chromatography (4 : 1 hexanes/EtOAc) and recrystallized from
ethanol for characterization purposes. trans-Indolelactone: 1H
NMR (CDCl3, 400 MHz) d 7.81 (s, 1H), 7.27–7.29 (m, 1H), 7.20
(td, J = 7.0, 1.1 Hz, 1H), 7.15 (td, J = 7.4, 1.5 Hz, 1H), 4.47 (s,
1H), 3.85 (s, 3H), 3.63 (s, 3H), 2.56 (s, 3H), 2.25 (s, 3H), 1.80 (s,
3H), 1.70 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 171.3, 168.8,
154.0, 136.8, 132.9, 124.8, 121.1, 120.7, 119.7, 118.9, 114.7, 109.0,
82.8, 56.7, 52.2, 29.2, 25.3, 24.3, 20.3, 11.5. C20H23NO4 MS (APCI)
m/z: 342.1713 [obtained M + H]+, 342.1700 [calculated M + H]+.
cis-Indolelactone as a mixture of atropisomers, approximately 2 : 1
ratio: 1H NMR (CDCl3, 400 MHz) d 8.14 (d, J = 7.8 Hz, 0.3H),
7.52 (d, J = 7.8 Hz, 0.7H), 7.17–7.23 (m, 1H), 7.13 (t, J = 7.8 Hz,
1H), 7.06 (t, J = 7.1 Hz, 1H), 4.27 (s, 0.7H), 4.11 (s, 0.3H), 3.63 (s,
3H), 3.01 (s, 2H), 2.87 (s, 1H), 2.58 (s, 2H), 2.43 (s, 1H), 2.37 (s, 3H),
1.96 (s, 3H), 1.88 (s, 2H), 1.78 (s, 1H); 13C NMR (CDCl3, 100 MHz)
d 170.5, 170.4, 168.3, 168.0, 154.0, 153.2, 136.8, 136.2, 134.0, 131.2,
125.9, 124.5, 122.3, 120.9, 120.7, 120.6, 120.5, 119.7, 119.4, 118.9,
111.5, 109.8, 108.8, 108.1, 84.2, 83.4, 58.6, 57.7, 51.4, 51.2, 30.1,
30.0, 29.4, 29.3, 24.3, 20.4, 20.3, 12.7, 11.8. C20H23NO4 MS (APCI)
m/z: 342.1714 [obtained M + H]+, 342.1700 [calculated M + H]+.
was allowed to stir overnight and then concentrated in vacuo. The
residue was quenched with 50 mL of water and extracted with
EtOAc (3 ¥ 35 mL). The aqueous layer was acidified with 0.5 M
HCl to pH 1 and extracted with EtOAc (3 ¥ 35 mL). The combined
organic layers were dried over MgSO4, filtered, and concentrated
in vacuo. Trituration with CHCl3 provided 0.11 g (39%) of the
amide acid ester 10. 1H NMR (CD3OD, 400 MHz) d 7.34 (d, J =
7.9 Hz, 1H), 7.24 (d, J = 8.1 Hz, 1H), 7.06 (td, J = 7.5, 1.0 Hz,
1H), 6.95 (td, J = 7.5, 0.7 Hz, 1H), 4.09 (d, J = 17.5 Hz, 1H), 4.01
(d, J = 17.6 Hz, 1H), 3.75 (s, 3H), 3.63 (s, 3H), 2.33 (s, 3H), 2.16
(s, 3H), 1.87 (s, 3H), 1.85 (s, 3H); 13C NMR (CD3OD, 100 MHz) d
172.9, 171.9, 171.1, 149.1, 143.1, 138.5, 135.4, 133.8, 128.4, 127.5,
121.7, 120.1, 120.1, 114.9, 109.8, 52.6, 42.2, 29.7, 24.3, 22.5, 22.3,
11.4. C22H26N2O5 MS (APCI) m/z: 399.1927 [obtained M + H]+,
399.1914 [calculated M + H]+.
Synthesis of amide diacid 11
NaOH (0.1 g, 2.50 mmol) was added to the amide acid ester 10
(0.11 g, 0.28 mmol) in 100 mL of methanol and stirred at room
temperature overnight. The solution was concentrated in vacuo.
The resulting white precipitate was dissolved in 25 mL of Na2CO3
(0.19 M) and extracted with EtOAc (2 ¥ 25 mL). The aqueous
layer was carefully acidified with concentrated HCl to pH 1 and
extracted with EtOAc (3 ¥ 25 mL). The combined organic layers
were dried over MgSO4, filtered, and concentrated in vacuo. A
trituration was performed using chloroform to yield 0.09 g (85%)
of amide diacid 11. 1H NMR (CD3OD, 400 MHz) d 7.34 (d, J =
7.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 1H), 7.06 (td, J = 7.6, 1.0 Hz,
1H), 6.95 (td, J = 7.4, 1.0 Hz, 1H), 4.06 (d, J = 17.6 Hz, 1H), 4.00
(d, J = 17.8 Hz, 1H), 3.62 (s, 3H), 2.33 (s, 3H), 2.15 (s, 3H), 1.86 (s,
3H), 1.84 (s, 3H); 13C NMR (CD3OD, 100 MHz) d 173.0, 172.8,
171.1, 149.0, 142.9, 138.5, 135.3, 133.9, 128.4, 127.5, 121.7, 120.1,
120.0, 114.8, 109.8, 42.2, 29.7, 24.2, 22.5, 22.3, 11.4. C21H24N2O5
MS (ESI) m/z: 407.1585 [obtained M + Na]+, 407.1577 [calculated
M + Na]+.
Synthesis of methyl indolylfulgide 918,19
Sodium hydride (60% dispersion in oil, 0.28 g, 7.00 mmol) was
added to a mixture of cis/trans indolelactones 8 (1.0 g, 2.90 mmol)
in 100 mL of DMF at 0 ◦C. The mixture was warmed to room
temperature and left to react for 1 h. The reaction mixture was
cooled back again to 0 ◦C, and H2O (1.05 mL, 58 mmol) was
added. Hydrogen gas evolved, and the reaction was left to react
overnight. The mixture was concentrated in vacuo and yielded
a white solid. The white solid was then dissolved in 100 mL
of water and extracted with ethyl acetate (3 ¥ 100 mL). The
aqueous layer was acidified with concentrated HCl to pH 2 and
extracted with ethyl acetate (3 ¥ 100 mL). The combined organic
layers were dried over MgSO4, filtered, and concentrated in vacuo.
The resulting crude diacid was suspended in 15 mL of toluene.
Acetic anhydride (15 mL, 0.16 mol) was added, and the reaction
mixture was refluxed for 2 h under argon gas. The solution was
then concentrated in vacuo. The residue was partitioned between
100 mL of water and 30 mL CH2Cl2, and then the aqueous layer
was extracted with CH2Cl2 (2 ¥ 30 mL). The combined organic
layers were dried over MgSO4, filtered, and concentrated in vacuo.
Purification was performed via silica gel chromatography with
CH2Cl2. Recrystallization from CH2Cl2/isopropanol provided
0.31 g (34%) of methyl indolylfulgide 9. E-form: 1H NMR (CDCl3,
400 MHz) d 7.40 (d, J = 7.9 Hz, 1H), 7.30 (d, J = 8.7 Hz, 1H), 7.24–
7.26 (m, 1H), 7.15 (td, J = 7.3, 1.1 Hz, 1H), 3.69 (s, 3H), 2.81 (s, 3H),
2.20 (s, 6H), 0.94 (s, 3H); 13C NMR (CDCl3, 100 MHz) d 164.1,
163.8, 153.1, 149.5, 137.1, 135.2, 125.0, 122.1, 121.6, 120.8, 119.6,
119.1, 116.7, 109.2, 29.9, 26.2, 24.7, 23.7, 12.2. C19H19NO3 MS
(APCI) m/z: 310.1451 [obtained M + H]+, 310.1438 [calculated M
+ H]+.
Synthesis of methyl carboxylic acid indolylfulgimide 4
Acetic anhydride (15 mL) was added to the amide diacid 11 (0.07 g,
0.18 mmol) in 15 mL of toluene at 0 ◦C. The reaction mixture
was allowed to stir at 0 ◦C for 2 h and then warmed to room
temperature. The reaction mixture was dissolved in 25 mL of
EtOAc and extracted with saturated NaHCO3 (3 ¥ 20 mL) and
H2O (2 ¥ 20 mL). The organic layer was dried over MgSO4,
filtered, and concentrated in vacuo. The residue was purified
by silica gel chromatography (70 : 30 : 1 EtOAc/hexanes/AcOH)
and provided an E/Z mixture (95 : 5) of methyl carboxylic acid
indolylfulgimide 4, which was difficult to separate. The E/Z
mixture was illuminated with 365 nm light in toluene until photo-
stationary state was reached, and then the C-form was purified by
silica gel chromatography (70 : 30 : 0.5 EtOAc/hexanes/AcOH).
Recrystallization from CH2Cl2–hexanes provided 21 mg (31%) of
C-form methyl carboxylic acid indolylfulgimide 4. The E-form
was prepared by illuminating the C-form in CDCl3 with visible
Synthesis of amide acid ester 10
1
N,N-Diisopropylethylamine (0.64 g, 4.97 mmol) was added drop-
wise to a mixture of the HCl salt of glycine methyl ester (0.23 g,
2.58 mmol) and methyl indolylfulgide 9 (0.22 g, 0.71 mmol) in
50 mL of acetonitrile at room temperature. The reaction mixture
light >515 nm. C-form: H NMR (CDCl3, 400 MHz) d 7.57 (d,
J = 7.6 Hz, 1H), 7.22 (td, J = 7.6, 1.0 Hz, 1H), 6.73 (td, J = 7.4,
1.1 Hz, 1H), 6.54 (d, J = 8.1 Hz, 1H), 4.28 (s, 2H), 2.89 (s, 3H), 2.41
(s, 3H), 1.76 (s, 3H), 1.28 (s, 3H), 1.18 (s, 3H); 13C NMR (CDCl3,
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The Royal Society of Chemistry and Owner Societies 2011 Photochem. Photobiol. Sci., 2011, 10, 1023–1029 | 1025
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