A facile synthesis of 1-substituted βcarboline derivatives via minisci-reaction

Article abstract of DOI:10.1080/00397911.2010.519092

A mild and efficient one-pot reaction for the synthesis of 1-substituted βcarboline derivatives via the Minisci reaction has been developed with good yields and selectivity. In addition, the mechanism of the 1-substituted βcarboline derivatives by means of the nucleophilic radical is described.

Full text of DOI:10.1080/00397911.2010.519092

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A Facile Synthesis of 1-Substituted
β-Carboline Derivatives via Minisci-
Reaction
a
a
a
a
Guowu Lin , Yue Wang , Qingfa Zhou , Weifang Tang , Jian
a
a b
Wang & Tao Lu
a
College of Basic Science, China Pharmaceutical University, Nanjing,
People's Republic of China
b
Key Laboratory of Drug Quality Control and Pharmacovigilance,
China Pharmaceutical University, Ministry of Education, Nanjing,
China
Available online: 08 Jun 2011
To cite this article: Guowu Lin, Yue Wang, Qingfa Zhou, Weifang Tang, Jian Wang & Tao Lu
(
2011): A Facile Synthesis of 1-Substituted β-Carboline Derivatives via Minisci-Reaction, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
1:23, 3541-3550
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1
Synthetic Communications , 41: 3541–3550, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.519092
A FACILE SYNTHESIS OF 1-SUBSTITUTED b-
CARBOLINE DERIVATIVES VIA MINISCI-REACTION
1
Guowu Lin, Yue Wang, Qingfa Zhou, Weifang Tang,
1
1
1
1
Jian Wang, and Tao Lu
1,2
1
College of Basic Science, China Pharmaceutical University, Nanjing,
People’s Republic of China
2
Key Laboratory of Drug Quality Control and Pharmacovigilance, China
Pharmaceutical University, Ministry of Education, Nanjing, China
GRAPHICAL ABSTRACT
Abstract A mild and efficient one-pot reaction for the synthesis of 1-substituted b-carboline
derivatives via the Minisci reaction has been developed with good yields and selectivity. In
addition, the mechanism of the 1-substituted b-carboline derivatives by means of the nucleo-
philic radical is described.
Keywords b-Carbolines; Minisci-reaction; nucleophilic radical; redox system
INTRODUCTION
Natural products have a profound impact upon both chemical biology and
drug discovery. One example is b-carbolines, which are found abundantly in plants
[
1–3]
and animals, many of which exhibit potent biological activities.
diverse biological activities of the naturally existing compounds, synthetically
In addition to the
[
4]
derived b-carbolines also exhibit significant bioactivities. The reported pharmaco-
logical effects of the natural and synthetic b-carbolines include antineoplastic (tubu-
[
4,5]
lin binding),
[
ligands),
anticonvulsive, hypnotic and anxiolytic (benzodiazepine receptor
[1]
6,7]
[3]
[8]
antiviral,
antimicrobial,
topoisomerase-II inhibitory,
and
[9]
cGMP-dependent inhibitory activities. Besides, the b-carboline scaffold is also
present in a variety of alkaloids isolated both from terrestrial plants
[11]
organisms with antiplasmodial activity.
[
10]
and marine
Received April 22, 2010.
Address correspondence to Tao Lu and Yue Wang, College of Basic Science, China Pharmaceutical
University, Nanjing 210009, China. E-mail: lut163@163.com; zwy_1115@126.com
3
541

3542
G. LIN ET AL.
Scheme 1. Mechanism of Minisci reaction.
Consequently, the synthesis of these alkaloids has attracted great interest in
recent decades. The majority of these alkaloids are substituted only at the 1-position,
and the classical approaches starting from tryptophan or tryptamine derivatives
(
Bischler–Napieralski, Pictet–Spengler) offer easy access to 1-aryl- and 1-alkyl-b-
[
12]
carbolines.
However, it seems difficult to introduce other electron-withdrawing
substituents (e.g., carbamoyl) directly in the 1-position of b-carboline derivatives
by these methods, while most of the active b-carbolines are substituted only at the
1
-position. Few synthetic approaches have been published on the synthesis of 1-
[
13,14]
substituted b-carbolines (electron-withdrawing substituents),
so a new and
effective way to synthesize the 1-substituted b-carbolines is urgently needed.
It has been reported that the Minisci reaction is a convenient strategy for sub-
stitution of protonated nitrogen heteroaromates (pyridines, pyrazines, quinolines,
quinoxalines, etc.) by nucleophilic radicals (e.g., carbamoyl radical) in a one-pot
reaction system. The substitution selectively occurs at the ortho- or para- positions
of the protonated ring nitrogen. Electron-withdrawing substituents strongly enhance
[
15]
the reactivity of the heterocyclic ring toward nucleophilic radicals. The mechanism
[
16]
of the Minisci reaction is generally described in Scheme 1.
ogous homolytic reactions of b-carboline derivatives have been reported so far.
However, few anal-
[
14]
RESULTS AND DISCUSSION
In this article, we described a one-step preparation of 1-substituted b-
carbolines (electron-withdrawing substituents) via regioselective homolytic reactions
[
including acylation, hydroxymethylation, formylation, carbamoylation, DMF
0
(
means of various nucleophilic radicals (including acetyl radical, hydroxymethyl rad-
N,N -dimethylformamide), and NMF (N-methylformamide)] of b-carbolines by
ical, formyl radical, carbamoyl radical, and N-methylcarbamoyl radical, and
0
N,N -dimethylcarbamoyl radical). These important substitution reactions have been
achieved by simple and commercially available starting materials, reagents, and
ꢀ
catalysts at 10–15 C according to the general Minisci reaction [Eq. 1 shown in
Scheme 2].

1
-SUBSTITUTED b-CARBOLINE DERIVATIVES
3543
Scheme 2. Mechanism for the synthesis of 1-substituted b-carboline derivatives.
Based on the classic Minisci reaction mechanism described previously and our
experimental results, the reaction mechanism of b-carboline derivatives with a var-
iety of nucleophilic radicals is proposed as shown in Scheme 2. The overall process
.
2
is summarized as follows. (i) Generation of the nucleophilic radical: Here R was
2
generated from different reagents (R -H) by FeSO and H O redox system
4
2
2
[
Eq. (1)]. (ii) Addition to the protonated b-carboline ring: In our experiment, b-
carboline ring was protonated by concentrated sulfuric acid [Eq. (2)]. (iii) Rearoma-
tization of the radical adducts: The mechanism illustrated by Eq. (3) has been
envisaged in the rearomatization step of the heteroaromatic substitution.
[
17]
Herein, two substrates (b-carbolines l and 3-ethoxycarbonyl-b-carboline 2)
were chosen to react with different reagents (methanol, formaldehyde, formamide,
acetaldehyde, DMF, and NMF) in the same reaction conditions (the FeSO and
4
ꢀ
H O redox system at 10–15 C) (see Scheme 3).
2
2
b-carbolines l were first selected as a starting material, because carbamoylation
should occur selectively at C-1 according to the regioselectivity described previously.
The reaction of protonated l with carbamoyl radical generated from formamide by
ꢀ
the FeSO and H O redox system at 10–15 C gave the expected 1-carbamoyl-b-
4
2
2
carboline 1a in 68% yield (entry 1 in Table 1). Under identical reaction conditions,
using acetaldehyde, methanol, DMF, NMF and formaldehyde instead of
Scheme 3. Synthesis of 1-substituted b-carboline derivatives using Minisci reaction.

3544
G. LIN ET AL.
Table 1. Reaction conditions and yields of 1-substituted b-carboline derivatives
1
Substrate (R )
2
Product (R )
ꢀ
Entry
Reagent
Time (min)
Yield (%)
Mp ( C)
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
HCONH
HCOCH
CH OH
HCON(CH
2
30
60
10
25
20
60
20
30
10
10
10
40
CONH
COCH
CH
CON(CH
2
(1a)
68
45
75
35
60
30
90
85
92
78
87
60
229–230
204–205
199–200
185–186
177–178
192–193
232–233
205–206
197–198
187–188
192–193
198–199
3
3
(1b)
3
2
OH (1c)
3
)
2
3
)
2
(1d)
(1e)
HCONHCH
HCHO
3
CONHCH
3
CHO (1f)
COOCH
COOCH
COOCH
COOCH
COOCH
2
2
2
2
2
CH
CH
CH
CH
CH
3
3
3
3
3
HCONH
HCOCH
CH OH
HCON(CH
2
CONH
COCH
CH
CON(CH
2
(2a)
3
3
(2b)
3
2
OH (2c)
1
1
1
0
1
2
3
)
2
3
)
2
(2d)
(2e)
HCONHCH
HCHO
3
CONHCH
3
CHO (2f)
COOCH CH
2
3
formamide, we obtained the corresponding products, including 1-acetyl-b-carboline
1
1
1
b in 45% yield (entry 2), 1-(hydroxymethyl)-b-carboline 1c in 75% yield (entry 3),
0
-(N,N -dimethylcarbamoyl)-b-carboline
1d
in
35%
yield
(entry
4),
-(N-methylcarbamoyl)-b-carboline 1e in 60% yield (entry 5), and 1-formyl-b-carbo-
line 1f in 30% yield (entry 6). The poor yields of 1b and 1f might be caused by the
poor solubility of b-carboline derivatives in aldehyde and formaldehyde, and the
poor yield of 1d might be attributed to stereospecific blockade of two methyl groups
in DMF.
Subsequently, we treated 3-ethoxycarbonyl-b-carboline (2) with differ-
ent reagents (including formamide, acetaldehyde, methanol, DMF, NMF and for-
ꢀ
maldehyde), FeSO4 and H O under standard conditions (10–15 C), giving
2
2
the expected products 1-carbamoyl-3-ethoxycarbonyl-b-carboline 2a in 90% yield
entry 7), 1-acetyl-3-ethoxycarbonyl-b-carboline 2b in 85% yield (entry 8),
(
1
-(hydroxymethyl)-3-ethoxycarbonyl-b-carboline 2c in 92% yield (entry 9), 1-
0
(
N,N -dimethylcarbamoyl)-3-ethoxycarbonyl-b-carboline 2d in78% yield (entry 10),
1
-(N-methylcarbamoyl)-3-ethoxycarbonyl-b-carboline 2e in 87% yield (entry 11),
and 1-formyl-3-ethoxycarbonyl-b-carboline 2f in 60% yield (entry 12), respectively.
We can see from Table 1 that the yields of 2a–2f are obviously greater than those
of 1a–1f, which can be explained by the activation of the electron-withdrawing sub-
stituent (the ester group) in the 3-position, for the electron-withdrawing substituent
should strongly activate the ring system for nucleophilic substitution. The greatest
yield of 2c shown in Table 1 is due to the electron-withdrawing group in the 3-
position of b-carboline and better solubility in methanol than in other solutions.
At the same time, we have obtained the colorless platelet crystals of 2a from
8
1
0% (v=v) methanol–water solution at room temperature. The structure consists of
-carbamoyl-3-ethoxycarbonyl-b-carboline 2a and one methanol molecule (Fig. 1).
In conclusion, we have developed a mild and efficient one-pot reaction for the
synthesis of 1-substituted b-carboline derivatives using the Minisci reaction at
ꢀ
1
carboline and various reagents (including methanol, formaldehyde, formamide, acet-
0–15 C. Under our optimized reaction conditions, using 3-ethoxycarbonyl-b-
aldehyde, DMF, and NMF) and cheap catalysts (the FeSO and H O redox system),
2
4
2
the reaction gave corresponding products 2a–2f in good yield and selectivity. This

1
-SUBSTITUTED b-CARBOLINE DERIVATIVES
3545
Figure 1. ORTEP drawing of X-ray crystal structure of compound 2a.
method offers a facile way to introduce various electron-withdrawing substituents to
b-carboline derivatives at the 1-positon, which broadened the scope of the Minisci
reaction. This type of reaction in preparation of 1-substituted b-carboline derivatives
[
18]
has been widely applied in our laboratory.
EXPERIMENTAL
All purchased starting materials and reagents were used without further puri-
fication unless noted. Reaction progress was monitored using analytical thin-layer
chromatography (TLC) on precoated Merck silica-gel Kiesegel 60 F254 plates,
and the spots were detected under ultraviolet (UV) light (254 nm). The flash chroma-
1
tography was conducted using silica gel (100–200) mesh. H NMR spectra were
recorded at 300 MHz on a Bruker ARX 300 spectrometer in dimethlsulfoxide
(DMSO-d ) solution. The chemical shifts were reported downfield in parts per mil-
6
lion (ppm d) relative to internal tetramethylsilane (TMS), and coupling constants
were reported in hertz (Hz). Mass spectra analysis was performed on a Quattro
microMS Micromass UK mass spectrometer and was recorded on an electrospray
ionization mass spectrometer as the value m=z. Melting points were determined with
a digital melting-point apparatus, and uncorrected values were reported. The x-ray
measurements were made on a Rigaku Raxis Rapid diffractometer with a graphite
˚
monochromatized Mo Ka radiation (k ¼ 0.71069 A) using x scan mode.
Typical Procedure
In a 150-ml, single-necked, round-bottomed flask equipped with a magnetic
stirrer, b-carboline derivative 1 or 2 (168 mg or 420 mg, 1.5 mmol), 50 mL formamide,

3546
G. LIN ET AL.
and 1 mL concentrated sulfuric acid were placed. The stirred mixture was cooled to
ꢀ
1
water) were added simultaneously over a period of 10 min, and stirring continued.
0–15 C. Then a saturated solution of FeSO ꢁ 7H O and H O (30% solution in
4
2
2
2
The addition of FeSO ꢁ 7H O and H O can be repeated until there is no starting
4
2
2
2
material left (TLC control). The reaction mixture was poured into water (150 mL),
followed by neutralization with saturated solution of sodium carbonate and extrac-
tion with ethyl acetate (3 ꢂ 100 mL). The combined organic layers were washed with
brine (1 ꢂ 100 mL) and dried with MgSO , and the solvent was removed under vac-
4
uum. The residue was purified by flash column chromatography. Other compounds
were synthesized similarly, and the spectroscopic data of 1a–1f and 2a–2f are as
follows.
Selected Data
[
14b]
1
-Carbamoyl-b-carboline (1a).
Yield: 144 mg (68%); white solid; mp
29–230 C; IR (KBr) 3404, 3269, 3169, 3057, 1697, 1626, 1597, 1487, 1425, 1361,
ꢀ
2
1
(
ꢃ1
1
317, 1288, 1259, 1224, 727, 542, 472 cm ; ESI-MS m=z 212.05 (M þ 1); H NMR
300 MHz, DMSO-d ) d11.64 (1H, s, indole), 8.33–8.40 (2H, m, ArH), 8.25 (2H, m,
6
ArH), 7.70 (2H, m, -CONH ), 7.56 (1H, m, ArH), 7.26 (1H, m, ArH).
2
[
14a]
1
-Acetyl-b-carboline (1b).
Yield: 95 mg (45%); pale yellow solid; mp
ꢃ1
ꢀ
2
04–205 C; IR (KBr) 3341, 2930, 1670, 1338, 1217, 1112, 735, 600, 497, 431 cm
1
;
ESI-MS m=z 211.05 (M þ 1); H NMR (300 MHz, DMSO-d ) d 12.30 (1H, s, indole),
6
9
(
-
.10 (1H, s, ArH), 8.45 (1H, d, J ¼ 7.9 Hz, ArH), 7.83 (1H, t, J ¼ 8.4 Hz, ArH), 7.64
1H, t, J ¼ 10.3 Hz, ArH), 7.53 (1H, m, ArH), 7.30 (1H, m, ArH), 2.80 (3H, s,
COCH ).
3
1
-(Hydroxymethyl)-b-carboline (1c). Yield: 149 mg (75%); white solid; mp
ꢀ
1
1
(
80–181 C; IR (KBr) 3315, 3126, 2902, 2843, 2665, 1626, 1573, 1489, 1429, 1319,
ꢃ1
1
205, 1024, 738, 671, 580, 545 cm ; ESI-MS m=z 199.00 (M þ 1); H NMR
300 MHz, DMSO-d ) d 11.35 (1H, s, indole), 8.25 (1H, m, ArH), 8.20 (1H, m,
6
ArH), 8.0 (1H, m, ArH), 7.65 (1H, m, ArH), 7.52 (1H, m, ArH), 7.20 (1H, m,
ArH), 5.48 (1H, t, J ¼ 5.6 Hz, -OH), 4.96 (2H, d, J ¼ 4.2 Hz, -CH -).
2
1
-(N,N’-Dimethylcarbamoyl)-b-carboline (1d). Yield: 84 mg (35%); white
ꢀ
solid; mp 169–170 C; IR (KBr) 3380, 2928, 1660, 1425, 1320, 1210, 735, 584, 492,
ꢃ1
1
4
(
40 cm ; ESI-MS m=z 240.10 (M þ 1); H NMR (300 MHz, DMSO-d ) d 12.1
6
1H, s, indole), 8.9 (1H, s, ArH), 8.53 (1H, d, J ¼ 7.6 Hz, ArH), 7.64 (1H, d,
J ¼ 8.4 Hz, ArH), 7.55 (1H, t, J ¼ 11.0 Hz, ArH), 7.33 (1H, t, J ¼ 9.0 Hz, ArH),
.20 (1H, m, ArH), 3.20 (6H, s, -NCH ꢂ 2).
7
3
1
-(N-Methylcarbamoyl)-b-carboline (1e). Yield: 135 mg (60%); white solid;
ꢀ
mp 157–158 C; IR (KBr) 3385, 3335, 3049, 1654, 1521, 1319, 1209, 734, 586, 491,
ꢃ1
1
4
(
35 cm ; ESI-MS m=z 226.05 (M þ 1); H NMR (300 MHz, DMSO-d ) d11.69
6
1H, s, indole), 8.88 (1H, d, J ¼ 8.7 Hz, ArH), 8.25–8.40 (3H, m, ArH), 7.78 (1H,
m, -CONH-), 7.56 (1H, m, ArH), 7.26 (1H, t, J ¼ 8.5 Hz, ArH), 2.5 (3H, d,
J ¼ 2.2 Hz, -NCH ).
3

1
-SUBSTITUTED b-CARBOLINE DERIVATIVES
3547
ꢀ
1
-Formyl-b-carboline (1f). Yield: 59 mg (30%); white solid; mp 162–163 C;
ꢃ1
IR (KBr) 3339, 2970, 1690, 1349, 1210, 1115, 730, 590, 495, 434 cm ; ESI-MS
1
m=z 197.05 (M þ 1); H NMR (300 MHz, DMSO-d ) d 12.33 (1H, s, indole), 10.11
6
(
1H, s, -CHO), 9.20 (1H, d, J ¼ 8.8 Hz, ArH), 8.20–8.40 (3H, m, ArH), 7.56 (1H,
m, ArH), 7.26 (1H, t, J ¼ 7.5 Hz, ArH).
1
-Carbamoyl-3-ethoxycarbonyl-b-carboline (2a). Yield: 255 mg (90%);
ꢀ
pale yellow solid; mp 189–190 C; IR (KBr) 3446, 3340, 3261, 3186, 2980, 2929,
ꢃ1
1
683, 1622, 1585, 1340, 1301, 1259, 1116, 1016, 746, 667, 621, 563, 503 cm ; ESI-MS
1
m=z 284.05 (M þ 1); H NMR (300 MHz, DMSO-d ) d12.07 (1H, s, indole), 9.08
6
(
1H, s, ArH), 8.44 (1H, d, J ¼ 7.9 Hz, ArH), 7.98 (2H, m, -CONH ), 7.86 (1H, d,
2
J ¼ 11.0 Hz, ArH), 7.62 (1H, m, ArH), 7.33 (1H, m, ArH), 4.43 (2H, q, -CH -),
2
1
.40 (3H, t, J ¼ 2.5 Hz, -CH ).
3
[14a]
1
-Acetyl-3-ethoxycarbonyl-b-carboline (2b).
Yield: 240 mg (85%); pale
yellow solid; IR (KBr) 3340, 3047, 2972, 1712, 1664, 1369, 1338, 1257, 1111, 1022,
ꢃ1
ꢀ
8
00, 738, 677, 607, 501, 430 cm ; mp 209–210 C; ESI-MS m=z 283.05 (M þ 1);
1
H NMR (300 MHz, DMSO-d ) d 12.29 (1H, s, indole), 9.16 (1H, s, ArH), 8.47
6
(
1H, d, J ¼ 8.0 Hz, ArH), 7.87 (1H, t, J ¼ 7.7 Hz, ArH), 7.70 (1H, m, ArH), 7.36
(1H, t, J ¼ 8.9 Hz, ArH), 4.45 (2H, q, -CH -), 2.83 (3H, s, -COCH ), 1.40 (3H, t,
2
3
J ¼ 3.0 Hz, -CH ).
3
1
-(Hydroxymethyl)-3-ethoxycarbonyl-b-carboline (2c). Yield: 248 mg
ꢀ
(
1
(
92%); white solid; mp 191–192 C; IR (KBr) 3225, 3095, 2982, 2935, 1703, 1498,
ꢃ1
458, 1338, 1249, 1145, 1105, 1026, 742, 671, 599 cm ; ESI-MS m=z 271.05
1
M þ 1); H NMR (300 MHz, DMSO-d ) d 11.80 (1H, s, indole), 8.83 (1H, s,
6
ArH), 8.36 (1H, d, J ¼ 8.1 Hz, ArH), 7.73 (1H, d, J ¼ 7.8 Hz, ArH), 7.56 (1H, t,
J ¼ 8.7 Hz, ArH), 7.28 (1H, t, J ¼ 9.9 Hz, ArH), 5.65 (1H, s, -OH), 4.99 (2H, s,
-
CH OH), 4.39 (2H, q, -CH -), 1.40 (3H, t, J ¼ 2.5 Hz, -CH ).
2
2
3
1
-(N,N’-Dimethylcarbamoyl)-3-ethoxycarbonyl-b-carboline (2d). Yield:
ꢀ
2
1
43 mg (78%); white solid; mp 187–188 C; IR (KBr) 3373, 3057, 2978, 2929,
ꢃ1
697,1600, 1491, 1454, 1398, 1348, 1255, 1116, 1057, 725, 636, 497, 424 cm
1
;
ESI-MS m=z 312.10 (M þ 1); H NMR (300 MHz, DMSO-d ) d 12.0 (1H, s, indole),
6
9
(
(
.0 (1H, s, ArH), 8.43 (1H, d, J ¼ 9.1 Hz, ArH), 7.61 (1H, d, J ¼ 8.0 Hz, ArH), 7.58
1H, m, ArH), 7.30 (1H, m, ArH), 4.41 (2H, q, -CH -), 3.18 (6H, s, -NCH ꢂ 2), 1.41
2
3
3H, t, J ¼ 2.5 Hz, -CH ).
3
1
-(N-Methylcarbamoyl)-3-ethoxycarbonyl-b-carboline
(2e). Yield:
59 mg (87%); white solid; mp 192–193 C; IR (KBr) 3377, 3313, 3076, 3051, 2972,
ꢀ
2
2
5
939, 1703, 1656, 1529, 1456, 1365, 1334, 1261, 1215, 1105, 1026, 729, 675, 613,
ꢃ1
1
34, 499, 434 cm ; ESI-MS m=z 298.10 (M þ 1); H NMR (300 MHz, DMSO-d )
6
d 12.12 (1H, s, indole), 9.0 (1H, s, ArH), 8.58 (1H, m, ArH), 8.43 (1H, m, ArH),
.86 (1H, m, -CONH-), 7.60 (1H, m, ArH), 7.32 (1H, m, ArH), 4.42 (2H, q,
CH -), 3.0 (3H, m, -NCH ), 1.40 (3H, t, J ¼ 2.6 Hz, -CH ).
7
-
2
3
3
1
-Formyl-3-ethoxycarbonyl-b-carboline (2f). Yield: 160 mg (60%); white
ꢀ
solid; mp 193–194 C; IR (KBr) 3363, 3047, 2970, 2931, 2835, 1726, 1685, 1583,
1
4
494, 1458, 1410, 1357, 1338, 1232, 1145, 1105, 1020, 956, 738, 667, 603, 505,
ꢃ1
1
34 cm ; ESI-MS m=z 269.15 (M þ 1); H NMR (300 MHz, DMSO-d ) d12.46
6

3548
G. LIN ET AL.
(
7
1H, s, indole), 10.3 (1H, s, -CHO), 9.2 (1H, s, ArH), 8.5 (1H, d, J ¼ 8.2 Hz, ArH),
.8 (1H, m, ArH), 7.65 (1H, m, ArH), d7.40 (1H, m, ArH), 4.45 (2H, q, -CH -), 1.40
2
(3H, t, J ¼ 2.5 Hz, -CH3).
SUPPLEMENTARY MATERIAL
CCDC 733671 contains the supplementary crystallographic data of 2a. These
data can be obtained free of charge from the Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
ACKNOWLEDGMENT
We are grateful to the National Natural Science Foundation of China (Project
0973609), the Fundamental Research Funds for the Central Universities (Program
3
No. 2J10004), and the Specialized Research Fund for the Doctoral Program of
Higher Education (Program No. 20100096110007) for financial support.
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-SUBSTITUTED b-CARBOLINE DERIVATIVES
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