4738
J. Tummatorn et al. / Tetrahedron 68 (2012) 4732e4739
(neat): nmax 3376, 2927, 1506, 1246, 749 cmꢁ1
;
1H NMR (300 MHz,
138.8, 129.6, 128.1, 125.8, 125.6, 122.1, 121.9, 120.7, 120.2, 117.1, 114.3,
CDCl3)
d
7.25 (d, 1H, J¼7.2 Hz), 7.09 (t, 1H, J¼7.8 Hz), 6.93 (d, 1H,
111.9; TOF-HRMS calcd for C15H11N2 (MþH)þ 219.0917, found
J¼2.7 Hz), 6.83e6.78 (m, 2H), 6.64 (dd, 1H, J¼8.4, 2.7 Hz), 6.55 (d,
1H, J¼8.7 Hz), 5.26e5.20 (m, 1H), 4.60 (d, 1H, J¼9.0 Hz), 3.79 (s, 3H),
3.75 (br s, 1H), 3.46 (dd, 1H, J¼12.0, 4.5 Hz), 3.26 (dd, 1H, J¼12.0,
219.0910.
4.3.3. Isocryptolepine (10). To solution of compound 9 (38.7 mg,
0.18 mmol) in CH3CN (5 mL) was added Me2SO4 (67.0 mg,
0.53 mmol). The reaction mixture was stirred at reflux for 3 h and
was cooled to room temperature. The reaction mixture was then
quenched with satd aq NaHCO3 (10 mL) and allowed to stir over-
night. The resulting mixture was added with H2O (5 mL), extracted
with EtOAc (3ꢂ15 mL). The combined extracts were washed with
brine, dried over Na2SO4, filtered, and concentrated at reduced
pressure. The residue was purified on silica gel using 10% MeOH in
DCM to give compound 10 (32.2 mg, 78%) as a yellow solid; Rf (5%
MeOH/CH2Cl2) 0.24; mp 190e191 ꢀC; IR (neat): nmax 3050, 1637,
3.3 Hz); 13C NMR (75 MHz, CDCl3)
d 159.2, 153.4, 139.3, 130.2, 128.4,
125.0, 124.8, 120.7, 116.8, 114.3, 112.9, 109.6, 81.6, 55.8, 45.7, 42.7;
TOF-HRMS calcd for C16H16NO2 (MþH)þ 254.1176, found 254.1180.
4.2.18. 5,6,6a,11b-Tetrahydrobenzo[h]benzofuro[2,3-c]quinoline
(6s). Yield 141 mg (95%, viscous pale yellow oil); Rf (20% EtOAc/
hexane) 0.47; IR (neat): 3414, 3052, 2917, 1521, 1477, 1232,
749 cmꢁ1 1H NMR (300 MHz, CDCl3)
; d 7.76e7.67 (m, 2H), 7.47 (d,
1H, J¼8.4 Hz), 7.43e7.31 (m, 4H), 7.08 (t, 1H, J¼7.7 Hz), 6.82e6.77
(m, 2H), 5.33e5.27 (m, 1H), 4.74 (d, 1H, J¼8.8 Hz), 4.46 (br s, 1H),
3.65 (dd, 1H, J¼12.4, 4.7 Hz), 3.45 (dd, 1H, J¼12.4, 3.3 Hz); 13C NMR
1597, 1351 cmꢁ1; 1H NMR (300 MHz, DMSO-d6)
d 9.46 (s, 1H), 8.76
(75 MHz, CDCl3)
d
159.0, 140.0, 132.9, 131.1,128.5, 128.4, 127.0, 125.6,
(d,1H, J¼8.0 Hz), 8.12 (d,1H, J¼7.7 Hz), 8.07 (d,1H, J¼8.6 Hz), 7.86 (t,
1H, J¼7.2 Hz), 7.79 (d, 1H, J¼8.1 Hz), 7.74 (t, 1H, J¼7.7 Hz), 7.47 (t, 1H,
J¼7.4 Hz), 7.29 (t, 1H, J¼7.4 Hz), 4.27 (s, 3H); 13C NMR (75 MHz,
125.2, 124.8, 123.5, 120.7, 119.6, 119.3, 117.5, 109.9, 81.3, 44.6, 42.8;
TOF-HRMS calcd for C19H16NO (MþH)þ 274.1226, found 274.1228.
DMSO-d6)
d 151.2, 150.5, 139.4, 135.5, 130.0, 126.0, 125.9, 124.7,
4.2.19. 6-Methyl-5,6,6a,11b-tetrahydrobenzofuro[2,3-c]quinoline
(6t). Yield 98.4 mg (58%, colorless crystal); Rf (20% EtOAc/hexane)
0.45; mp 174e175 ꢀC; IR (neat): nmax 2962, 1618, 1220, 1030,
124.0, 120.6, 119.9, 119.8, 117.9, 117.2, 115.5, 42.6; TOF-HRMS calcd
for C16H13N2 (MþH)þ 233.1073, found 233.1074.
748 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d
7.32 (d,1H, J¼7.5 Hz), 7.21 (d,
Acknowledgements
1H, J¼1.2 Hz), 7.06 (t, 1H, J¼7.8 Hz), 6.99 (t, 1H, J¼7.5 Hz), 6.82e6.75
(m, 3H), 6.56 (d,1H, J¼7.8 Hz), 5.08 (dd,1H, J¼9.0,1.2 Hz), 4.63 (d,1H,
J¼9.0 Hz), 3.49 (br s,1H), 3.42 (q,1H, J¼6.6 Hz),1.50 (d, 3H, J¼6.6 Hz);
This research work was supported in part by grants from Center
of Excellence on Environmental Health and Toxicology, Science &
Technology Postgraduate Education and Research Development
Office (PERDO), Ministry of Education, Chulabhorn Research In-
stitute, and Thailand Research Fund (TRF).
13C NMR (75 MHz, CDCl3)
d 159.5, 145.8, 130.7, 128.4, 128.1, 127.1,
124.7, 124.5, 120.6, 119.8, 115.7, 109.5, 86.0, 50.8, 43.3, 17.6; TOF-
HRMS calcd for C16H16NO (MþH)þ 238.1226, found 238.1224.
4.3. Synthesis of isocryptolepine (10)
Supplementary data
4.3.1. 11-(Phenylsulfonyl)-11H-indolo[3,2-c]quinoline (8). To a solu-
tion of 6o (264 mg, 0.728 mmol) in DCM (6 mL) was added 2,3-
Supplementary data related to this article can be found online at
InChiKeys of the most important compounds described in this article.
dichloro-5,6-dicyano-1,4-benzoquinone
(DDQ)
(414
mg,
1.82 mmol) at room temperature. The reaction mixture was stirred
overnight and then diluted with water. The organic mixture was
successively washed with 1.0 M aq NaOH until the solution turned
pale yellow. The combined organic mixture was further washed
with water and dried over Na2SO4, filtered, concentrated under
reduced pressure, and purified on silica gel using 30% EtOAc/hexane
to yield 246 mg (94%) of compound 8 as a pale yellow solid; Rf (20%
EtOAc/hexane) 0.13; mp 135e136 ꢀC; IR (neat): nmax 3066, 2920,
References and notes
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ꢀ
1375, 1179, 919, 750 cmꢁ1; 1H NMR (300 MHz, CDCl3)
d 9.31 (s, 1H),
9.07 (d, 1H, J¼8.4 Hz), 8.39 (d, 1H, J¼8.4 Hz), 8.23 (d, 1H, J¼8.1 Hz),
7.88 (d, 1H, J¼7.8 Hz), 7.77 (t, 1H, J¼7.2 Hz), 7.70 (t, 1H, J¼8.1 Hz),
7.52 (t, 1H, J¼7.8 Hz), 7.42 (t, 1H, J¼7.5 Hz), 7.29 (t, 1H, J¼7.2 Hz), 7.15
(d, 2H, J¼8.1 Hz), 7.05 (t, 2H, J¼7.5 Hz); 13C NMR (75 MHz, CDCl3)
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~
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9. Marcoux, D.; Bindschadler, P.; Speed, A. W. H.; Chiu, A.; Pero, J. E.; Borg, G. A.;
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148.3, 143.3, 142.0, 140.9, 135.3, 133.8, 129.9, 128.9, 128.4, 127.5,
Evans, D. A. Org. Lett. 2011, 13, 3758e3761.
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HRMS calcd for C21H15N2O2S (MþH)þ 359.0849, found 359.0851.
ꢀ
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4.3.2. 11H-Indolo[3,2-c]quinoline (9). Compound
8
(874 mg,
201e205.
2.44 mmol) was added to 2 M aq NaOH solution in MeOH (30 mL).
The reaction mixture was stirred at reflux for 5 h and was neu-
tralized with 2 M aq HCl (30 mL) and extracted with EtOAc
(3ꢂ30 mL). The combined extracts were washed with H2O and
brine, dried over Na2SO4, filtered, and concentrated at reduced
pressure. The residue was purified on silica gel using 50e100 %
EtOAc/hexane to give compound 9 (504 mg, 95%) as a white solid; Rf
(100% EtOAc) 0.56; mp 332e333 ꢀC; IR (neat): nmax 3047, 2925,
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1567, 1339, 1237, 733 cmꢁ1 1H NMR (300 MHz, DMSO-d6)
; d 12.75
(br s, 1H), 9.60 (s, 1H), 8.52 (d, 1H, J¼7.8 Hz), 8.32 (d, 1H, J¼7.8 Hz),
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8.14 (d, 1H, J¼8.1 Hz), 7.77e7.67 (m, 3H), 7.51 (t, 1H, J¼7.5 Hz), 7.36
(t, 1H, J¼7.9 Hz); 13C NMR (75 MHz, DMSO-d6)
d
145.5, 144.9, 139.8,