CoCl2-promoted TEMPO oxidative homocoupling of indoles: Access to tryptanthrin derivatives

Article abstract of DOI:10.1039/c8ob01216d

A novel TEMPO/CoCl₂-promoted aerobic oxidation of indoles was developed. The reaction provided one-step access to tryptanthrin derivatives in moderate to good yields and excellent regioselectivity via a cascade process. The reactions could be carried out under mild reaction conditions with varying functional group tolerance, especially halogen functional groups. Mechanistic studies disclosed that the oxygen atom in the desired product originated from molecular dioxygen.

Full text of DOI:10.1039/c8ob01216d

View Article Online
View Journal
Organic &
Biomol ec ular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: L. Liu, H. Liao, X.
Peng, D. Hu, X. Xu, P. Huang and Q. Liu, Org. Biomol. Chem., 2018, DOI: 10.1039/C8OB01216D.
Volume 14 Number
1
7
January 2016 Pages 1–372
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Page 1 of 12
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB01216D
CoCl -Promoted TEMPO Oxidative Homocoupling of Indoles:
2
Access to Tryptanthrin Derivatives
a
b,†
a
b
a
b
Huiwu Liao, Xiangjun Peng, Dan Hu, Xianyun Xu, Panpan Huang, Qian Liu,*
a
Liangxian Liu*
a
Department of Chemistry and Chemical Engineering, Gannan Normal University, Ganzhou,
Jiangxi 341000, P. R. China
b
School of Pharmaceutical Science, Gannan Medical University, Ganzhou, Jiangxi 341000, P. R.
China
E-mail: liuliangxian1962@163.com
Abstract: A novel TEMPO/CoCl -promoted aerobic oxidation of indoles was developed. The
2
reaction provided one-step access to tryptanthrin derivatives in moderate to good yields and
excellent regioselectivity via a cascade process. The reactions could be carried out under mild
reaction conditions with varying functional group tolerance, especially halogen functional groups.
Mechanistic studies disclosed that the oxygen atom in the desired product was originated from
molecular dioxygen.
Keywords: TEMPO; Tryptanthrin; Indole; Carbonylation
Introduction
Tryptanthrin, a naturally occurring indolo[2,1-b]quinazoline alkaloid, was formed and isolated
from a number of plants such as Isatis, Calanthe, Wrightia, Couroupota, and Strobilanthes cusia
1
(
Acanthaceae). It shows remarkable cytotoxicity against various cancer cell lines, including
human breast carcinoma (MCF-7), lung carcinoma (NCI-H460), and central nervous system
2
3
carcinoma (SF-268). It also shows potent antimicrobial, antifungal, and antileishmanial activity.
4
In recent years, tryptanthrin derivatives have been reported to act as potent antitubercular agents.
For example, Phaitanthrin A 2, isolated from Phaius mishmensis (Orchidaceae), showed moderate
2
,5
cytotoxicity against MCF-7, NCI-H460, and SF-268 cell lines. Owing to their importance and
6
-9
potential utility, significant progress has been made in the synthesis of tryptanthrin. It should be
noted that the most common synthesis route to tryptanthrin involves the condensation of istin and
a nitrogen-containing compound (Scheme 1). However, many of these methods involve
step-by-step synthetic strategies. Therefore, the development of a concise and one-step strategy for
the synthesis of tryptanthrin derivatives using different substrates is highly desirable to increase
9
c
the diversity of tryptanthrin derivatives. More recently, a ZnO-NP catalyzed direct indolation of
in situ generated tryptanthrin via C–H functionalization and C–C bond formation has been
9d
developed.
Figure. 1 Bioactive alkaloids containing the tryptanthrin scaffold.
Oxidation reactions are among the most important classes of reactions in organic synthesis, and

Organic & Biomolecular Chemistry
Page 2 of 12
View Article Online
DOI: 10.1039/C8OB01216D
10
their synthetic scope and utility have advanced significantly over the past few decades. Most
efforts have been directed to the development of transition metal-based catalysts. In contrast,
much less attention has been paid to the development of non-metallic oxidation systems, largely
11
ignoring their inherent advantages. The radical 2,2,6,6-tetramethylpiperidine 1-oxyl radical
TEMPO) and its derivatives are well-established catalysts for oxidation processes, and now used
(
extensively in industrial applications and organic synthesis as a safe, mild, and economical
alternative to heavy metal reagents as highly selective oxidation catalysts for the production of
12
pharmaceuticals, fragrances, flavors, agrochemicals, and a variety of other specialty chemicals.
As part of a continuing program, our group developed a range of transformations that enable the
1
3
direct functionalization of indole derivatives via TEMPO catalysis. Based on our previous
13
studies, we envisioned that the direct transformation of indoles to tryptanthrin derivatives could
be achieved by employing appropriate transition-metal catalyst combined with TEMPO. Herein,
we report a new strategy for the synthesis of tryptanthrin derivatives from indoles using
2
TEMPO/CoCl under aerobic conditions. Very few methods report the self-condensation of indole
to generate tryptanthrin. To the best of our knowledge, this work represents the first example of
one-step synthesis of tryptanthrin derivatives via direct C-H transformation.
Scheme 1. Previous approaches.
Results and discussion
With the hypothesis mentioned above, our optimization studies began with indole 5a as model
substrate and TEMPO as oxidant in DMF. Representative results are shown in Table 1. Initially, a
low yield of the desired product 6a was obtained when DABCO was used as an essential additive
and copper salts or CoSO
as FeCl , FeSO , Ag CO
4
as catalysts (Table 1, entries 6-8). Other transition metal catalysts, such
3
4
2
3
, NiSO , and ZnSO , showed no reactivities (Table 1, entries 1-5). The
4
4
structure of 6a was confirmed by X-ray crystallography (see Supporting Information). Among the
cobalt sources used, CoCl exhibited the highest catalytic reactivity (Table 1, entries 8-11). It was
2
also found that the use of TEMPO as an oxidant is critical to the reaction. In the absence of
TEMPO, no conversion was observed under these conditions and indole was recovered mostly,
whereas, at 45 mol % of TEMPO, the desired product was obtained in 65% yield, and at lower or
higher loading, the yield decreased (Table 1, entries 13-16). The solvent was also found to have a
dramatic impact on the efficiency of the reaction. DMF was found to be the best choice.
3
Interestingly, THF, benzene, CH CN and pyridine proved to be inefficient for the formation of 6a
(Table 1, entries 18-21). The influence of temperature was also studied. When temperature was

Page 3 of 12
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB01216D
increased to 70 °C, the yield increased from 65% to 78%; however, lowering the temperature to
0 °C only dramatically reduced the yields of desired product 6a to 29% (Table 1, entries 23-26).
On the basis of our screening experiments, the best results were obtained using a treatment of 60
mol % CoCl (see Supporting Information), 0.45 equiv of TEMPO, and 0.5 equiv of DABCO in
4
2
DMF at 70 °C for 48 h, which afforded the desired product 6a in high yield (78%, entry 25).
a
Table 1. Selected optimization of the reaction conditions
O
N
conditions
N
N
H
HO
5a
NH
6a
a
Conditions: 5a (0.3 mmol), catalyst (0.06 mmol), DABCO (0.15 mmol), and solvent (1 mL), 48
b
h, under open air. Isolated yield.
With the optimal reaction conditions available, the protocol was extended to different indoles. The
results are shown in Table 2. In general, the reaction proceeded smoothly to give the desired
products in generally good yields (53 to 87%) and can tolerate a variety of functional groups at the
5
3 3
, 6, and 7 positions of indoles, such as F, Cl, Br, I, CH , CH O, and CN. The substituent effect on
the indole ring was then investigated. The results have shown that electronegativities of
substituents played a major role in governing the reactivity of the substrates. Electron-donating
substitutents showed better results than electron-withdrawing substitutents in this transformation.
3 3
For example, 5-substituted indole derivatives with electron-donating substituents (CH and OCH )
afforded the desired 6e and 6f in 83% and 87% yields, respectively (Table 2, entries 5 and 6).
While 5-substituted indole derivatives with electron-withdrawing substituents (F, Br, I) provided
the desired products 6b-6d in yields ranging from 70% to 75% (Table 2, entries 2-4). It is worth
noting that substrate with a strong electron-withdrawing substituent at C5-position, such as CN,

Organic & Biomolecular Chemistry
Page 4 of 12
View Article Online
DOI: 10.1039/C8OB01216D
gave 6g in 53% yield (Table 2, entry 7). This is particularly important, since substrates with a
strong electron-withdrawing group disfavored the homocoupling of indoles and there were few
14
examples reported. Furthermore, we were pleased to find that indoles bearing an halogen atom
including fluoro, chloro, bromo, and iodo at the C5-, C6- or C7-position worked well and desired
products were obtained in good yields. Tolerance to the halogen functional groups is especially
noteworthy since they are useful for subsequent cross-coupling reactions.
a
Table 2. Substrate scope
Entry
R
H
5-F
5-Br
5-I
5-CH3
5-OCH3
5-CN
6-F
6-Cl
7-Cl
7-Br
Product
6a
Yield [%]b
1
2
3
4
5
6
7
8
9
78
70
72
75
83
87
53
64
69
73
72
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
1
1
0
1
a
Conditions: 5 (0.3 mmol), CoCl
2
(0.06 mmol), TEMPO (0.135 mmol), DABCO (0.15 mmol),
b
and DMF (1 mL), 48 h, under open air. Isolated yield.
Next, the synthetic method was extended to 2-substituted indole derivatives, such as
2
-methyl-1H-indole 7a, 5-chloro2-methyl-1H-indole 7b, and 2,5-dimethyl-1H-indole 7c,
providing straightforward pathway to synthesize unexpected
,2''-dimethyl-3'-oxo-(3,2':2',3''-terindoline)-1'-carbaldehydes 8. As shown in Scheme 2, when 7c
a
2
was subjected to the standard reaction conditions, 8c could be easily obtained in 81% yield. These
results indicate that the CH at the C2-position of indoles can be cut off under the optimized
3
conditions. The structure of 8a was confirmed by X-ray single-crystal diffraction, and the
molecular structure is given in the Supporting Information. 3-Oxindole derivatives are known to
1
5
possess a variety of biological activities. For example, the leaves and root of Isatis indigotica
Fort., named “Da-Qing-Ye” and “Ban-Lan-Gen” respectively in Chinese, have been used in
16
traditional Chinese medicine for the treatment of viral diseases for hundreds of years in China.
In addition, we found that 1 was formed in 45% yield when 2-methyl indole 7a was reacted in
dioxygen (1 atm, balloon) under standard reaction conditions and only trace amount of the product
3
8a was obtained (Scheme 2). These results indicate that the CH at the C2-position of indoles can
be cut off under the optimized conditions.

Page 5 of 12
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB01216D
Scheme 2. Reaction of 2-methyl-1H-indoles.
We further performed several control experiments under the standard conditions in order to probe
the reaction mechanism. First, indole was reacted in dioxygen (1 atm, balloon) instead of air under
standard reaction conditions. Pleasingly, the desired product 6a was formed in 76% yield for 24 h.
However, only trace amount of the product was obtained under an argon atmosphere, even a long
reaction time. These results indicated that O
transformation (Scheme 3).
2
is essential for the TEMPO/Co-promoted
Scheme 3. Control experiments.
Second, it was found that isatin 9 reacted with 5-methoxy indole 5e under standard reaction
conditions to give the desired product 10 in 56% yield (Scheme 4). This result showed that 9 is the
3
intermediate of homocoupling. Under the optimized conditions, N-CH indole 11 was chosen as a
substrate instead of indole. To our surprise, no conversion was observed, indicating that the N-H
of indole is necessary in the reaction.
Scheme 4. Controlled Experiments with isatin, 5e and 11.
18
Furthermore, we designed two O labeled experiments and the reaction of 5a in the presence of
18
18
18
2
O (1 atm) generated the O labeled product O-6a in 63% yield (Scheme 5). With the addition

Organic & Biomolecular Chemistry
Page 6 of 12
View Article Online
DOI: 10.1039/C8OB01216D
18
2
16
of 3 equiv of H
O under standard reaction conditions, 98% of the product contained O.
Therefore, we have reason to believe that the oxygen atom in the desired product was originated
from molecular dioxygen.
18
Scheme 5. O Labeled experiments.
7
On the basis of these experimental results and previous reports, a plausible reaction pathway for
this transformation is illustrated in Scheme 6. Initially, 5a was aerobically oxidized using TEMPO
17
to indolin-3-one 12, which could further oxidize to isatin 9. Then, 9 underwent hydrolysis to
produce intermediate 13, which followed by TEMPO/CoCl -promoted decarboxylative coupling
2
with 12 to afford intermediate 14. 14 was sequentially oxidized to imminium 15. The amine
nitrogen atom attacked the carbon-nitrogen double bond followed by cyclization and
aromatization to produce the tryptanthrin 1. Finally, the nucleophilic attack of 5a to 1 produced
the final product 6a.
Scheme 6. Proposed reaction pathway for the formation of 6a.
Conclusions
In summary, we developed a new one-step strategy for the synthesis of tryptanthrin derivatives
from indoles. The reactions could be carried out under mild reaction conditions with varying
functional group tolerance, especially halogen functional groups. Moreover, it has several
advantages: (1) the operationally simple make it potentially useful, (2) it is highly regioselective
(
C3-selective carbonylation of indoles), (3) the high halogen compatibility of the process, (4) this
cascade process proceeds without exclusion of moisture or air from the reaction mixture and
allows the isolation of the desired 6-hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-
ones in moderate to excellent yields. This cascade will be useful for a diversity-oriented approach
to explore the biological activities of these tryptanthrin derivatives.
Experimental Section

Page 7 of 12
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB01216D
General
1
13
H and C NMR spectra were recorded on a Bruker spectrometers at 400 and 100 MHz,
respectively. Mass spectra were recorded with Bruker Dalton Esquire 3000 plus LC-MS apparatus.
Elemental analysis were carried out on a Perkin-Elmer 240B instrument. Silica gel (300-400 mesh)
was used for flash column chromatography, eluting (unless otherwise stated) with an ethyl
acetate/petroleum ether (PE) (60-90 °C) mixture.
General Procedure for the Preparation of 6.
To a solution of indole (0.3 mmol), CoCl (0.06 mmol), and TEMPO (0.135 mmol) in DMF (1 mL)
2
o
was added DABCO (0.15 mmol) under an air atmosphere and the mixture was stirred at 70 C for
48 h. The reaction mixture was concentrated under reduced pressure. The residue was purified by
flash chromatography on silica gel (eluent: EtOAc/PE = 1:1) to yield the corresponding product 6.
1
Indolo[2,1-b]quinazoline-6,12-dione (tryptanthrin) (1). H NMR (400 MHz, DMSO-d
6
): δ 8.49 (d,
J = 7.9 Hz, 1H, Ar-H), 8.33 (d, J = 7.9 Hz, 1H, Ar-H), 7.95 (d, J = 3.7 Hz, 2H, Ar-H), 7.89 (d, J =
7
.9 Hz, 1H, Ar-H), 7.87 (d, J = 7.9 Hz, 1H, Ar-H), 7.78-7.73 (m, 1H, Ar-H), 7.49 (d, J = 7.5 Hz,
1
3
1H, Ar-H). C NMR (100 MHz, DMSO-d
6
): δ 182.9, 158.2, 146.9, 146.5, 145.5, 138.2, 135.6,
+
130.4, 130.3, 127.4, 127.3, 125.2, 123.8, 122.7, 117.5. MS (ESI): 249 (M+H , 100). These
8
a
assignments matched with those previously published.
6
2
8
-Hydroxy-6-(1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-one (6a). Yellow amorphous solid,
1
6
7.6 mg, 78% yield. H NMR (400 MHz, DMSO-d ): δ 11.13 (d, J = 1.6 Hz, 1H, NH), 8.55 (d, J =
.0 Hz, 1H, Ar-H), 8.32 (dd, J = 8.0, 1.6 Hz, 1H, Ar-H), 7.83 (dt, J = 1.5, 8.4 Hz, 1H, Ar-H), 7.67
(d, J = 7.7 Hz, 1H, Ar-H), 7.58 (t, J = 8.0 Hz, 1H, Ar-H), 7.55 (t, J = 8.8 Hz, 1H, Ar-H), 7.50 (d, J
=
7.7 Hz, 1H, Ar-H), 7.37-7.33 (m, 3H, Ar-H), 7.07 (d, J = 8.0 Hz, 1H, Ar-H), 6.99 (t, J = 7.8 Hz,
13
1
1
1
H, Ar-H), 6.88 (s, 1H, OH), 6.80 (t, J = 7.2 Hz, 1H, Ar-H). C NMR (100 MHz, DMSO-d ): δ
6
62.0, 159.5, 147.6, 138.6, 137.3, 136.2, 135.2, 130.2, 128.2, 127.9, 127.4, 126.9, 125.5, 125.0,
+
24.3, 121.8, 121.6, 119.8, 119.3, 116.7, 116.0, 112.2, 77.3. MS (ESI): 366 (M+H , 100), 388
+
(M+Na , 30). Anal calcd for C23
H
15
N
O
3 2
: C, 75.60; H, 4.14; N, 11.50. Found C, 75.32; H, 4.41; N,
11.25.
2
,8-Difluoro-6-(5-fluoro-1H-indol-3-yl)-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one
(6b).
1
Yellow amorphous solid, 29.2 mg, 70% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.26 (s, 1H,
NH), 8.52 (dd, J = 8.7, 4.5 Hz, 1H, Ar-H), 7.96 (d, J = 8.4 Hz, 1H, Ar-H), 7.77-7.69 (m, 2H, Ar-H),
7
1
.45-7.31 (m, 3H, Ar-H), 7.25 (d, J = 1.9 Hz, 1H, Ar-H), 7.18 (d, J = 8.9 Hz, 1H, Ar-H), 7.02 (s,
13
6
H, OH), 6.90 (t, J = 8.9 Hz, 1H, Ar-H). C NMR (100 MHz, DMSO-d ): δ 161.2 (d, J = 244.6
Hz), 161.1 (d, J = 246.5 Hz), 161.0, 158.6 (d, J = 3.3 Hz), 157.1 (d, J = 231.4 Hz), 144.3, 138.3 (d,
J = 8.0 Hz), 134.7 (d, J = 1.9 Hz), 134.0, 131.0 (d, J = 8.5 Hz), 126.6, 125.4 (d, J = 10.5 Hz),
123.5 (d, J = 24.0 Hz), 123.2 (d, J = 8.6 Hz), 118.5 (d, J = 8.4 Hz), 117.1 (d, J = 23.6 Hz), 115.5
(
d, J = 4.6 Hz), 113.2 (d, J = 9.8 Hz), 112.8 (d, J = 24.7 Hz), 111.8 (d, J = 13.9 Hz), 110.1 (d, J =
+
2
6.1 Hz), 105.4 (d, J = 24.0 Hz), 77.0 (d, J = 1.4 Hz). MS (ESI): 420 (M+H , 100). Anal calcd for
C H F N O : C, 65.87; H, 2.88; N, 10.02. Found C, 65.57; H, 3.14; N, 9.90.
2
3
12
3
3
2
2
,8-Dibromo-6-(5-bromo-1H-indol-3-yl)-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one
(6c).
1
Yellow amorphous solid, 43.5 mg, 72% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.37 (d, J = 2.2
Hz, 1H, NH), 8.43 (d, J = 8.6 Hz, 1H, Ar-H), 8.34 (d, J = 2.0 Hz, 1H, Ar-H), 7.99 (dd, J = 8.6, 2.0
Hz, 1H, Ar-H), 7.85 (s, 1H, Ar-H), 7.79 (dd, J = 8.6, 2.0 Hz, 1H, Ar-H), 7.69 (d, J = 2.0 Hz, 1H,
Ar-H), 7.62 (d, J = 8.6 Hz, 1H, Ar-H),, 7.34 (d, J = 8.6 Hz, 1H, Ar-H), 7.19 (dd, J = 8.6, 2.0 Hz,
13
1
6
H, Ar-H), 7.16 (d, J = 2.2 Hz, 1H, Ar-H), 7.08 (s, 1H, OH). C NMR (100 MHz, DMSO-d ): δ

Organic & Biomolecular Chemistry
Page 8 of 12
View Article Online
DOI: 10.1039/C8OB01216D
1
61.5, 158.2, 146.5, 138.2, 138.1, 137.6, 136.1, 133.4, 130.5, 129.0, 128.2, 127.1, 126.2, 124.4,
+
123.4, 123.3, 120.6, 119.8, 118.8, 114.9, 114.3, 112.0, 77.1. MS (ESI): 600 (M+H , 30), 602
+
+
(M+H , 100), 604 (M+H , 100). Anal calcd for C23
3 3 2
H12Br N O : C, 45.88; H, 2.01; N, 6.98. Found
C, 46.19; H, 2.25; N, 6.61.
6
-Hydroxy-2,8-diiodo-6-(5-iodo-1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-one (6d). Yellow
1
amorphous solid, 55.6 mg, 75% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.29 (s, 1H, NH), 8.51
(
s, 1H, Ar-H), 8.27 (s, 1H, Ar-H), 8.12 (s, 1H, Ar-H), 8.03 (s, 1H, Ar-H), 7.93 (s, 1H, Ar-H), 7.82
s, 1H, Ar-H), 7.43 (s, 1H, Ar-H), 7.32 (s, 1H, Ar-H), 7.22 (s, 1H, Ar-H), 7.07 (s, 1H, OH), 6.99 (s,
(
1
3
1
1
7
6
H, Ar-H). C NMR (100 MHz, DMSO-d ): δ 161.4, 158.1, 146.9, 143.8, 139.2, 138.1, 138.0,
36.4, 135.1, 133.8, 130.2, 129.8, 129.6, 128.0, 125.7, 123.5, 118.9, 114.8, 114.7, 93.3, 92.1, 83.3,
+
7.0. MS (ESI): 744 (M+H , 100). Anal calcd for C23
H
12
I
3
N
O
3 2
: C, 37.18; H, 1.63; N, 5.65. Found
C, 37.43; H, 2.96; N, 5.52.
6
-Hydroxy-2,8-dimethyl-6-(5-methyl-1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-one
(6e).
1
Yellow amorphous solid, 33.6 mg, 83% yield. H NMR (400 MHz, DMSO-d
6
): δ 10.95 (s, 1H,
NH), 8.41 (s, 1H, Ar-H), 8.10 (s, 1H, Ar-H), 7.64 (s, 1H, Ar-H), 7.56 (s, 1H, Ar-H), 7.34 (s, 1H,
Ar-H), 7.26-7.21 (m, 3H, Ar-H), 6.85 (s, 1H, Ar-H),, 6.82 (s, 1H, Ar-H),, 6.75 (s, 1H, OH), 2.48 (s,
1
3
3
1
1
H, CH ), 2.31 (s, 3H, CH ), 2.16 (s, 3H, CH ). C NMR (100 MHz, DMSO-d ): δ 161.3, 159.3,
3 3 3 6
45.7, 137.6, 136.7, 136.4, 136.3, 136.2, 135.6, 130.5, 128.0, 127.5, 126.3, 125.8, 125.3, 124.2,
+
23.1, 121.5, 119.5, 116.4, 115.7, 111.8, 77.3, 21.8, 21.4, 21.3. MS (ESI): 408 (M+H , 100). Anal
21 3 2
calcd for C26H N O : C, 76.64; H, 5.19; N, 10.31. Found C, 76.57; H, 5.39; N, 9.96.
6
-Hydroxy-2,8-dimethoxy-6-(5-methoxy-1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-one (6f).
1
Yellow amorphous solid, 39.5 mg, 87% yield. H NMR (400 MHz, DMSO-d ): δ 10.92 (d, J = 2.3
6
Hz, 1H, NH), 8.45 (d, J = 7.8 Hz, 1H, Ar-H), 7.66 (d, J = 3.0 Hz, 1H, Ar-H), 7.60 (d, J = 8.9 Hz,
1
1
6
H, Ar-H), 7.41 (dd, J = 8.9, 3.0 Hz, 1H, Ar-H), 7.22 (d, J = 8.0 Hz, 1H, Ar-H), 7.19 (d, J = 2.6 Hz,
H, Ar-H), 7.11 (dd, J = 8.9, 2.6 Hz, 1H, Ar-H), 7.05 (d, J = 2.6 Hz, 1H, Ar-H), 6.82 (s, 1H, OH),
13
3 3 3
.67-6.63 (m, 2H, Ar-H), 3.89 (s, 3H, OCH ), 3.75 (s, 3H, OCH ), 3.55 (s, 3H, OCH ). C NMR
(
100 MHz, DMSO-d ): δ 159.8, 158.8, 158.7, 158.6, 153.3, 141.9, 137.9, 132.5, 132.0, 129.7,
6
1
25.5, 124.9, 124.1, 122.6, 117.7, 115.8, 115.1, 112.7, 111.4, 111.2, 107.2, 102.3, 77.2, 56.2, 56.1,
+
55.5. MS (ESI): 456 (M+H , 100). Anal calcd for C26
21
H N
3
O
5
: C, 68.56; H, 4.65; N, 9.23. Found
C, 68.72; H, 4.70; N, 8.91.
6
6
-(5-Cyano-
1H-indol-3-yl)
-hydroxy-12-oxo-6,12-dihydroindolo[2,1-b]quinazoline-2,8-dicarbonitrile
(6g).
Yellow
1
amorphous solid, 23.4 mg, 53% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.27 (s, 1H, NH), 8.53
(
d, J = 4.4 Hz, 1H, Ar-H), 7.98 (s, 1H, Ar-H), 7.80-7.52 (m, 2H, Ar-H), 7.48-7.33 (m, 3H, Ar-H),
1
3
7
.26 (s, 1H, Ar-H), 7.18 (d, J = 9.6 Hz, 1H, Ar-H), 7.03 (s, 1H, OH), 6.95-6.87 (m, 1H, Ar-H). C
): δ 162.4, 162.3, 161.1, 160.0, 159.8, 158.6, 158.2, 155.9, 144.3,
38.4, 134.7, 134.0, 131.0, 126.6, 125.4, 123.7, 123.2, 118.5, 117.2, 115.5, 113.3, 112.7, 111.7,
NMR (100 MHz, DMSO-d
6
1
+
1
10.2, 105.5, 77.0. MS (ESI): 441 (M+H , 100). Anal calcd for C26
12 6 2
H N O : C, 70.91; H, 2.75; N,
1
3
9.08. Found C, 70.56; H, 2.94; N, 18.77.
,9-Difluoro-6-(6-fluoro-1H-indol-3-yl)-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one
(6h).
1
Yellow amorphous solid, 26.7 mg, 64% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.21 (s, 1H,
NH), 8.35 (dd, J = 8.8, 5.9 Hz, 1H, Ar-H), 8.25 (dd, J = 9.5, 2.3 Hz, 1H, Ar-H), 7.57-7.43 (m, 3H,
Ar-H), 7.34 (dd, J = 8.8, 5.9 Hz, 1H, Ar-H), 7.23 (dt, J = 9.9, 2.3 Hz, 2H, Ar-H), 7.12 (dd, J = 9.9,
13
2
.3 Hz, 1H, Ar-H), 6.95 (s, 1H, OH), 6.76 (dt, J = 9.5, 2.3 Hz, 1H, Ar-H). C NMR (100 MHz,

Page 9 of 12
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB01216D
DMSO-d
6
): δ 166.4 (d, J = 252.5 Hz), 163.2, 162.8 (d, J = 244.4 Hz), 159.2 (d, J = 234.9 Hz),
58.8, 149.7 (d, J = 13.2 Hz), 139.4 (d, J = 12.7 Hz), 137.2 (d, J = 12.6 Hz), 131.9 (d, J = 2.8 Hz),
30.0 (d, J = 11.0 Hz), 127.1 (d, J = 9.9 Hz), 125.2 (d, J = 3.0 Hz), 122.0, 121.5 (d, J = 10.1 Hz),
18.7 (d, J = 10.7 Hz), 116.5 (d, J = 23.5 Hz), 115.6, 114.1 (d, J = 22.6 Hz), 113.7 (d, J = 22.2 Hz),
1
1
1
+
108.0 (d, J = 24.3 Hz), 104.7 (d, J = 29.0 Hz), 98.1 (d, J = 25.4 Hz), 77.0. MS (ESI): 420 (M+H ,
100). Anal calcd for C23 : C, 65.87; H, 2.88; N, 10.02. Found C, 65.70; H, 2.97; N, 9.76.
3
12 3 3 2
H F N O
,9-Dichloro-6-(6-chloro-1H-indol-3-yl)-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one
(6i).
1
Yellow amorphous solid, 32.5 mg, 69% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.28 (s, 1H,
NH), 8.50 (s, 1H, Ar-H), 8.28 (s, 1H, Ar-H), 7.78 (s, 1H, Ar-H), 7.65 (s, 1H, Ar-H), 7.55 (s, 1H,
Ar-H), 7.47 (dd, J = 9.8, 5.9 Hz, 2H, Ar-H), 7.40 (s, 1H, Ar-H), 7.23 (s, 1H, Ar-H), 7.01 (s, 1H,
1
3
OH), 6.94 (s, 1H, Ar-H). C NMR (100 MHz, DMSO-d
6
): δ 162.8, 158.9, 148.6, 140.1, 139.4,
1
37.7, 134.7, 134.3, 128.9, 128.4, 127.5, 127.4, 127.0, 126.6, 125.7, 124.0, 122.2, 120.6, 119.8,
+
+
+
1
16.7, 115.4, 111.7, 77.0. MS (ESI): 468 (M+H , 100), 470 (M+H , 100), 472 (M+H , 30). Anal
calcd for C23 : C, 58.94; H, 2.58; N, 8.97. Found C, 59.06; H, 2.73; N, 8.66.
,10-Dichloro-6-(7-chloro-1H-indol-3-yl)-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one
3 3 2
H12Cl N O
4
(6j).
1
Yellow amorphous solid, 34.4 mg, 73% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.55 (s, 1H,
NH), 8.18 (dd, J = 7.8, 1.3 Hz, 1H, Ar-H), 7.97 (d, J = 7.8 Hz, 1H, Ar-H), 7.64 (t, J = 8.0 Hz, 2H,
Ar-H), 7.54 (t, J = 8.0 Hz, 2H, Ar-H), 7.44 (t, J = 7.8 Hz, 1H, Ar-H), 7.16 (s, 1H, Ar-H), 7.15 (d, J
13
=
8.0 Hz, 1H, Ar-H), 7.02 (s, 1H, OH), 6.96 (t, J = 8.0 Hz, 1H, Ar-H). C NMR (100 MHz,
DMSO-d
6
): δ 162.5, 157.6, 143.8, 139.7, 135.6, 135.4, 134.2, 132.9, 131.1, 129.3, 128.5, 127.1,
+
1
1
8
4
26.2, 125.8, 124.4, 124.3, 121.6, 121.4, 120.5, 120.4, 116.8, 116.4, 77.4. MS (ESI): 468 (M+H ,
+
+
00), 470 (M+H , 100), 472 (M+H , 30). Anal calcd for C H Cl N O : C, 58.94; H, 2.58; N,
23
12
3
3
2
.97. Found C, 58.79; H, 2.67; N, 8.82.
,10-Dibromo-6-(7-bromo-1H-indol-3-yl)-6-hydroxyindolo[2,1-b]quinazolin-12(6H)-one
(6k).
1
Yellow amorphous solid, 43.6 mg, 72% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.38 (d, J = 2.3
Hz, 1H, NH), 8.20 (dd, J = 7.9, 1.2 Hz, 1H, Ar-H), 8.13 (dd, J = 7.9, 1.3 Hz, 1H, Ar-H), 7.84 (d, J
7.9 Hz, 1H, Ar-H), 7.82 (d, J = 7.9 Hz, 1H, Ar-H), 7.61 (dd, J = 7.4, 1.2 Hz, 1H, Ar-H), 7.47 (t,
J = 7.9 Hz, 1H, Ar-H), 7.37 (t, J = 7.9 Hz, 1H, Ar-H), 7.30 (d, J = 7.1 Hz, 1H, Ar-H), 7.06 (d, J =
=
1
3
2
.3 Hz, 1H, Ar-H), 7.00 (s, 1H, OH), 6.94 (t, J = 7.9 Hz, 1H, Ar-H). C NMR (100 MHz,
DMSO-d
6
): δ 162.5, 157.5, 144.8, 139.9, 138.6, 137.6, 136.1, 135.7, 129.5, 128.9, 127.0, 126.8,
+
1
3
6
2
25.7, 124.7, 124.6, 124.3, 121.9, 121.6, 120.8, 116.9, 109.4, 104.6, 77.5. MS (ESI): 600 (M+H ,
+
+
0), 602 (M+H , 100), 604 (M+H , 100). Anal calcd for C H Br N O : C, 45.88; H, 2.01; N,
2
3
12
3
3
2
.98. Found C, 46.02; H, 2.31; N, 6.79.
,2''-Dimethyl-3'-oxo-(3,2':2',3''-terindoline)-1'-carbaldehyde (8a). Yellow solid, 285-288 °C (from
1
CH
2 2
Cl ), 30.6 mg, 73% yield. H NMR (400 MHz, DMSO-d
6
): δ 8.67 (s, 1H, CHO), 8.64 (d, J =
8
.3 Hz, 1H, Ar-H), 8.45-8.35 (bs, 2H, NH), 7.83 (d, J = 7.5 Hz, 1H, Ar-H), 7.77 (dt, J = 1.2, 8.3
Hz, 1H, Ar-H), 7.30 (t, J = 7.5 Hz, 1H, Ar-H), 7.21 (d, J = 7.5 Hz, 2H, Ar-H), 7.19 (d, J = 7.9 Hz,
1
H, Ar-H), 7.04 (t, J = 8.3 Hz, 2H, Ar-H), 6.93 (d, J = 8.1 Hz, 1H, Ar-H), 6.88 (d, J = 8.1 Hz, 1H,
1
3
3 3
Ar-H), 6.83 (d, J = 7.9 Hz, 1H, Ar-H), 2.08 (s, 3H, CH ), 2.04 (s, 3H, CH ). C NMR (100 MHz,
3
CDCl ): δ 195.9, 162.2, 150.0, 137.4, 135.2, 135.1, 134.9, 134.4, 127.6, 126.7, 125.3, 125.2, 123.4,
1
21.5, 121.4, 120.3, 120.2, 119.9, 119.8, 117.7, 110.6, 110.5, 107.9, 107.2, 71.3, 14.2, 14.0. MS
+
(
ESI): 420 (M+H , 100). Anal calcd for C H N O : C, 77.31; H, 5.05; N, 10.02. Found C, 77.16;
27
21
3
2
H, 5.40; N, 9.83.
5
,5',5''-Trichloro-2,2''-dimethyl-3'-oxo-(3,2':2',3''-terindoline)-1'-carbaldehyde (8b). Yellow solid,

Organic & Biomolecular Chemistry
Page 10 of 12
View Article Online
DOI: 10.1039/C8OB01216D
1
2
12-215 °C (from EtOAc/PE = 1:1), 35.2 mg, 67% yield. H NMR (400 MHz, CDCl
3
): δ 8.60 (d,
J = 8.7 Hz, 1H, Ar-H), 8.56 (s, 1H, CHO), 8.40 (s, 1H, NH), 8.37 (s, 1H, NH), 7.79 (d, J = 2.1 Hz,
1
H, Ar-H), 7.75 (dd, J = 8.7, 2.1 Hz, 1H, Ar-H), 7.16 (dd, J = 8.8, 2.8 Hz, 2H, Ar-H), 7.05-7.01 (m,
1
3
3
H, Ar-H), 6.86 (d, J = 1.7 Hz, 1H, Ar-H), 2.12 (s, 3H, CH
): δ 193.8, 161.5, 148.1, 137.5, 136.2, 135.7, 133.5, 133.4, 131.2, 128.2, 127.7, 126.2,
26.1, 125.0, 124.4, 122.4, 122.2, 119.2, 119.1, 118.9, 111.8, 111.7, 106.8, 106.3, 71.2, 14.3, 14.1.
3 3
), 2.06 (s, 3H, CH ). C NMR (100
MHz, CDCl
3
1
+
+
+
MS (ESI): 522 (M+H , 100), 524 (M+H , 100), 526 (M+H , 30). Anal calcd for C H Cl N O : C,
27
18
3
3
2
62.03; H, 3.47; N, 8.04. Found C, 62.35; H, 3.61; N, 7.73.
2
,2'',5,5',5''-Pentamethyl-3'-oxo-(3,2':2',3''-terindoline)-1'-carbaldehyde (8c). Yellow amorphous
1
solid, 37.3 mg, 81% yield. H NMR (400 MHz, DMSO-d
6
): δ 11.14 (s, 1H, NH), 11.09 (s, 1H,
NH), 8.39 (s, 1H, CHO), 8.37 (d, J = 8.3 Hz, 1H, Ar-H), 7.70 (dd, J = 8.5, 1.5 Hz, 1H, Ar-H), 7.62
s, 1H, Ar-H), 7.18 (t, J = 8.3 Hz, 2H, Ar-H), 6.81 (d, J = 8.3 Hz, 2H, Ar-H), 6.80 (s, 1H, Ar-H),
.53 (s, 1H, Ar-H), 2.38 (s, 3H, CH ), 2.14 (s, 3H, CH ), 2.11 (s, 3H, CH ), 2.02 (s, 3H, CH ), 1.94
). C NMR (100 MHz, DMSO-d ): δ 195.4, 161.5, 147.8, 138.8, 136.3, 135.5, 133.9,
(
6
3
3
3
3
1
3
(
s, 3H, CH
3
6
1
27.8, 127.6, 127.3, 126.8, 125.0, 123.6, 122.5, 122.4, 119.6, 118.7, 117.1, 111.2, 111.0, 106.2,
+
105.6, 71.8, 22.1, 22.0, 20.9, 13.9, 13.8. HRESIMS calcd for [C30
H
27
N O
3 2
+ Na ] 484.20010
(100%), found 484.19823 (100%).
6
-Hydroxy-8-methoxy-6-(5-methoxy-1H-indol-3-yl)indolo[2,1-b]quinazolin-12(6H)-one
(10).
1
Yellow amorphous solid, 23.8 mg, 56% yield. H NMR (400 MHz, DMSO-d
6
): δ 10.97 (s, 1H,
NH), 8.46 (d, J = 8.8 Hz, 1H, Ar-H), 8.30 (dd, J = 7.9, 1.2 Hz, 1H, Ar-H), 7.84 (dt, J = 1.2, 8.4 Hz,
H, Ar-H), 7.68 (d, J = 7.9 Hz, 1H, Ar-H), 7.59 (t, J = 7.9 Hz, 1H, Ar-H), 7.24 (d, J = 8.8 Hz, 1H,
Ar-H), 7.21 (d, J = 2.6 Hz, 1H, Ar-H), 7.14 (dd, J = 8.8, 2.6 Hz, 1H, Ar-H), 7.08 (d, J = 2.6 Hz,
1
1
3
1
H, Ar-H), 6.88 (s, 1H, OH), 6.75 (d, J = 2.3 Hz, 1H, Ar-H), 6.69 (dd, J = 8.8, 2.3 Hz, 1H, Ar-H),
1
3
3 3 6
.78 (s, 3H, OCH ), 3.58 (s, 3H, OCH ). C NMR (100 MHz, DMSO-d ): δ 162.0, 159.1, 158.8,
53.4, 147.6, 137.8, 135.1, 132.5, 132.0, 128.1, 127.8, 126.7, 125.5, 125.0, 121.7, 117.7, 115.6,
+
115.2, 112.8, 111.5, 111.2, 102.4, 77.5, 56.1, 55.6. MS (ESI): 426 (M+H , 100). Anal calcd for
C H N O : C, 70.58; H, 4.50; N, 9.88. Found C, 70.25; H, 4.73; N, 9.61.
2
5
19
3
4
Author Contributions
†
Huiwu Liao and Xiangjun Peng contributed equally to this work.
Acknowledgments
The authors are grateful to the National Natural Science Foundation of China (No: 21462002),
Natural Science Foundation of Jiangxi Province in China (No: 20161BAB203096), Innovation
training program for college students in Gannan normal university (2017) (No: 201710418009) for
financial support.
1
13
Supporting Information Available. H and C NMR spectra of compounds 1, 6, 8 and 10; and
X-ray crystallographic files (CIF) for 6a and 8a.
References
1
(a) G. Honda and M. Tabata, Planta Med. 1979, 36, 85−86; (b) H. Danz, S. Stoyanova, P.
Wippich, A. Brattstroem and M. Hamburger, Planta Med. 2001, 67, 411−416; (c) A. M.
Tucker and P. Grundt, ARKIVOC 2012, 546−569; (d) T. Murakami, A. Kishi, T. Sakurama, H.
Matsuda and M. Yoshikawa, Heterocycles 2001, 54, 957−966; (e) V. M. Sharma, P. Prasanna,
K. V. A. Seshu, B. Renuka, C. V. L. Rao, G. S. Kumar, C. P. Narasimhulu, P. A. Babu, R. C.
Puranik, D. Subramanyam, A. Venkateswarlu, S. Rajagopal, K. B. S. Kumar, C. S. Rao, N. V.

Page 11 of 12
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/C8OB01216D
S. Mamidi, D. S. Deevi, R. Ajaykumar and R. Rajagopalan, Bioorg. Med. Chem. Lett. 2002,
2, 2303−2307.
1
2
3
C. W. Jao, W. Lin, Y. Wu and P. Wu, J. Nat. Prod. 2008, 71, 1275−1279.
(a) P. P. Bandekar, K. A. Roopnarine, V. J. Parekh, T. R. Mitchell, M. J. Novak and R. R.
Sinden, J. Med. Chem. 2010, 53, 3558−3565; (b) A. K. Bhattacharjee, D. J. Skanchy, B.
Jennings, T. H. Hudson, J. J. Brendle and K. A. Werbovetz, Bioorg. Med. Chem. 2002, 10,
1
979−1982.
4
(a) J. M. Hwang, T. Oh, T. Kaneko, A. M. Upton, S. G. Franzblau, Z. Ma, S. N. Cho and P. Kim,
J. Nat. Prod. 2013, 76, 354−367; (b) L. A. Mitscher and W. Baker, Med. Res. Rev. 1998, 18,
3
63−374.
5
6
7
8
B. Batanero and F. Barba, Tetrahedron Lett. 2006, 47, 8201−8203.
E. S. Lee, J. G. Park and Y. Jahng, Tetrahedron Lett.2003, 44, 1883−1886.
C. Wang, L. Zhang, A. Ren, P. Lu and Y. Wang, Org. Lett. 2013, 15, 2982−2985.
(a) B. V. S. Reddy, D. M. Reddy, G. N. Reddy, M. R. Reddy and V. K. Reddy, Eur. J. Org. Chem.
2
015, 8018−8022; (b) J. Liang, S. E. Park, Y. Kwon and Y. Jahng, Bioorg. Med. Chem. 2012,
0, 4962−4967.
2
9
(a) A. Kumar, V. D. Tripathi and P. Kumar, Green Chem. 2011, 13, 51−54; (b) S. Yang, X. Li, F.
Hu, Y. Li, Y. Yang, J. Yan, C. Kuang and Q. Yang, J. Med. Chem. 2013, 56, 8321−8331; (c) F.
Jia, Z. Zhou, C. Xu, Y. Wu and A. Wu, Org. Lett. 2016, 18, 2942−2945; (d) B, Rai, R. D.
Shukla and A. Kumar, Green Chem. 2018, 20, 822−826.
10 For selected recent reviews, see: (a) T. Punniyamurthy, S. Velusamy and J. Iqbal, Chem. Rev.
2
005, 105, 2329−2364; (b) Z. Shi, C. Zhang, C. Tang and N. Jiao, Chem. Soc. Rev. 2012, 41,
381−3430; (c) S. E. Allen, R. R. Walvoord, R. Padilla-Salinas and M. C. Kozlowski, Chem.
3
Rev. 2013, 113, 6234−6458.
1 Y. Kuang, H. Rokubuichi, Y. Nabae, T. Hayakawa and M. Kakimoto, Adv. Synth. Catal. 2010,
52, 2635−2642.
1
1
3
2 For reviews on the application of TEMPO and its derivatives in organic synthesis, see: (a) R. A.
Sheldon, I. W. C. E. Arends, G. J. T. Brink and A. Dijksman, Acc. Chem. Res. 2002, 35,
7
74−781; (b) R. A. Sheldon and I. W. C. E. Arends, Adv. Synth. Catal. 2004, 346, 1051−1071;
c) J. M. Bobbitt, C. Bruckner and N. Merbouh, Org. React 2009, 74, 103−424; (d) C.
Bruckner, In Stable Radicals, R. G. Hicks, Ed.; John Wiley, United Kingdom, 2010, pp.
33−456; (e) L. Tebben and A. Studer, Angew. Chem. Int. Ed. 2011, 50, 5034−5068; (f) R.
(
4
Ciriminna and M. Pagliaro, Org. Process Res. & Dev. 2010, 14, 245−251; (g) S. Wertz and A.
Studer, Green Chem. 2013, 15, 3116−3134; (h) O. Garcia-Mancheno and T. Stopka, Synthesis
2
013, 45, 1602−1611; (i) Z. Zhou and L. Liu, Curr. Org. Chem. 2014, 18, 459−474; (j) Q. Cao,
L. M. Dornan, L. Rogan, N. L. Hughes and M. J. Muldoon, Chem. Commun. 2014, 50,
524−4543; (k) D. Xue and Y. Long, J. Org. Chem. 2014, 79, 4727−4734; (l) A. Gini, M.
4
Segler, D. Kellner and O. García Mancheño, Chem.-Eur. J. 2015, 21, 12053−12060.
3 (a) B. Yin, P. Huang, Y. Lu and L. Liu, RSC Adv. 2017, 7, 606−610; (b) Z. Deng, X. Peng, P.
Huang, L. Jiang, D. Ye and L. Liu, Org. Biomol. Chem. 2017, 15, 442−448; (c) L. Jiang, X.
Peng, P. Huang, Z. Chen and L. Liu, Tetrahedron 2017, 73, 1389−1396; (d) F. Lin, Y. Chen, B.
Wang, W. Qin and L. Liu, RSC Adv. 2015, 5, 37018−37022; (e) W. Qin, J. Zhu, Y. Kong, Y.
Bao, Z. Chen and L. Liu, Org. Biomol. Chem. 2014, 12, 4252−4259; (f) Y. Bao, J. Zhu, W. Qin,
Y. Kong, Z. Chen, S. Tang and L. Liu, Org. Biomol. Chem. 2013, 11, 7938−7945; (g) W. Qin,
1

Organic & Biomolecular Chemistry
Page 12 of 12
View Article Online
DOI: 10.1039/C8OB01216D
Q. Chang, Y. Bao, N. Wang, Z. Chen and L. Liu, Org. Biomol. Chem. 2012, 10, 8814−8821; (h)
W. Qin, Q. Chang, H. Luo, Y. Bao, Z. Chen and L. Liu, Curr. Org. Synth. 2013, 10, 492−499.
4 (a) Y. Li, K. Ji, H. Wang, S. Ali and Y. Liang, J. Org. Chem. 2011, 76, 744−747; (b) Y. Li, W.
Wang, S. Yang, B. Li, C. Feng and Z. Shi, Chem. Commun. 2010, 46, 4553−4555.
5 (a) A. Gazit, N. Osherov, I. Posner, P. Yaish, E. Poradosu, C. Gilon and A. Levitzki, J. Med.
Chem. 1991, 34, 1896−1907; (b) S. Dilber, M. Saban, J. Jelaca, A. Gelineo, L. Arsenijevic and
M. Bogavac, Pharmazie 1989, 44, 649−650; (c) A. Wetzel and F. Gagosz, Angew. Chem. Int.
Ed. 2011, 50, 7354−7358; (d) C. V. S. Kumar, V. G. Puranik and C. V. Ramana, Chem. Eur. J.
1
1
2
012, 18, 9601−9611.
6 (a) J. Liu, Z. Jiang, R. Wang, Y. Zheng, J. Chen, X. Zhang and Y. Ma, Org. Lett. 2007, 9,
127−4129; (b) J. Lee and J. S. Panek, Org. Lett. 2011, 13, 502−505; (c) H. Zheng, Z. Dong
1
4
and Q. Yu, Modern Study of Traditional Chinese Medicine, Vol.1, Xueyaun Press: Beijing,
China, 1997; Vol 1, pp. 328−334.
17 (a) J. Tatsugi, Z. Tong, Y. Izawa, ARKIVOC 2001, No. i, 67−73; (b) V. N. Burd, R. Bantleon,
K. H. van Pee, Appl. Biochem. Microbiol. 2001, 37, 248−250.