1278 Journal of Natural Products, 2008, Vol. 71, No. 7
Notes
sively with hexanes, CHCl3, and EtOAc. The CHCl3 extract showed
strong activity against MCF-7, NCI-H460, and SF-268 cell lines.
Therefore the CHCl3 extract (14.7 g) was chromatographed on a Si
gel column by eluting with a gradient of CHCl3-MeOH (20:1) to
MeOH to yield seven fractions. Fraction 2 was chromatographed on
Si gel eluting with pure CHCl3 to yield 1 (30 mg) and 8 (10 mg).
Fraction 3 was chromatographed on Si gel using hexanes-acetone (4:
1) as eluent to obtain 6 (2 mg), 4 (12 mg), and 5 (2 mg). Fractions 4
and 5 were separately chromatographed on Si gel using CHCl3-MeOH
(50:1) as eluent to give 3 (3 mg) and 2 (4 mg), respectively. Owing to
the low solubility of 7 in organic solvents, it appeared in each fraction,
and the combined amount was 0.35 g.
6-Hydroxy-6-(2-oxodecyl)indolo[2,1-b]quinazolin-12-one (9, a
2-decanone adduct of tryptanthrin): colorless syrup; 66% yield; IR
(film) νmax 3418, 1655, 1600 cm-1; EIMS m/z 404 [M]+ (3), 263 (11),
249 (100), 220 (12), 192 (10), 130 (17), 102 (14); HRESIMS m/z
405.2176 [M + H]+ (calcd for C25H29N2O3, 405.2178); 1H NMR
(CDCl3, 300 MHz) δ 0.85 (3H, t, J ) 7.2 Hz), 1.25 (10H, m), 1.46
(2H, quintet, J ) 7.2 Hz), 2.37 (2H, t, J ) 7.2 Hz), 3.36 and 3.49
(each 1H, d, J ) 17.2 Hz), 5.06 (1H, br s), 7.16 (1H, t, J ) 8.0 Hz),
7.25 (1H, t, J ) 8.0 Hz), 7.48 (2H, m), 7.73 (2H, m), 8.24 (1H, d, J )
8.0 Hz), 8.34 (1H, d, J ) 8.0 Hz); 13C NMR (CDCl3, 75 MHz) δ 13.9,
22.4, 23.2, 27.3, 28.7, 28.9, 29.1, 31.6, 43.2, 50.5, 75.2, 116.2, 121.1,
122.8, 126.8 (2 x C), 126.9, 127.4, 129.8, 132.2, 134.1, 138.5, 147.0,
159.8, 159.9, 207.9.
Phaitanthrin A (1): white, amorphous powder; [R]D -25.1 (c 0.03,
CHCl3); UV (CHCl3) λmax (log ꢀ) 263 (3.18), 302 (2.92), 316 (3.03),
330 (3.01) nm; IR (KBr) νmax 3320, 1710, 1643, 1602 cm-1; EIMS
m/z 306 [M]+ (16), 262 (10), 249 (100), 220 (15), 192 (9), 149 (8),
130 (10), 57 (23); HREIMS m/z 306.1006 [M]+ (calcd for C18H14N2O3,
6-Hydroxy-6-(benzoylmethyl)indolo[2,1-b]quinazolin-12-one (10,
an acetophenone adduct of tryptanthrin): yellowish, amorphous
powder; 58% yield; IR (KBr) νmax 3435, 1644 cm-1; EIMS m/z 368
[M]+ (6), 249 (78), 220 (18), 192 (16), 130 (30), 120 (33), 105 (92),
77 (100); HRESIMS m/z 369.1237 [M + H]+ (calcd for C23H17N2O3,
369.1239); 1H NMR (CDCl3, 300 MHz) δ 3.95 and 4.16 (each 1H, d,
J ) 17.7 Hz), 4.70 (1H, br s), 7.23 (1H, t, J ) 7.8 Hz), 7.41 (3H, m),
7.52 (3H, m), 7.73 (2H, m), 7.87 (2H, m), 8.35 (1H, d, J ) 7.8 Hz),
8.52 (1H, d, J ) 7.8 Hz); 13C NMR (CDCl3, 75 MHz) δ 46.6, 76.7,
117.2, 122.1, 123.6, 126.9, 127.0, 127.4, 127.8, 128.1, 128.7, 130.5,
132.3, 133.9, 134.4, 136.2, 139.4, 147.2, 159.7 (2 × C), 197.7.
6-Hydroxy-6-(2-oxocyclopentyl)indolo[2,1-b]quinazolin-12-one (11
and 12, a cyclopentanone adduct of tryptanthrin): mixture of two
diastereomers in a 3:2 ratio; white, amorphous powder; 62% yield; IR
(KBr) νmax 3418, 1651 cm-1; EIMS m/z 332 [M]+ (6), 249 (100), 220
(19), 192 (25), 130 (49), 102 (59); HRESIMS m/z 333.1238 [M + H]+
(calcd for C20H17N2O3, 333.1239). Due to the instability of the product,
the mixture was quickly chromatographed on a Si gel column and eluted
with CH2Cl2-Et2O (20:1) to give some pure 11 and 12 for spectral
and cytotoxic analyses. Enantiomeric mixture of (6R,1′S)- and (6S,1′R)-
1
306.1004); H and 13C NMR data, Tables 1 and 2.
Phaitanthrin B (2): white, amorphous powder; [R]D -3.0 (c 0.21,
CHCl3); UV (CHCl3) λmax (log ꢀ) 259 (2.77), 334 (2.57) nm; IR (KBr)
νmax 3356, 1738, 1685, 1663, 1604 cm-1; EIMS m/z 322 [M]+ (20),
294 (13), 249 (100); HREIMS m/z 322.0951 [M]+ (calcd for
1
C18H14N2O4, 322.0954); H and 13C NMR data, Tables 1 and 2.
Phaitanthrin C (3): orange, amorphous powder; UV (CHCl3) λmax
(log ꢀ) 220 (4.11), 242 (4.08), 320 (3.43), 420 (3.38) nm; IR (KBr)
ν
max 3440, 1698, 1674, 1597 cm-1; EIMS m/z 264 [M]+ (11), 247 (15),
117 (100); HREIMS m/z 264.0533 [M]+ (calcd for C15H8N2O3,
264.0534); H and 13C NMR data, Tables 1 and 2.
1
Phaitanthrin D (4): yellow, amorphous powder; [R]D -6.9 (c 0.26,
CHCl3); UV (MeOH) λmax (log ꢀ) 204 (3.32), 236 (3.22), 284 (2.85),
402 (2.85) nm; IR (KBr) νmax 3349, 1780, 1633, 1614, 1592 cm-1
;
FABMS m/z 293 [M + H]+ (3), 167 (17), 149 (100); HRFABMS m/z
1
293.0927 [M + H]+ (calcd for C17H13N2O3, 293.0927); H and 13C
1
11: H NMR (CDCl3, 300 MHz) δ 1.21 (2H, m), 1.79 (2H, m), 2.40
NMR data, Tables 1 and 2.
(2H, m), 3.00 (1H, dd, J ) 9.9, 9.2 Hz), 5.30 (1H, br s), 7.37 (1H, t,
J ) 7.8 Hz), 7.50 (1H, t, J ) 7.8 Hz), 7.56 (2H, m), 7.75 (2H, m),
8.39 (1H, d, J ) 7.8 Hz), 8.52 (1H, d, J ) 7.8 Hz); 13C NMR (CDCl3,
75 MHz) δ 20.4, 25.3, 39.9, 53.1, 79.7, 117.1, 122.0, 123.9, 126.9,
127.1, 127.6, 128.0, 130.6, 130.9, 134.5, 139.3, 147.0, 159.3, 159.4,
Phaitanthrin E (5): white, amorphous powder; UV (CH3OH) λmax
(log ꢀ) 216 (4.59), 288 (3.64) nm; IR (KBr) νmax 3307, 1756, 1713,
1650, 1611 cm-1; FABMS m/z 293 [M + H]+ (7), 167 (18), 154 (100);
HRFABMS m/z 293.0923 [M + H]+ (calcd for C17H13N2O3, 293.0926);
1H and 13C NMR data, Tables 1 and 2.
1
220.9. Enantiomeric mixture of (6R,1′R)- and (6S,1′S)-12: H NMR
Methylisatoid (6): orange, amorphous powder; [R]D -8.0 (c 0.07,
CHCl3); UV (CHCl3) λmax (log ꢀ) 201 (3.11), 261 (3.18), 356 (2.99),
450 (3.02) nm; IR (KBr) νmax 3176, 1760, 1725, 1644, 1606, 1593
cm-1; EIMS m/z 308 [M]+ (3), 249 (100), 221 (55), 146 (19), 130
(23), 102 (14); HREIMS m/z 308.0796 [M]+ (calcd for C17H12N2O4,
(CDCl3, 300 MHz) δ 1.02 (1H, m), 1.80 (3H, m), 2.14 (1H, m), 2.52
(1H, dd, J ) 18.5, 6.6 Hz), 3.31 (1H, dd, J ) 11.6, 8.1 Hz), 5.79 (1H,
br s), 7.31 (1H, t, J ) 8.0 Hz), 7.36 (1H, d, J ) 8.0 Hz), 7.52 (1H, t,
J ) 8.0 Hz), 7.57 (1H, t, J ) 8.0 Hz), 7.80 (1H, t, J ) 8.0 Hz), 7.87
(1H, d, J ) 8.0 Hz), 8.40 (1H, d, J ) 8.0 Hz), 8.58 (1H, d, J ) 8.0
Hz); 13C NMR (CDCl3, 75 MHz) δ 20.2, 25.2, 39.7, 54.9, 79.4, 117.4,
122.0, 123.7, 127.0, 127.1, 127.8, 128.1, 130.7, 131.0, 134.6, 139.6,
147.2, 157.9, 159.5, 222.6.
1
308.0797); H and 13C NMR data, Tables 1 and 2.
Tryptanthrin (7): yellow needles (CHCl3); mp 260-261 °C (lit.18
260-261 °C); UV (CHCl3) λmax (log ꢀ) 253 (3.69), 313 (0.49), 335
(0.46), 399 (0.42) nm; IR (KBr) νmax 1725, 1684 cm-1; EIMS m/z 248
[M]+ (100), 220 (20), 192 (25); HREIMS m/z 248.0587 [M]+ (calcd
X-ray Crystallographic Data of 11. Colorless single crystals of
11 suitable for X-ray diffraction study were grown by recrystallization
from CH2Cl2-MeOH. Data were obtained on a Siemens Smart CCD
1000 diffractometer with graphite-monochromated Mo KR radiation,
operating at 50 kV and 35 mA at 296 K, over a 2θ range of
5.06-56.62°. Data were processed on a Pentium III PC using the Bruker
AXS SHELXTL, NT software package. Neutral atom scattering factors
were taken from Cromer and Waber. 6-Hydroxy-6-(2-oxocyclopentyl)-
indolo[2,1-b]quinazolin-12-one (11): C20H16N2O3, Mr ) 332.35; crystal
size 0.30 × 0.25 × 0.25 mm3; monoclinic, space group P2(1)/n; unit
cell dimensions: a ) 12.1325(19) Å, b ) 10.4626(17) Å, c ) 12.994(2)
Å, R ) 90°, ꢀ ) 103.455(2)°, γ ) 90°; volume: 1604.2(4) Å3; Z ) 4;
Dc ) 1.376 Mg/m3. The structures were refined by full-matrix least-
squares on F2 using SHELEXL-97 (Sheldrick, 1997). Final discrepancy
indices of R1 ) 0.0490, wR2 ) 0.1434 and GOOF ) 1.091 for observed
data with I > 2σ(I). Crystallographic data for the structure 11 (CCDC-
675761) reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre. Copies of the data can be obtained, free
ing.html (or from the CCDC, 12 Union Road, Cambridge CB2 1EZ,
6-Hydroxy-6-(3-oxopentan-2-yl)indolo[2,1-b]quinazolin-12-one (13,
a 3-pentanone adduct of tryptanthrin): mixture of two diastereomers
in a 2:1 ratio; white, amorphous powder; 68% yield; IR (KBr) νmax
1
for C15H8N2O2, 248.0586); H and 13C NMR data, Tables 1 and 2.
Candidine (8): purple needles (CHCl3);mp 267-268 °C (lit.19
269-270 °C); UV (CHCl3) λmax (log ꢀ) 250 (4.16), 284 (4.00), 574
(3.88) nm; IR (KBr) νmax 3225, 1688, 1675, 1627, 1606 cm-1; EIMS
m/z 363 [M]+ (100), 335 (43), 259 (24); HREIMS m/z 363.1006 [M]+
(calcd for C23H13N3O2, 363.1008); 1H NMR (CDCl3, 300 MHz) δ 7.06
(1H, t, J ) 7.4 Hz, H-5′), 7.10 (1H, d, J ) 7.4 Hz, H-7′), 7.41 (1H, t,
J ) 7.6 Hz, H-8), 7.49 (1H, t, J ) 7.6 Hz, H-9), 7.53 (1H, t, J ) 7.9
Hz, H-2), 7.55 (1H, t, J ) 7.4 Hz, H-6′), 7.77 (1H, d, J ) 7.4 Hz,
H-4′), 7.82 (1H, m, H-3 and -4), 8.44 (1H, d, J ) 7.9 Hz, H-1), 8.68
(1H, d, J ) 7.6 Hz, H-10), 9.24 (1H, d, J ) 7.6 Hz, H-7), 11.73 (1H,
br s, H-1′); 13C NMR (CDCl3, 75 MHz) δ 107.7 (C-6), 112.2 (C-7′),
116.5 (C-10), 120.4 (C-9′), 120.7 (C-12a), 122.0 (C-5′), 124.0 (C-6a),
125.4 (C-4′ and -7), 126.5 (C-8), 127.2 (C-1, -2, and -4), 129.6
(C-9), 134.3 (C-3), 136.7 (C-6′), 137.7 (C-10a), 138.5 (C-5a), 146.8
(C-4a), 150.8 (C-8′), 154.4 (C-2′), 159.1 (C-12), 187.4 (C-3′).
Synthesis of Ketone Adduct of Tryptanthrin. The tryptanthrin
was prepared according to Moskovkina’s method.18 Then, 5 mL of
ketone (acetone, 2-decanone, acetophenone, cyclopentanone, or
3-pentanone) was added to tryptanthrin (1 mmol). Diethylamine (3
mmol) was added to the mixture. The resulting suspension was
stirred at room temperature for 1 day.20 The clear solution was
directly chromatographed on a Si gel column by eluting with CH2Cl2
to give pure ketone adducts 9-13.
3402, 1661, 1602 cm-1
; EIMS m/z 334 [M]+ (2), 249 (100), 220 (12),
192 (13), 130 (30), 102 (27); HRESIMS m/z 335.1397 [M + H]+ (calcd