=S)SCH2CN
(19.4 mg, 120.0 mmol), which had been prepared by the reaction of
EtONa, CS2 and ClCH2CN in EtOH by a standard procedure, in dry
1,2-dichloroethane (1.0 ml), a solution of dilauroyl peroxide (47.8 mg,
120.0 mmol) in dry 1,2-dichloroethane (0.5 ml) was dropwise added
over a period of 5.5 h via a syringe pump. The solution was further
refluxed for 2 h and concentrated in vacuo. The crude product
was chromatographed on silica gel eluted with toluene/EtOAc (19:1)
to afford 6b (11.1 mg, 1.14 mmol, 36%) as a yellow amorphous
powder. IR ꢁmax (KBr) cmꢀ1: 2974, 2252 (CꢃN), 1594 (C=O),
1510, 1251 (SiCH3), 1164 (C–O–C), 1107, 1075, 983, 836, 767. NMR
ꢂH (400 MHz): ꢀ0:08 (9H, s, Si(CH3)3), 0.68–0.83 (2H, m,
–CH2CH2SiMe3), 1.13 (3H, d, J ¼ 6:0 Hz, –CH(CH3)(CH3)), 1.15
(3H, d, J ¼ 6:0 Hz, –CH(CH3)(CH3)), 1.27 (3H, d, J ¼ 6:0 Hz,
–CH(CH3)(CH3)), 1.28 (3H, d, J ¼ 6:0 Hz, –CH(CH3)(CH3)), 2.87–