Decarboxylative aromatization of β-carbolines by using metal free catalysis and efficient synthesis of β-carboline derivatives

Article abstract of DOI:10.14233/ajchem.2015.19254

A new novel metal-free decarboxylative and aromatized β-carboline (5a-j) derivatives were synthesized by one-pot reaction. In all cases, resulting β-carboline derivatives with above 90 % yield.

Full text of DOI:10.14233/ajchem.2015.19254

Asian Journal of Chemistry; Vol. 27, No. 12 (2015), 4701-4702
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2015.19254
NOTE
Decarboxylative Aromatization of β-Carbolines by Using Metal Free
Catalysis and Efficient Synthesis of β-Carboline Derivatives
1,*
1
1
CHUNDURU SRINIVASA RAO , Ch. VENKATA RAMANA REDDY , B. RAMA DEVI ,
1
2
3
JYOTHI VANTIKOMMU , JYOTNA CHERUKURI and SHAKIL S. SAIT
1Department of Chemistry, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad-500 085, India
2Department of Chemistry, VNR Engineering College, Bachupally, Hyderabad-500 090, India
3Dr. Reddy's Laboratories Limited, Bachupally, Hyderabad-500 090, India
*Corresponding author: E-mail: chemistrycsr@gmail.com
Received: 20 April 2015;
Accepted: 26 May 2015;
Published online: 29 August 2015;
AJC-17533
A new novel metal-free decarboxylative and aromatized β-carboline (5a-j) derivatives were synthesized by one-pot reaction. In all cases,
resulting β-carboline derivatives with above 90 % yield.
Keywords: Harmine, Harmaline, Tetrahydroharmine, β-Carbolines.
Nitrogen atom contains polycyclic indolic compounds
have attracted a great deal of interest amongst synthetic
chemists over the years, partially because of their diverse
biological activities demonstrated1. Alkaloids are a group of
some 10,000 compounds that was originally defined by Carl
Friedrich Wilhelm Meissner in 1819 as natural compounds
similar in behaviour to alkalis and basic compounds2. The β-
carboline alkaloids, also known as harmala’s alkaloids, because
they were first isolated from Peganum harmala, are natural
products widely distributed in plants. Synthetic and naturally
occurring compounds containing the β-carboline nucleus
possess a large spectrum of important pharmacological
properties, including potent antitumor activity. Harmine (1),
harmaline (2) and tetrahydroharmine (3) alkaloids exist in eight
plant families and there are 64 different kinds of such alkaloids
have been separated and found to exhibit a variety of biological
activities3-8. The reported biological effects of this class of
compounds include antithrombotic9, sedative10,DNA-targeting
Because of their importance, previously a number of
methods have been developed for the synthesis of β-carbolines,
which involved aromatization, oxidation and decarboxylation
in a single step. This reaction is catalyzed by potassium
21
dichromate17, sulfur18, selenium dioxide19, TsOH20, CuCl2 ,
(NH4)2S2O822 and H2O2-peroxidase23. Based on the above
literature, in this paper, we have report the synthesis of novel
β-carboline derivatives employing PhI(OAc)2 as the catalyst.
All chemicals and reagents were obtained from Aldrich
(Sigma-Aldrich, St. Louis, MO, USA), Lancaster (AlfaAesar,
Johnson Matthey Company, Ward Hill, MA, USA) and were
used without further purification. Reactions were monitored
by TLC, performed on silica gel glassplates containing 60 F-
254 and visualization on TLC was achieved by UV light or
13
iodine indicator. 1H and C NMR spectra were recorded on
Gemini Varian-VXR-unity (300 MHz) or Bruker UXNMR/
XWIN-NMR (300 MHz) instruments. Chemical shifts (δ) are
reported in ppm downfield from internal TMS standard. ESI
spectra were recorded on Micro mass, Quattro LC using ESI+
software with capillary voltage 3.98 kV and ESI mode positive
ion trap detector. Melting points were determined with an
electrothermal melting point apparatus and are uncorrected.
General procedure for synthesis of β-carboline deriva-
tives (5a-j): To a solution of substituted 2,3,4,9-tetrahydro-
1H-pyrido[3,4-b]indole-3-carboxylic acids (1 mmol) in DMF
was added catalytic amount of PhI(OAc)2 (150 mg) and the
reaction mixture stirred at room temperature for 3 h under N2
properties11, anti-HIV12, and as well as suppression of CDK13,14
DNA topoisomerase15 and IrK16.
,
N
NH
Me
Tetrahydroharmine (3)
N
MeO
MeO
MeO
N
H
N
N
H
Me
Me
H
Harmaline (2)
Harmine (1)
Structures of alkaloids

4702 Rao et al.
Asian J. Chem.
atmosphere. After completion of reaction and extracted with
ethyl acetate (3 × 10 mL). Combined organic layer washed
with brine (10 mL) and dried over Na2SO4 and concentration
in vacuum and purified by column chromatography to afforded
respective compounds (5a-j) (Scheme-I).
144.2, 140.7, 138.9, 137.8, 129.5, 128.6, 127.1, 122.8, 120.5,
120.1, 119.1, 114.0, 111.4; m.f.: C17 H12O2N3 (289).
1
1-(4-Methoxyphenyl)-9H-pyrido[3,4-b]indole: H
NMR (300 MHz, CDCl3): δ 8.7 (s, 1H), 8.6 (d, J = 5.10 Hz,
1H), 8.3 (d, J = 8.10 Hz, 1H), 7.8 (m, 3H), 7.5 (m, 2H), 7.3
13
(m, 1H), 7.1 (d, J = 5.1 Hz, 2H), 3.9 (s, 3H); C NMR (75
MHz, CDCl3): δ 158.6, 141.5, 140.2, 137.3, 132.3, 130.0,
128.6, 128.1, 126.7, 120.0, 118.2, 113.0, 112.0, 111.2, 54.19;
m.f.: C18 H15ON2 (275).
The synthesis of these different substituted β-carboline
(5a-j) derivatives was conducted by the substituted β-
carboline-3-carboxylic acids in DMF solvent and PhI(OAc)2
at room temperature for 3 h (Scheme-I). Some of the compounds
(5a-i) were previously reported13. In all cases, resulting β-
carboline derivatives with above 90 % yield.
In conclusion, a new novel metal-free decarboxylative and
aromatized β-carboline derivatives were synthesized by one-
pot reaction. In all cases, resulting β-carboline derivatives with
> 90 % yield.
CO2H
PhI(OAc)2
N
NH
DMF, rt, 3 h
N
N
H
R
H
R
5a-j
4a-j
4a; R = H
4b; R = 3,4,5-trimethoxy
4c; R = 4-methoxy
4d; R = 3-methoxy
4e; R = 4-fluoro
4f; R = 4-chloro
4g; R = 4-nitro
4h; R= 4-trifluoromethyl
4i; R = 3,5-dimethoxy
4j; R = 4-bromo
5a; R = H
5b; R = 3,4,5-trimethoxy
5c; R = 4-methoxy
5d; R = 3-methoxy
5e; R = 4-fluoro
5f; R = 4-chloro
5g; R = 4-nitro
5h; R= 4-trifluoromethyl
5i; R = 3,5-dimethoxy
5j; R = 4-bromo
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13
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