Jolicoeur and Lubell
217
EtOAc–hexane) afforded bipyrrole 20b as a grey solid
(127 mg) in 59% yield; mp 155 °C. H NMR (400 MHz,
General procedure for the synthesis of 2,2′-bipyrroles
(19) (method C)
1
(CD3)2CO) δ: 10.14 (br s, 1H), 9.59 (br s, 1H), 7.46 (d, J =
7.2 Hz, 2H), 7.38 (t, J = 7.1 Hz, 2H), 7.31 (t, J = 7.2 Hz,
1H), 6.73 (s, 1H), 6.38 (s, 1H), 6.28 (s, 1H), 6.09 (m, 2H),
4.94 (s, 2H). 13C NMR (100 MHz, (CD3)2CO) δ: 149.1,
138.9, 128.7, 128.0, 127.9, 126.9, 124.9, 117.5, 109.0,
103.4, 100.0, 93.5, 72.5. HR-MS calcd. for C15H15N2O ([M
+ H+]): 239.1179; found: 239.1189.
4-(Methoxy)-1-benzenesulfonyl-2,2′-bipyrrole (19a)
Ammonium formate (711 mg, 11.3 mmol) was added to a
solution of 4-(4-methoxy-1-(phenylsulfonyl)-1H-pyrrol-2-
yl)-4-oxobutanal (17a) (362 mg, 1.13 mmol) in EtOH–
MeCN–AcOH (50 mL–5 mL–50 µL). After stirring for 18 h,
the reaction was treated with water followed by EtOAc. The
layers were separated and the aqueous layer was extracted
with EtOAc. The organic layers were combined, washed
with brine, dried (MgSO4), and concentrated to a residue
that was purified by filtration on silica gel (30% EtOAc–
hexane). Evaporation of the collected fractions yielded
General procedure for the synthesis of
undecylprodigiosins (method E)
4-Methoxy-5-[(5-undecyl-2H-pyrrol-2-ylidene)methyl]-2,2′-
bi-1H-pyrrole hydrochloride (undecylprodigiosin
1
bipyrrole 19a as a dark oil (318 mg) in 93% yield. H NMR
(400 MHz, CDCl3) δ: 9.10 (br s, 1H), 7.50 (t, J = 7.3 Hz,
1H), 7.36 (m, 4H), 6.90 (m, 1H), 6.82 (d, J = 2.1 Hz, 1H),
6.16 (m, 1H), 6.07 (m, 1H), 6.02 (d, J = 2.1 Hz, 1H), 3.73
(s, 3H). 13C NMR (100 MHz, CDCl3) δ: 150.8, 137.4, 133.7,
128.8, 127.8, 126.8, 121.1, 119.3, 110.9, 108.7, 107.9,
102.6, 57.6. HR-MS calcd. for C15H15N2O3S ([M + H+]):
303.0798; found: 303.0796.
hydrochloride)
A solution of 4-(methoxy)-2,2′-bipyrrole 20a (26.4 mg,
0.163 mmol) and 5-undecylpyrrole-2-carboxaldehyde 21
(44.6 mg, 0.179 mmol) in EtOH (4 mL) was warmed to
50 °C, and treated with concentrated hydrobromic acid
(10 µL). The heating bath was removed and the reaction
mixture was allowed to cool to room temperature while stir-
ring for 15 h. The reaction mixture was concentrated in
vacuo. Chromatography on neutral aluminium oxide (0%–
10% EtOAc–hexane) and evaporation of the collected frac-
tions afforded the free base, which was treated with HCl in
ether (1 mol/L, 3 mL) and freeze dried to afford unde-
cylprodigiosin hydrochloride as a red film (52 mg) in 75%
4-(Benzyloxy)-1-benzenesulfonyl-2,2′-bipyrrole (19b)
The title compound was prepared according to method C
from pyrrole 17b (1.16 mmol). Purification by filtration on
silica gel (25% EtOAc–hexane) afforded bipyrrole 19b as a
1
grey solid (355 mg) in 81% yield; mp 107 °C. H NMR
(400 MHz, CDCl3) δ: 9.10 (br s, 1H), 7.40 (m, 10H), 6.90
(m, 1H), 6.87 (d, J = 2.0 Hz, 1H), 6.17 (m, 1H), 6.09 (m,
2H), 4.95 (s, 2H). 13C NMR (100 MHz, CDCl3) δ: 149.5,
137.2, 136.3, 133.6, 128.8, 128.5, 128.1, 127.7, 127.6,
126.8, 121.1, 119.3, 110.9, 108.7, 108.3, 103.8, 72.2. HR-
MS calcd. for C21H19N2O3S ([M + H+]): 379.1111; found:
379.1121.
1
yield. H NMR (400 MHz, CDCl3) δ: 12.5–11.7 (br s, 1H),
10.9–10.0 (br s, 1H), 6.91 (s, 1H), 6.71 (d, J = 3.5 Hz, 1H),
6.64 (s, 1H), 6.51 (d, J = 3.5 Hz, 1H), 6.14 (m, 2H), 5.86 (d,
J = 3.5 Hz, 1H), 4.00 (s, 3H), 2.08 (t, J = 6.2 Hz, 2H), 1.4–
1.1 (m, 18H), 0.95 (t, J = 6.6 Hz, 3H). 13C NMR (100 MHz,
CDCl3) δ: 169.0, 160.2, 144.8, 128.2, 128.1, 123.0, 121.2,
116.0, 112.9, 109.9, 109.2, 108.5, 95.7, 58.3, 31.9, 29.63,
29.59, 29.47, 29.33, 29.23, 29.15, 29.0, 27.2, 22.7, 14.1.
HR-MS calcd. for C25H36N3O ([M + H+]): 394.2857; found:
394.2853.
General procedure for the synthesis of 2,2′-bipyrroles
(20) (method D)
1
Ref. 15: H NMR (400 MHz, CDCl3) δ: 0.9 (m, 3H), 1.1–
4-(Methoxy)-2,2′-bipyrrole (20a)
1.5 (m, 16H), 1.8 (m, 2H), 2.95 (t, J = 7.5 Hz, 2H), 4.05 (s,
3H), 6.0 (d, J = 1.8 Hz, 1H), 6.2 (dd, J = 1.8, 3.9 Hz, 1H),
6.5 (m, 1H), 6.85 (dd, J = 3.9, 2.6 Hz, 1H), 7.0 (m, 1H),
7.05 (s, 1H), 7.25 (m, 1H), 12.5–12.7 (2 bs, 2H), 12.9 (bs,
1H).
Magnesium powder (255 mg, 10.5 mmol) was added to a
solution of 4-(methoxy)-1-benzenesulfonyl-2,2′-bipyrrole
(19a) (318 mg, 1.05 mmol) in methanol (20 mL). After stir-
ring for 18 h, the reaction was treated with a solution of sat-
urated aqueous NH4Cl followed by EtOAc. The layers were
separated and the aqueous layer was extracted with EtOAc.
The organic layers were combined, washed with brine, dried
(MgSO4), and concentrated to a residue that was purified by
chromatography over neutral aluminium oxide (10%–30%
EtOAc–hexane). Evaporation of the collected fractions
yielded bipyrrole 20a as a grey solid (92 mg) in 54% yield;
1
Ref. 44: H NMR (CDCl3) τ: 2.83 (br, 3H), 2.78 (m, 1H),
3.06 (s, 1H), 3.10 (m, 2H), 3.67 (m, 1H), 3.80 (m, 1H), 3.96
(d, 1H), 6.05 (s, 3H), 7.06 (t, 2H), 8.76 (m, 18H), 9.13 (t,
3H).
4-Benzyloxy-5-[(5-undecyl-2H-pyrrol-2-ylidene)methyl]-
2,2′-bi-1H-pyrrole hydrochloride (PNU-156804)
The title compound was prepared according to method E
from bipyrrole 20b (0.090 mmol) to afford PNU-156804 hy-
1
mp 143 °C. H NMR (400 MHz, CDCl3) δ: 8.24 (br s, 1H),
7.66 (br s, 1H), 6.76 (s, 1H), 6.30 (s, 1H), 6.23 (s, 1H), 6.22
(s, 1H), 5.94 (s, 1H), 3.75 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 149.8, 125.8, 124.2, 117.7, 109.4, 103.7, 98.8,
93.4, 57.9. HR-MS calcd. for C9H11N2O ([M + H+]):
163.0869; found: 163.0866.
1
drochloride as a red film (37 mg) in 83% yield. H NMR
(400 MHz, CDCl3) δ: 13.0–11.6 (br s, 1H), 11.0–9.7 (br s,
1H), 7.56 (d, J = 7.2 Hz, 2H), 7.49 (t, J = 7.0 Hz, 2H), 7.44
(t, J = 7.2 Hz, 1H), 6.99 (s, 1H), 6.72 (d, J = 3.4 Hz, 1H),
6.66 (s, 1H), 6.51 (d, J = 3.6 Hz, 1H), 6.23 (s, 1H), 6.15 (t,
J = 3.2 Hz, 1H), 5.87 (d, J = 3.6 Hz, 1H), 5.21 (s, 2H), 2.09
(t, J = 7.3 Hz, 2H), 1.40–1.15 (m, 18H), 0.93 (t, J = 6.6 Hz,
3H). 13C NMR (100 MHz, CDCl3) δ: 167.8, 160.0, 145.0,
4-(Benzyloxy)-2,2′-bipyrrole (20b)
The title compound was prepared according to method D
from bipyrrole 19b (0.905 mmol). Purification by column
chromatography on neutral aluminium oxide (10%–25%
© 2008 NRC Canada