Article
Ionic Liquid as an Efficient Medium for
the Synthesis of Quinoline Derivatives via
α-Chymotrypsin-Catalyzed Friedländer Condensation
Zhang-Gao Le 1,2, Meng Liang , Zhong-Sheng Chen , Sui-Hong Zhang and Zong-Bo Xie 1,2,
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2
*
1
Jiangxi 2011 Joint Center for the Innovative Mass Spectrometry and Instrumentation,
East China University of Technology, Nanchang 330013, China; zhgle@ecit.cn
2
School of Chemistry, Biology and Material Science, East China University of Technology, Nanchang 330013,
China; 13247718220@163.com (M.L.); zhshcheng@ecit.cn (Z.-S.C.); zsh18170400156@163.com (S.-H.Z.)
Correspondence: zbxie@ecit.edu.cn; Tel.: +86-791-8389-6550
*
Academic Editor: Hua Zhao
Received: 30 March 2017; Accepted: 4 May 2017; Published: 8 May 2017
Abstract: An efficient, convenient, and eco-friendly biocatalytic approach was developed for
the synthesis of quinoline derivatives via the
α-chymotrypsin-catalyzed Friedländer reaction.
Interestingly, -chymotrypsin exhibited higher catalytic activity in an ionic liquid (IL) aqueous
α
solution as compared to that observed in our previous relevant study, which was conducted using an
organic solvent, and a series of substrates gave similar excellent yields at lower reaction temperature
and under reduced enzyme-loading conditions.
Keywords: Friedländer reaction; quinolines; α-chymotrypsin; ionic liquid; biocatalysis; promiscuity
1
. Introduction
Quinoline derivatives are of great significance in medicinal chemistry [
display a broad range of excellent pharmacological activities, including anticancer [
anti-microbial [ ], antifungal [ ], anti-inflammatory [ ], and anti-platelet aggregation [7
1
] as they usually
], antiviral [ ],
] activities,
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which render them important drug intermediates. In addition, quinoline derivatives are valuable
synthons for the preparation of nano- and mesostructures with enhanced electronic and photonic
properties [8,9]. Various methods were developed for the synthesis of this class of compounds, such as
the Skraup synthesis [10], Doebner–Von Miller reaction [11], Combes synthesis [12], and the Friedländer
method [13]. Among these, the Friedländer method, which involves a condensation reaction
between a 2-aminoaryl ketone and a α-methylene ketone, is the most simple and straightforward.
Generally, this process can be carried out in the presence of base or acid catalysts to yield quinoline
derivatives. However, this method often suffers from poor selectivity, complicated procedures, or harsh
conditions [14,15] and is not practically feasible. Over recent years, biocatalysis has attracted increasing
interest in synthetic chemistry because it offers high efficiency and excellent selectivity and requires
mild reaction conditions; thus, biocatalysis has been identified as an eco-friendly and sustainable
alternative to traditional organic synthesis [16
promiscuity have been reported; for instance, hydrolase catalyzes unconventional reactions such as
the Aldol reaction [18 19], the Mannich reaction [20], and the Henry reaction [21]. In our previous
work, we demonstrated the first -chymotrypsin-catalyzed Friedländer condensation between a
-aminoaryl ketone and an -methylene ketone in an organic solvent [22], but the environmental
,17]. In particular, several valuable studies on enzymatic
,
α
2
α
problems related to the use of organic solvents are a matter of serious concern. Room-temperature ionic
liquids (RTILs), superior alternatives to organic solvents, have many potential benefits for biochemical
processes, especially where the reaction substrates and biocatalysts can be dissolved better, leading to