One-pot sequential multi-component reaction: Synthesis of 3-substituted indoles

Article abstract of DOI:10.1080/00397911.2018.1482352

Here, we have developed a 3-component one-pot sequential approach to 3-substituted indoles. The main advantages of this process are step economy, reduced waste, and operational simplicity. The method involves in situ generation of 3-indolylalcohols from t

Full text of DOI:10.1080/00397911.2018.1482352

Synthetic Communications
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One-pot sequential multi-component reaction:
Synthesis of 3-substituted indoles
Paran J. Borpatra, Bhaskar Deka, Basanta K. Rajbongshi, Mohit L. Deb &
Pranjal K. Baruah
To cite this article: Paran J. Borpatra, Bhaskar Deka, Basanta K. Rajbongshi, Mohit L. Deb &
Pranjal K. Baruah (2018): One-pot sequential multi-component reaction: Synthesis of 3-substituted
indoles, Synthetic Communications, DOI: 10.1080/00397911.2018.1482352
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https://doi.org/10.1080/00397911.2018.1482352
One-pot sequential multi-component reaction: Synthesis of
3-substituted indoles
Paran J. Borpatraa, Bhaskar Dekaa, Basanta K. Rajbongshib, Mohit L. Deba
Pranjal K. Baruaha
and
b
aDepartment of Applied Sciences, GUIST, Gauhati University, Guwahati, Assam, India; Department of
Chemistry, Cotton University, Guwahati, Assam, India
ABSTRACT
ARTICLE HISTORY
Received 14 April 2018
Here, we have developed
a 3-component one-pot sequential
approach to 3-substituted indoles. The main advantages of this pro-
cess are step economy, reduced waste, and operational simplicity.
The method involves in situ generation of 3-indolylalcohols from the
reaction of indoles and aldehydes in the presence of base. Further,
nucleophilic substitution of 3-indolylalcohols with various nucleo-
philes affords 3-substituted indole derivatives. The reaction does not
requires any hazardous and expensive metal catalyst. In addition, the
reaction is carried out in (1:1) ethanol–water which is considered as
environmentally benign solvent. On the other hand, nonsequential 3-
component reaction results in the formation of unwanted bisindolyl-
methanes.
KEYWORDS
Alkylideneindolenine inter-
mediate; 3-indolylalcohol;
one-pot; sequential
transformation;
3-substituted indole
GRAPHICAL ABSTRACT
Introduction
Sequential transformation is one of the most powerful tools in modern day synthetic
organic chemistry owing to its step economy.[1–3] Contrary to the traditional stepwise
approach, this method offers easier access to the more complex molecules from simple
and easily available starting materials. Some of the important examples of this method
include cascade,[4,5] domino,[6–8] and tandem reactions.[9,10] Different reactions knitted
into a sequence using one-pot process and multiple reagents and catalyst afford structur-
ally complex molecules. Over the years multicomponent reactions (MCRs) have gained
attention due to atom economy and found applications in combinatorial chemistry and
diversity-oriented synthesis.[11–16] Numerous pharmaceuticals and natural products were
synthesized through MCRs. The interest has also increased due to the replacement of
CONTACT Pranjal K. Baruah
baruah.pranjal@gmail.com; Mohit L. Deb
mohitdd.deb@gmail.com
Department
of Applied Sciences, GUIST, Gauhati University, Guwahati, Assam 781014, India.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data for this article can be accessed on the publisher’s website.
ß 2018 Taylor & Francis

2
P. BORPATRA ET AL.
Figure 1. 3-Substituted indoles having biological activity.
hazardous solvents with environment friendly solvents such as water, ethanol,
PEG, etc.[17,18]
Nitrogen containing heterocyles are known to have wide biological activity. Indole
derivatives are most important and naturally found in plants,[19] fungi,[20] and marine
organism.[21] They also exhibit several pharmacological activities,[22–24] act as free radical
scavengers and show a broad spectrum of antioxidant activity.[25–27] Furthermore, the
indole nucleus plays a vital component in several drugs. 3-Substituted indoles are versatile
intermediates for the synthesis of a wide range of indole compounds.[28–30] For example,
some bioactive 3-substituted indole derivatives are shown in Figure 1. Arvelexin [A]
shows potent activity against influenza virus A (H3N2).[31] Indolomycin [B] is a potent
antibacterial drug which is effective against Staphylococcus aureus and Helicobacter
pyroli.[32] 3-(a,a-Diarylmethyl)indole [C] which was synthesized in our laboratory is
found to be active against Methicillin-resistant S. aureus bacteria.[33] Indole-3-carbinol
has anticancer activity in many types of human prostate cancer cells.[34]
Results and discussions
The compounds in Figure 1 show excellent biological activities. Inspired by this, we
looked for an efficient method to synthesize such type of 3-substituted indole com-
pounds (see Scheme 1). In the very beginning, we planned to isolate 3-indolylalcohols
from the reaction of indole and aldehydes in the presence of a base in order to utilize
them as electrophiles. However, due to low stability of 3-indolylalcohols, we could not
isolate it. Therefore, it was decided to perform the nucleophilic substitution of 3-indoly-
lalcohols generated in situ from the 3-component reaction of indoles, aldehydes, and vari-
ous nucleophiles. We attempted to synthesize compound 4a by using our reported
method.[35] But we obtained bisindolylmethane (BIM). The use of Brønsted or Lewis acids
also offered solely BIM 5a. We then observed that the sequential addition of the substrates
catalyzed by base and acidified by an acid gave us good yield of 4a. Therefore, here we
report a sequential 3-component approach to 4 via 3-indolyl alcohols.
We began our model experiment with the reaction of indole (1a) and benzaldehyde (2a)
in the presence of base catalysts. After a careful screening of variety of bases/acids, we found
that sodium hydroxide (1equiv) in EtOH–H2O (1:1) as solvent at RT for 2 h and then add-
ing acetic acid (up to pH 5), nucleophile 3-methyl-1-phenyl-1H-pyrazol-5-amine (3a, 1
eqv.) and heating at 90 ꢀC for 1.5h is the optimum condition for the synthesis of 4a
(Table 1, entry 6). Lowering the NaOH loading decreased the product yield since all the

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3
Scheme 1. Synthesis of 3-substituted indoles.
Table 1. Optimization of the reaction condition.a
Temp. (ꢀC)
Time (h)
Yields (%)
Acidification
Entry
Base (eq)
(pH)
Solvent
EtOH
EtOH
DMF
H2O
1st step
2nd step
1st step
2nd step
4a
5a
1
2
3
4
5
6
7
8
NaOH (1.3)
NaOH (1.3)
NaOH (1.3)
NaOH (1.3)
NaOH (1.3)
NaOH (1.0)
NaOH (1.0)
NaOH (0.7)
NaOH (1.0)
NaOH (1.0)
NaOH (1.0)
KOH (1.0)
HCl (3)
HCl (4)
HCl (5)
HCl (5)
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
RT
90
90
90
90
90
90
90
90
90
100
80
90
90
90
90
90
2
2
2
2
2
2
2
2
2
2
2
2
4
5
5
4
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2
–
–
68
52
n.r.
76
11
5
18
14
16
12
10
8
22
n.r.
10
12
60
68
n.r.b
n.d.c
80
86
70
51
76
82
75
82
41
n.r.
n.d.
n.d.
–
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (6)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
AcOH (5)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:2)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
EtOH–H2O (1:1)
9
10
11
12
13
14
15
16
17d
18d
1.5
1.5
1.5
2
K2CO3 (1.0)
Et3N (1.0)
DABCO (1.0)
Cs2CO3 (1.0)
1.5
Cu(OAc)2ꢁH2O (10 mol %)
RT
RT
5
4
FeCl3ꢁ6H2O (10 mol %)
–
aReagents and conditions: Indole (1a, 1.0 mmol, 117 mg), benzaldehyde (2a, 1.0 mmol, 106 mg), 3-methyl-1-phenyl-1H-
pyrazol-5-amine (3a, 1.0 mmol, 173 mg). The 1st step was in RT and 2nd step was under heating. Products were puri-
fied by column chromatography and yields are for the isolated products.
bn.r.: no reaction.
cn.d.: not detected.
dThree component reaction using metal catalyst.
–NH proton of indole are not abstracted (Table 1, entry 8). On the other hand, increase of
NaOH did not improve the yield due to the increased formation of bisindolylmethane
(Table 1, entry 5). An increase in the ratio of water in the solvent mixture reduced the yield
of 4a (Table 1, entry 7). This is due to the increased formation of bisindolylmethanes.[36]
We also performed the reaction at higher and lower temperature for the second step. But

4
P. BORPATRA ET AL.
no improvement in the yield was observed (Table 1, entries 10–11). Using stronger acids in
the 2nd step favors bisindolylmethane formation. The KOH is almost as good as NaOH as
base catalyst (Table 1, entry 12). Interestingly, the bases like Et3N, DABCO, and Cs2CO3
did not produce our required product. We further used metal catalysts Cu(OAc)2.H2O and
FeCl3ꢁ6H2O for carrying out the reaction using nonsequential 3-component approach
(Table 1, entries 17–18). However, the reaction afforded only bisindolylmethane.
Having identified the optimized conditions, we next investigated the substrate scope
for the synthesis of 4 by subjecting various aldehydes and nucleophilic groups.
When alononitrile and imidazole were used as nucleophile, we obtained relatively less
yield of the product (4g and 4f, Scheme 2). 1,3-Dimethyl-6-aminouracil also produced
good yield (4h, Scheme 2). When N-substituted indoles were taken as nucleophiles we
obtained excellent yield of unsymmetrical bisindolylmethanes (4i and 4l–4o, Scheme 2).
Naphthols also afforded excellent yield of the products (4j–k, Scheme 2). Compounds 4
containing a wide range of substituents were obtained in good to excellent yields, as
summarized in Scheme 2. All the products were characterized by NMR spectroscopy as
well as analyzing X-ray structure of 4d (Figure 2). The compound was crystallized from
1:1 mixture of dichloromethane and petroleum ether by slow evaporation.
A plausible mechanism is proposed for the reaction based on the literature report
(Scheme 3).[37] The N–H proton of indole is abstracted by the base (NaOH) and the
indole anion thus formed attacks the aldehyde to generate the 3-indolylalcohol [X]. In
presence of acid, [X] then gets converted to alkylideneindolenine intermediates [Y].
This intermediate was then attacked by various nucleophiles to give the desired product.
Moreover, the intermediate [Y] also reacts with indole to furnish small amount of sym-
metrical bisindolylmethanes 5 as side product in some cases.
Conclusion
We here developed a 3-component one-pot sequential approach to 3-substituted indoles.
The reaction proceeds via the formation of 3-indolylalcohols. The reaction does not
require any hazardous metal catalyst. A plausible mechanism is proposed for
the reaction.
Experimental
Representative procedure for the synthesis of compound 4a
Indole (1a, 1 mmol, 117 mg), benzaldehyde (2a, 1 mmol, 106 mg), and NaOH (1 mmol,
40 mg) were taken in a round bottom flask. To this EtOH–H2O (1:1, 2 mL) as solvent
was added. The reaction mixture was stirred for 2 h at room temperature. The pro-
gress of the reaction was monitored by TLC. After completion of the first step, the
reaction mixture was acidified up to pH 5 by adding acetic acid, added 3-methyl-1-
phenyl-1H-pyrazol-5-amine (3a, 1 mmol, 173 mg) and then heated at 90 ꢀC for 1.5 h.
Solvent was removed under vacuum and extracted with dichloromethane (DCM). The
solvent was evaporated under vacuum and the crude product was purified by column
chromatography to obtain the desired product 4a[38] in the pure form. White solid,
1
(325 mg, 86%); H NMR (500 MHz, CDCl3): d 8.48 (bs, 1H, indole –NH), 7.51–7.49

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Scheme 2. The substrate scope for the synthesis of compound 4. Reagents and conditions: 1
(1 mmol), 2 (1 mmol), 3 (1 mmol). The first mentioned time indicates the reaction at room temperature
and the second one is under heating.
(m, 2H), 7.40–7.31 (m, 8H), 7.27–7.24 (m, 2H), 7.19 (t, J ¼ 7.9 Hz, 1H, Ar–H of
indole C6H benzene ring), 7.04 (t, J ¼ 7.8 Hz, 1H, Ar–H, indole C5H benzene ring),
6.62 (s, 1H, indole –C2H, heterocyclic ring), 5.53 (s, 1H, aliphatic –CH(Indole)(Ph)),
3.26 (bs, 2H, –NH2), 2.18 (s, 3H, –CH3); 13C NMR (125 MHz, CDCl3): d 148.2

6
P. BORPATRA ET AL.
Figure 2. ORTEP of compound 4d with 35% polarizability ellipsoids (CCDC 1815249).
Scheme 3. A plausible mechanism for the reaction.

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7
(pyarozole CNH2), 142.9 (pyarozole CCH3), 142.7 (C1Ph(pyrazole)), 138.4, 136.7,
129.3, 128.6, 128.5 (2C), 128.4, 126.8, 126.6, 126.4, 123.8, 123.7, 122.2, 119.6, 119.4,
117.5 (Indole C6H or C3H), 111.2 (Indole C6H or C3H), 102.9 (pyrazole –CHCNH2),
38.1 (C(Indole)(Ph)), 12.5 (CH3). The characterization data of all compounds could be
found in the supporting information provided with this article.
Acknowledgements
We acknowledge Dr. S. Karmakar for collecting single-crystal X-ray data and the Sophisticated
Analytical Instrumentation Facility (SAIF), Gauhati University, for use of the single-crystal X-ray
diffractometer. We acknowledge Gauhati University, Indian Institute of Technology, Guwahati
and National Chemical Laboratory, Pune for the NMR and Mass spectral facility.
Funding
MLD is thankful to Science and Engineering Research Board (SERB), India [Grant No. SB/FT/
CS-073/2014] for the financial support under “Fast Track” Scheme. PKB is also thankful to SERB,
India [Grant No. SB/FT/CS-100/2012] for the financial support. PJB and BD acknowledge
MHRD, Govt of India, for research fellowship under the TEQIP-III Project.
ORCID
Mohit L. Deb
Pranjal K. Baruah
http://orcid.org/0000-0002-6900-9316
http://orcid.org/0000-0002-5829-1440
References
[1] Ramon, D. J.; Yus, M. Asymmetric Multicomponent Reactions (AMCRs): The New
Frontier. Angew. Chem. Int. Ed. 2005, 44, 1602–1634. doi: 10.1002/anie.200460548.
[2] Cordova, A. The Direct Catalytic Asymmetric Mannich Reaction. Acc. Chem. Res. 2004,
37, 102–112. doi:10.1021/ar030231l.
€
[3] Domling, A. Recent Developments in Isocyanide Based Multicomponent Reactions in
Applied Chemistry. Chem. Rev. 2006, 106, 17–89. doi: 10.1021/cr0505728.
[4] Wang, K. K. Cascade Radical Cyclizations via Biradicals Generated from Enediynes,
Enyne-Allenes, and Enyne-Ketenes. Chem. Rev. 1996, 96, 207–222. doi: 10.1021/
cr950030y.
[5] Lu, L.-Q.; Chen, J. R.; Xiao, W. J. Development of Cascade Reactions for the Concise
Construction of Diverse Heterocyclic Architectures. Acc. Chem. Res. 2012, 45, 1278–1293.
doi: 10.1021/ar200338s.
[6] Hojo, D.; Tanaka, K. Rhodium-Catalyzed C–H Bond Activation/[4 þ 2] Annulation/
Aromatization Cascade to Produce Phenol, Naphthol, Phenanthrenol, and Triphenylenol
Derivatives. Org. Lett. 2012, 14, 1492–1495. doi: 10.1021/ol300234g.
[7] Piou, T.; Neuville, L.; Zhu, J. Spirocyclization by Palladium-Catalyzed Domino
Heck–Direct C–H Arylation Reactions: Synthesis of Spirodihydroquinolin-2-Ones. Org.
Lett. 2012, 14, 3760–3763. doi: 10.1021/ol301616w.
[8] Newman, S. G.; Howell, J. K.; Nicolaus, N.; Lautens, M. Palladium-Catalyzed
Carbohalogenation: Bromide to Iodide Exchange and Domino Processes. J. Am. Chem.
Soc. 2011, 133, 14916–14919. doi: 10.1021/ja206099t.

8
P. BORPATRA ET AL.
[9] Kang, D.; Park, S.; Ryu, T.; Lee, P. H. Gold-Catalyzed Hydrosilyloxylation Driving
Tandem Aldol and Mannich Reactions. Org. Lett. 2012, 14, 3912–3915. doi: 10.1021/
ol301660f.
[10] Gupta, S.; Kumar, B.; Kundu, B. Three-Component Tandem Reaction Involving Acid
Chlorides, Terminal Alkynes, and 2-Aminoindole Hydrochlorides: Synthesis of
a-Carboline Derivatives in Aqueous Conditions via Regioselective [3 þ 3]
Cyclocondensation. J. Org. Chem. 2011, 76, 10154–10162. doi: 10.1021/jo201994v.
[11] Domling, A.; Ugi, I. Multicomponent Reactions with Isocyanides. Angew. Chem. Int. Ed.
2000, 39, 3168–3210. doi: 10.1002/1521-3773(20000915)39:18 < 3168::AID-ANIE3168 >
3.0.CO;2-U.
[12] Tietze, L. F.; Beifuss, U. Sequential Transformations in Organic Chemistry: A Synthetic
Strategy with a Future. Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163. doi: 10.1002/
anie.199301313.
[13] Cane, D. E. Enzymatic Formation of Sesquiterpenes. Chem. Rev. 1990, 90, 1089–1103. doi:
10.1021/cr00105a002.
[14] Mayer, S. F.; Kroutiland, W.; Faber, K. Enzyme-initiated domino (cascade) reactions.
Chem. Soc. Rev. 2001, 30, 332–339. doi: 10.1039/B105493G.
€
[15] Domling, A.; Huang, Y. Piperazine Scaffolds via Isocyanide-Based Multicomponent
Reactions. Synthesis 2010, 2010, 2859–2883. doi: 10.1055/s-0030-1257906.
[16] Shiri, M. Indoles in Multicomponent Processes (MCPs). Chem. Rev. 2012, 112,
3508–3549. doi: 10.1021/cr2003954.
[17] Gu, Y. Multicomponent Reactions in Unconventional Solvents: state of the Art. Green
Chem. 2012, 14, 2091–2128. doi: 10.1039/C2GC35635J.
[18] Tundo, P.; Anastas, P.; Black, D. S.; Breen, J.; Collins, T.; Memoli, S.; Miyamoto, J.;
Polyakoff, M.; Tumas, W. Synthetic Pathways and Processes in Green Chemistry.
Introductory Overview. Pure Appl. Chem. 2000, 72, 1207–1228. doi: 10.1351/
pac200072071207.
[19] Nussbaum, F. V. Stephacidin B – A New Stage of Complexity within Prenylated Indole
Alkaloids from Fungi. Angew. Chem. Int. Ed. 2003, 42, 3068–3071. doi: 10.1002/
anie.200301646.
[20] Pindur, U.; Lemster, T. Advances in Marinenatural Productsof the Indole and Annelated
Indole Series: Chemical and Biological Aspects. Curr. Med. Chem. 2001, 8, 1681–1698.
doi: 10.2174/0929867013371941.
ꢀ
[21] Peng, W.; Switalska, M.; Wang, L.; Mei, Z.-W.; Edazawa, Y.; Pang, C.-Q.; El-Tantawy El-
Sayed, I.; Wietrzyk, J.; Inokuchi, T. Synthesis and in Vitro Antiproliferative Activity of
New 11-Aminoalkylamino-Substituted Chromeno[2,3-b]Indoles. Eur. J. Med. Chem. 2012,
58, 441–451. doi: 10.1016/j.ejmech.2012.10.023.
[22] Casapullo, A.; Bifulco, G.; Bruno, I.; Riccio, R. New Bisindole Alkaloids of the Topsentin
and Hamacanthin Classes from the Mediterranean Marine Sponge Rhaphisia lacazei. J.
Nat. Prod. 2000, 63, 447–451. doi: 10.1021/np9903292.
[23] Sundberg, R. J. The Chemistry of Indoles; Academic Press: New York, 1996.
[24] Basha, A. R. Indole Alkaloids; Harwood Academic: Chichester, 1998.
[25] Sreejith, P.; Beyo, R. S.; Divya, L.; Vijayasree, A. S.; Manju, M.; Oommen, O. V.
Triiodothyronine and Melatonin Influence Antioxidant Defense Mechanism in a Teleost
Anabas Testudineus (Bloch): In Vitro Study. Indian J. Biochem. Biophys. 2007, 44,
164–168.
~
[26] Estevao, M. S.; Carvalho, L. C.; Ribeiro, D.; Couto, D.; Freitas, M.; Gomes, A.; Ferreira,
L. M.; Fernandes, E.; Marques, M. M. Antioxidant Activity of Unexplored Indole
Derivatives: Synthesis and Screening. Eur. J. Med. Chem. 2010, 45, 4869–4878. doi:
10.1016/j.ejmech.2010.07.059.
[27] Grewal, P.; Mallaney, M.; Lau, K.; Sreedhara, A. Screening Methods to Identify Indole
Derivatives That Protect against Reactive Oxygen Species Induced Tryptophan Oxidation
in Proteins. Mol. Pharm. 2014, 11, 1259–1272. doi: 10.1021/mp4007375.

R
SYNTHETIC COMMUNICATIONSV
9
[28] Liu, Y.; Zhang, H. H.; Zhang, Y. C.; Jiang, Y.; Shi, F.; Tu, S. J. Organocatalytic
Enantioselective and (Z)-Selective Allylation of 3-Indolylmethanol via Hydrogen-Bond
Activation. Chem. Commun. 2014, 50, 12054–12057. doi: 10.1039/C4CC02056A.
[29] Li, Y.; Shi, F. Q.; He, Q. L.; You, S. L. N. Heterocyclic Carbene-Catalyzed Cross-Coupling
of Aldehydes with Arylsulfonyl Indoles. Org. Lett. 2009, 11, 3182–3185. doi: 10.1021/
ol9013238.
[30] Chen, C.; Feng, H. X.; Li, Z. L.; Cai, P. W.; Liu, Y. K.; Shan, L. H.; Zhou, X. L. A Highly
Efficient Route to C-3 Alkyl-Substituted Indoles via a Metal-Free Transfer Hydrogenation.
Tetrahedron Lett. 2014, 55, 3774–3776. doi: 10.1016/j.tetlet.2014.05.064.
[31] Liu, Y.-F.; Chen, M.-H.; Wang, X.-L.; Guo, Q.-L.; Zhu, C.-G.; Lin, S.; Xu, C.-B.;
Jiang, Y.-P.; Li, Y.-H.; Jiang, J.-D.; et al. Antiviral Enantiomers of a Bisindole Alkaloid
with a New Carbon Skeleton from the Roots of Isatis indigotica. Chin. Chem. Lett. 2015,
26, 931. doi: 10.1016/j.cclet.2015.05.052.
[32] (a) Kanamaru, T.; Nakano, Y.; Toyoda, Y.; Miyagawa, K.-I.; Tada, M.; Kaisho, T.; Nakao,
M. In Vitro and in Vivo Antibacterial Activities of TAK-083, an Agent for Treatment of
Helicobacter pylori Infection. Antimicrob. Agents Chemother. 2001, 45, 2455–2459. doi:
10.1128/AAC.45.9.2455-2459.2001. (b) Kanamaru, T.; Nakano, Y.; Toyoda, Y.; Miyagawa,
K.-I.; Tada, M.; Kaisho, T.; Nakao, M. Anti-Staphylococcal Activity of Indolmycin, a
Potential Topical Agent for Control of Staphylococcal Infections. J. Antimicrob.
Chemother. 2001, 45, 2455–2522. doi: 10.1093/jac/dkh352.
[33] Pegu, C. D.; Nasrin, S. B.; Deb, M. L.; Das, D. J.; Saikia, K. K.; Baruah, P. K. CAN-
Catalyzed Microwave Promoted Reaction of Indole with Betti Bases under Solvent-Free
Condition and Evaluation of Antibacterial Activity of the Products. Syn. Commun. 2017,
47, 2007–2014. doi: 10.1080/00397911.2017.1360912.
[34] Le, H. T.; Schaldach, C. M.; Firestone, G. L.; Bjeldanes, L. F. Diindolylmethane Is a Strong
Androgen Antagonist in Human Prostate Cancer Cells. J. Biol. Chem. 2003, 278,
21136–21145. doi: 10.1074/jbc.M300588200.
[35] Deb, M. L.; Borpatra, P. J.; Saikia, P. J.; Baruah, P. K. Base-Promoted Three-Component
One-Pot Approach to 3-(a,a-Diarylmethyl)Indoles via Arylation of 3-Indolylalcohols.
Synthesis 2016, 49, 1401–1409. doi: 10.1055/s-0036-15880098.
[36] Deb, M. L.; Bhuyan, P. J. An Efficient and Clean Synthesis of Bis(Indolyl)Methanes in a
Protic Solvent at Room Temperature. Tetrahedron Lett. 2006, 47, 1441–1443. doi: 10.1016/
j.tetlet.2005.12.093.
[37] (a) Deb, M. L.; Deka, B.; Saikia, P. J.; Baruah, P. K. Base-Promoted Three-Component
Cascade Approach to Unsymmetrical Bis(Indolyl)Methanes. Tetrahedron Lett. 2017, 58,
1999–2003. doi: 10.1016/j.tetlet.2017.04.032 (b) Uddin, M. I.; Buck, J. R.; Schulte, M. L.;
Tang, D.; Saleh, S. A.; Cheung, Y.-Y.; Harp, J.; Manning, H. C. Microwave-Assisted, One-
Pot Reaction of 7-Azaindoles and Aldehydes:
A Facile Route to Novel Di-7-
Azaindolylmethanes. Tetrahedron Lett. 2014, 55, 169–173. doi: 10.1016/j.tetlet.2013.10.143;
(c) Li, J.-T.; Dai, H.-G.; Xu, W.-Z.; Li, T.-S. An Efficient and Practical Synthesis of
Bis(Indolyl)Methanes Catalyzed by Aminosulfonic Acid under Ultrasound. Ultrason.
Sonochem. 2006, 13, 24–27. doi: 10.1016/j.ultsonch.2004.12.004.
[38] Deb, M. L.; Das, C.; Deka, B.; Saikia, P. J.; Baruah, P. K.; Base, P. T.-C. One-Pot Approach
to 3-(a,a-Diarylmethyl)Indoles via Arylation of 3-Indolylalcohols. Synlett 2016, 27,
2788–2794. doi: 10.1055/s-0036-1588887.