Selective synthesis of functionalized quinazolinone derivatives via biocatalysis

Article abstract of DOI:10.1016/j.mcat.2020.111261

A novel and efficient biocatalyzed methodology for the construction of functionalized quinazolinone derivatives via tandem / hydrolysis / decarboxylation / cyclization and transesterification reactions has been developed that works with a variety of 2-aminobenzamide and β-dicarbonyl compounds. This method requires mild conditions, and has demonstrated high catalytic activity, excellent yields, excellent chemoselectivity, and a broad substrate scope. Additionally, biocatalyzed decarboxylation does not require high temperatures or light activation, giving it a substantial advantage over alternative techniques. Most importantly, it offers a new example for the exploration of simple, convenient, and environmentally friendly synthetic routes utilizing enzymes in organic chemistry.

Full text of DOI:10.1016/j.mcat.2020.111261

Molecular Catalysis 498 (2020) 111261
Contents lists available at ScienceDirect
Molecular Catalysis
journal homepage: www.journals.elsevier.com/molecular-catalysis
Selective synthesis of functionalized quinazolinone derivatives
via biocatalysis
Jin Lan, Zhanggao Le*, Hongxia Li, Jia Meng, Bozhen Gong, Zongbo Xie*
Jiangxi Province Key Laboratory of Synthetic Chemistry, School of Chemistry, Biology and Material Science, East China University of Technology, 330013, Nanchang,
China
A R T I C L E I N F O
A B S T R A C T
Keywords:
A novel and efficient biocatalyzed methodology for the construction of functionalized quinazolinone derivatives
via tandem / hydrolysis / decarboxylation / cyclization and transesterification reactions has been developed that
works with a variety of 2-aminobenzamide and β-dicarbonyl compounds. This method requires mild conditions,
and has demonstrated high catalytic activity, excellent yields, excellent chemoselectivity, and a broad substrate
scope. Additionally, biocatalyzed decarboxylation does not require high temperatures or light activation, giving
it a substantial advantage over alternative techniques. Most importantly, it offers a new example for the
exploration of simple, convenient, and environmentally friendly synthetic routes utilizing enzymes in organic
chemistry.
Quinazolinone derivatives
Biocatalysis selective synthesis
Green chemistry
Decarboxylation
Tandem reaction
Introduction
for organic chemists.
Biocatalysis offers an alternative approach to the synthesis of func-
Quinazolinone derivatives are found in a wide variety of pharma-
ceutical compounds, and quinazolinone scaffolds have also been used in
the design of various commercially available drugs such as fenquizone
(used in the treatment of edema and hypertension), quinethazone (used
to treat hypertension), Iressa (clinically used against cell lung cancer
with ever increasing popularity), and doxazosin (used as an antihyper-
tensive agent) [1–6]. In view of their importance, several reports have
appeared in the literature describing the synthesis of these heterocycles.
Various catalysts such as cellulose-SO3H [7], thiamine hydrochloride
(VB1) [8], p-TSA [5], nanocomposites [9], ionic liquids [2,10], scan-
dium triflate (III) [11], β-cyclodextrin-SO3H [12], 2-morpholinoethane-
sulfonic acid [13], L-proline nitrate [14], SiO2-H3PW12O40 [15],
zirconium (IV) chloride [16], chiral phosphoric acids [17], ascorbic acid
[18], and metals [19,20] have been utilized to prepare these com-
pounds, as have catalyst-free methods [21] (Scheme 1). However, these
procedures either have limited scope for quinazolinone derivatives,
extended reaction times, or can cause potential metal and chemical
pollution. In addition, although several methods are available in the
literature for the synthesis of 2-arylquinazolinones, only a few methods
are available for the synthesis of 2,2-disubstituted quinazolin-4(1H)-one
derivatives. Therefore, the development of more practical and efficient
approaches toward quinazolinone derivatives remains an attractive task
tional compounds, demonstrating high efficiencies and increased envi-
ronmental friendliness. Enzymes have many fascinating features as
biodegradable green biocatalysts for organic synthesis, such as excellent
regio-, chemo-, and stereoselectivity, high catalytic efficiency, mild re-
action conditions, fewer byproducts, and fewer synthetic steps [22–24].
The well-studied hydrolases
α-chymotrypsin and Candida antarctica
lipase B (CALB) have demonstrated high activities that can be main-
tained in organic solvents [25,26]. Owing to these advantages and to
further explore the potential of such catalysts, we report the general and
direct selective synthesis of functionalized quinazolinone derivatives via
biocatalysis under neutral conditions (Scheme 1). To the best of our
knowledge, there is no report available on the selective synthesis of 2,
2-disubstituted quinazolin-4(1H)-one derivatives by C-C cleavage of
β-dicarbon compounds using tandem enzyme-catalyzed reactions.
Results and discussion
To assess the feasibility of the proposed reaction, a model system
using readily available and reasonably priced anthranilamide (1a) and
ethyl acetoacetate (2a) was investigated by varying enzyme sources, the
amount of enzyme, solvent, and reaction temperature to obtain the
optimum reaction conditions. The results of this investigation are
* Corresponding authors.
E-mail addresses: zhgle@ecut.edu.cn (Z. Le), zbxie@ecut.edu.cn (Z. Xie).
https://doi.org/10.1016/j.mcat.2020.111261
Received 6 August 2020; Received in revised form 2 October 2020; Accepted 14 October 2020
Available online 1 November 2020
2468-8231/© 2020 Elsevier B.V. All rights reserved.

J. Lan et al.
Molecular Catalysis 498 (2020) 111261
showed that moderate yields were obtained in H2O, cyclohexane, and
hexane, while low or no yields of 3a were obtained in other solvents
(Table 2, entries 1–10). Based on these results, hexane was selected as
the optimal solvent for the reaction. The catalyst amount was then
varied from 0 to 50 U under similar conditions (Table 1, entry 1; Table 2,
entries 10–15). When the amount of catalyst was 10 U, the yield of the
reaction was 75 % (Table 2, entry 12). An increase in the amount of
catalyst resulted in the yield remaining nearly constant (Table 2, entry
10, entries 13–15). Therefore, 10 U was selected as the optimal amount
for the reaction. Next, the potential of a two-phase reaction was
considered (Table 2, entries 16–21). The best results were obtained
when the ratio of hexane to water was 2:1, showing good conversion and
selectivity (Table 2, entry 17). After screening different molar ratios of
1a:2a (Table 2, entry 17, entries 22 ꢀ 26), a ratio of 1:2.5 was selected
after considering the atom economics of the reaction. Thereafter, the
effect of temperature was studied as it is a key influencing factor in most
biocatalytic reactions. For catalysis with CALB, it was discovered that
the initial choice of 50 ◦C (Table 2, entry 17) had been fortuitous, giving
the best results in terms of conversion and selectivity. It was also noticed
that when the reaction time was increased, the yield remained nearly
constant. The aforementioned results indicated that the optimal time for
this reaction was 40 h (Table 2, entry 32). In order to confirm the spe-
cific enzyme catalysis in the reaction, high temperature denatured CALB
(after treatment in water at 100 ◦C for 5days) was used to catalyze the
reaction, and no target products were generated as a result (Table 2,
entry 34). All the results clearly indicate that the catalytic ability of the
CALB is responsible for the model reaction.
Scheme 1. The synthesis routes of quinazolinone derivatives.
summarized in Table 1. Initially, the reaction was performed in ethanol
without a catalyst at 50 ◦C and was monitored via thin-layer chroma-
tography (TLC). However, these reaction conditions were ineffective.
Different enzyme sources were then chosen and the reaction was per-
formed under specific conditions for 48 h. No product was obtained
when enzymes such as amano lipase A from Aspergillus niger, pepsin
from porcine gastric mucosa, lipase from porcine pancreas, amano lipase
M from Mucor javanicus, and bovine trypsin and papain from papaya-
Next, the optimal conditions for the synthesis of 4d were ascertained.
As can be seen from the results in Table 1 (entry 8), α-chymotrypsin was
found to be the best catalyst for this reaction. Anthranilamide (1a) and
methyl 3-oxovalerate (2b) were selected as model substrates when
investigating the optimal reaction conditions, as shown in Table 3. When
screening the amount of enzyme, loadings of 2400–8000 U were found
to be equally reactive, and so considering the economics, 2400 U was
clearly preferable over 8000 U. Among the solvents evaluated (Table 3,
entry 2, entries 6 ꢀ 7), it was found that ethanol gave the highest per-
formance for this reaction, with a 77 % yield of the quinazolinone de-
rivative. Several parameters including temperature, molar ratio of
substrates, and time were then investigated to further optimize the re-
action conditions (Table 3, entries 8 ꢀ 14). The optimized reaction
conditions were found to be as follows: a temperature of 60 ◦C, a molar
ratio of 1:3, and a reaction time of 40 h (Table 3, entry 12). Under
latex were used (Table 1, entries 2–7). Surprisingly,
α-chymotrypsin
possessed excellent catalytic activity for the synthesis of 4d (Table 1,
entry 8), and it was even more pleasing that when CALB was used as a
catalyst, two quinazolinone derivatives, 3a and 4d, were formed in the
reaction (Table 1, entry 9). In order to optimize the reaction conditions
for the synthesis of the two products and to investigate the mechanism of
action, screening tests were conducted.
First, we examined the reaction conditions for the synthesis of 3a in
detail, and the results are presented in Table 2. CALB was selected as the
best catalyst for the synthesis of 3a; in addition, it was expected that the
solvent would be highly important for this reaction. Solvent screening
optimal conditions, denatured
α-chymotrypsin (Table 3, entry 15) were
also used as controls to demonstrate the specific catalytic effect of the
α
-chymotrypsin, which resulted in a yield of only trace. The results
clearly indicate that the catalytic ability of the
α-chymotrypsin is
responsible for the model reaction.
Table 1
With the optimized conditions in hand, the scope of the reaction used
to synthesize 3a was investigated by reacting anthranilamides possess-
ing various functional groups (1a–d) with different β-dicarbonyl com-
pounds (2a–h), as shown in Table 4. When the groups used were R1 = R2
= H, R3 = Me, the reaction proceeded smoothly to give the desired
product 3a in excellent yields, with an exception being when R4= t-Bu.
In this case, only a small amount of product was found, which may be
due to hydrolysis being more difficult when R4 = t-Bu. In addition, when
R1 = H, the yields decreased gradually as the length of the R3 chain
increased, although moderate yields were still achieved (Table 4, 3b and
3c). To further investigate the substrate scope, various substituted 2-
aminobenzylalcohols and β-dicarbonyl compounds were reacted sepa-
rately under the optimized conditions. Electron-withdrawing groups on
the 2-aminobenzamides allowed the reaction to proceed smoothly,
affording the corresponding products albeit with lower yields (Table 4,
3d). To our pleasure, substituting 2-aminobenzamides with electron-
donating groups resulted in considerably higher yields of quinazoli-
none derivatives (Table 4, 3e). Finally, an N-substituted 2-aminobenza-
mide was investigated, with the desired product 3f being obtained in a
Catalytic activities of different enzymes.a.
Yield(%)b
Entry
Catalyst (U)
3a
4d
1
2
3
4
5
6
7
8
9
No catalyst
NR
NR
NR
NR
NR
NR
NR
NR
16
NR
NR
NR
NR
NR
NR
NR
80
Amano lipase A from Aspergillus niger (300,000 U/g)
Pepsin from porcine gastric mucosa (601 U/mg)
Lipase from porcine pancreas (30ꢀ 90 U/mg)
Amano lipase M from Mucor javanicus (> = 10,000 U/g)
Papain from papayalatex (1.5ꢀ 10 U/mg)
Bovine trypsin (> = 2500 U/mg)
α
-chymotrypsin (800 U/mg)
Candida antarctica lipase B (CALB) (> = 2000 U/g)
36
a
Reaction conditions: 1a (0.2 mmol), 2a (0.5 mmol), enzyme (20 mg) in
ethanol (2 mL) for 48 h at 50 ◦C; b yields refer to isolated products, NR = no
reaction.
2

J. Lan et al.
Molecular Catalysis 498 (2020) 111261
Table 2
Optimization of the reaction conditions for the synthesis of 3a.a.
Entry
CALB loading (U)
Temp. (◦C)
Solvent
Time (h)
Molar ratio of 1a:2a
Yield (%)b
1
40
40
40
40
40
40
40
40
40
40
4
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
50
30
40
60
50
50
50
50
50
CH3CN
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
48
24
36
40
60
40
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:1
NR
trace
16
NR
NR
NR
NR
56
71
74
55
75
78
76
77
82
92
92
84
82
76
50
52
80
93
95
67
82
94
72
82
93
94
NR
2
CH3OH
3
Ethanol
4
DMSO
5
1, 4 - dioxane
THF
6
7
DMF
8
H2O
9
Cyclohexane
Hexane
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34c
Hexane
10
20
30
50
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
Hexane
Hexane
Hexane
Hexane
Hexane:H2O (1:1)
Hexane:H2O (2:1)
Hexane:H2O (3:1)
Hexane:H2O (4:1)
Hexane:H2O (6:1)
Hexane:H2O (9:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
Hexane:H2O (2:1)
1:1.5
1:2
1:3
1:4
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
1:2.5
a
Reaction conditions: 1a (0.2 mmol), 2a (0.2–0.5 mmol), enzyme (4–50 U) in solvent (2 mL) for 24–60 h at 30–60 ◦C; b yields refer to isolated product. CCALB
denatured by high temperature (in water at 100 ◦C for 5 days), NR = no reaction.
medium yield. A control experiment was also carried out to investigate
how the reaction proceeded, and it was found that hydrolysis was fol-
lowed by decarboxylation and then cyclization to form the target
product. This was demonstrated as the reaction produced 3a smoothly
when provided with acetone (Scheme 2, top), but was unable to produce
into two parts, both of which reacted with 2-aminobenzamide to form
two products in yields of 63 % (Table 5, 4q) and 37 % (Table 4, 3a). We
are currently studying why the enzyme causes bond breakages in these
substrates.
To further explore the potential of the catalyst system, tandem re-
actions using both enzymes were explored, as depicted in Scheme 3. The
previous reactions were used as templates, and the sequence of enzyme
addition and the reaction time were screened. Simultaneous addition of
–
the quinazolinone derivative by breaking the C C bond of a pre-
attached carbonyl compound (Scheme 2, bottom). Importantly, the
biocatalytic decarboxylation demonstrated in this paper does not
require high temperatures or light assistance, giving it an advantage
over other techniques.
both enzymes and addition of CALB a short time before α-chymotrypsin
led to two products (4a and 4b; Scheme 3a and b), which was confirmed
Having arrived at the optimized reaction conditions for the synthesis
of 4a, the generality of this reaction was also further examined using
various substituted 2-aminobenzamides and β-dicarbonyl compounds.
To our pleasure, both electron-donating and -withdrawing substitution
on 2-aminobenzamides and β-dicarbonyl compounds resulted in excel-
lent yields of quinazolinone derivatives (Table 5, 4a–4p). To our sur-
via HPLC (Fig. 1). On the other hand, when CALB was added after 24 h of
reaction with
α-chymotrypsin, only one product was obtained (4a,
Scheme 3c). The absence of the transester-exchange product may be due
to the higher activity of -chymotrypsin preventing the action of CALB.
α
To further explore the reaction sequence, 4a was used as the reaction
substrate, ethanol as the solvent, and CALB as the catalyst to explore
whether transesterification was possible. However, this was found to be
unfeasible (Scheme 3d). To our delight, the reactions of the two enzymes
could be successfully connected by extending the reaction time (Scheme
3e).
–
prise, when benzoylacetone was used as a substrate, a C C bond was
found to be broken (See Table 5) and one of the fragments produced the
corresponding quinazolinone derivative (75 % yield; Table 5,4q), but
the other fragment of the broken compound was not found to react with
2-aminobenzamide. Ethyl benzoylacetate was then selected as another
Having obtained the optimal conditions, the substrate range and
versatility of the combined enzyme-catalyzed tandem reaction were
investigated using different alcohols for the transesterification step. To
our surprise, when propanol was used as thetransesterification alcohol,
–
substrate to observe whether the presence of ester groups led to C
C
bond breakages, but none of the expected product was found. However,
when acetylacetone was used as the reaction substrate, it was cleaved
3

J. Lan et al.
Molecular Catalysis 498 (2020) 111261
Table 3
Optimization of the Reaction Conditions for 4a.a.
Entry
α-chymotrypsin loading (U)
Temp. (◦C)
Solvent
Time (h)
Molar ratio of 1a:2b
Yield (%)b
1
1600
2400
3000
4000
8000
2400
2400
2400
2400
2400
2400
2400
2400
2400
2400
50
50
50
50
50
50
50
40
60
60
60
60
60
60
60
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
DMSO
40
40
40
40
40
40
40
40
40
40
40
40
30
48
40
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:1.5
1:2.5
1:3
1:3
1:3
1:3
65
77
76
78
80
56
43
51
85
66
89
92
80
93
trace
2
3
4
5
6
7
CH3CN
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
Ethanol
8
9
10
11
12
13
14
15c
a
Reaction conditions: 1a (0.2 mmol), 2b (0.2–0.6 mmol), enzyme (1600–8000 U) in solvent (2 mL) for 30–48 h at 40–60 ◦C; b yields refer to isolated products. cα
-
chymotrypsin denatured by high temperature (in water at 100 ◦C for 5 days).
Table 4
Table 5
The substrate range of the CALB reaction.
The substrate range of the α-chymotrypsin reaction.
results reveal that the present selective biocatalyzed synthesis strategy is
feasible.
Finally, we attempted to determine the possible mechanism for this
reaction based on the control experiments and previous reports [25,
27–35], as illustrated in Scheme 4. In path a, catalysis with CALB leads
to hydrolysis, decarboxylation, and cyclization to form the target
product 3a. In path b, the proton of the amine group from o-amino-
benzamide can be extracted by His-57 and Asp-102. Meanwhile, the
carbonyl group of the β-ketoester is effectively activated by Ser-195. The
amine group of o-aminobenzamide attacks the carbonyl group of the
β-ketoester, which undergoes nucleophilic addition to form the inter-
mediate imino ester. The intermediate then forms the target product by
dehydration as the hydroxyl group of the intermediate captures the
Scheme 2. Control experiments demonstrating the mechanism of the
CALB reaction.
the target productwas found after the reaction (Table 6, 5a), but 18 % of
3b was also obtained (Table 4, 3b). When ethylene glycol was used as a
solvent, the tandem reaction proceeded smoothly, and 38 % of the
quinazolinone derivatives were obtained (Table 6, 5b). This indicates
that the substrate range of the tandem reaction is very wide. Thus, these
4

J. Lan et al.
Molecular Catalysis 498 (2020) 111261
Scheme 3. Tandem reactions using CALB and α-chymotrypsin.
Fig. 1. HPLC plots showing the presence of products 4a and 4b.
proton from His-57 and Asp-102, while
α-chymotrypsin is regenerated
Table 6
to complete the catalytic cycle. In path c, transesterification is first
catalyzed by CALB, and then path b is followed, generating the target
product via the tandem reaction.
The substrate range of the tandem reaction.
Conclusion
In summary, we described a novel strategy of hydrolysis, decarbox-
ylation, cyclization, and transesterification reactions to selectively syn-
thesize functionalized quinazolinone derivatives via biocatalysis under
mild conditions, with no high temperatures or light being required. In
addition, the two enzymes used performed distinct catalytic processes
5

J. Lan et al.
Molecular Catalysis 498 (2020) 111261
Declaration of Competing Interest
The authors reported no declarations of interest.
Acknowledgements
This project was supported by the National Natural Science Foun-
dation of China (No. 21462001), the Science and Technology Projects of
Jiangxi (No. 20192BBH80012).
Appendix A. Supplementary data
Supplementary material related to this article can be found, in the
online version, at doi:https://doi.org/10.1016/j.mcat.2020.111261.
References
Scheme 4. Proposed mechanisms for the reactions.
[1] J. Baselga, S.D. Averbuch, Drugs 60 (2000) 33–40.
[2] S. Das, S. Santra, S. Jana, G.V. Zyryanov, A. Majee, A. Hajra, Eur. J. Org. Chem.
2017 (2017) 4955–4962.
for consecutive reactions in the same vessel, and no special instruments
or apparatus were required. The quinazolinone derivatives were ob-
tained in good to excellent yields (up to 99 %) using a wide range of
substrates. This novel process provides a template for exploring simple,
environmentally friendly, and convenient synthetic routes utilizing en-
zymes in organic chemistry.
[3] S. Abdolmohammadi, S. Karimpour, Chin. Chem. Lett. 27 (2016) 114–118.
[4] S.K. Ghosh, R. Nagarajan, RSC Adv. 6 (2016) 27378–27387.
[5] M.-J. Hour, L.-J. Huang, S.-C. Kuo, Y. Xia, K. Bastow, Y. Nakanishi, E. Hamel, K.-
H. Lee, J. Med. Chem. 43 (2000) 4479–4487.
[6] O.M.O. Habib, H.M. Hassan, A. El-Mekabaty, Med. Chem. Res. 22 (2013) 507–519.
[7] B.V. Subba Reddy, A. Venkateswarlu, C. Madan, A. Vinu, Tetrahedron Lett. 52
(2011) 1891–1894.
[8] J. Devi, S.J. Kalita, D.C. Deka, Synth. Commun. 47 (2017) 1601–1609.
[9] J. Safari, S. Gandomi-Ravandi, J. Mol. Catal. A Chem. 390 (2014) 1–6.
[10] J. Chen, W. Su, H. Wu, M. Liu, C. Jin, Green Chem. 9 (2007) 972–975.
[11] J.X. Chen, H.Y. Wu, W.K. Su, Chin. Chem. Lett. 18 (2007) 536–538.
[12] J. Wu, X. Du, J. Ma, Y. Zhang, Q. Shi, L. Luo, B. Song, S. Yang, D. Hu, Green Chem.
16 (2014) 3210–3217.
Experimental
Candida antarctica lipase B immobilized on Immobead 150, recom-
binant from yeast (CALB, ≥2000 U/g) was purchased from Sigma-
Aldrich. Unless otherwise noted, all reagents were purchased from
commercial suppliers and used without further purification. General
experimental procedure for the synthesis of quinazolinones. Path A: A
10-mL stoppered bottle was filled with the required 2-aminobenzamide
(0.2 mmol), dicarbonyl compound (0.5 mmol), CALB (10U), 2 mL sol-
vent (ratio of hexane to water was 2:1) and oscillate in a constant
temperature shaker at 50 ◦C for 40 h. Path B: A 10-mL stoppered bottle
was filled with the required 2-aminobenzamide (0.2 mmol), dicarbonyl
[13] V.B. Labade, P.V. Shinde, M.S. Shingare, Tetrahedron Lett. 54 (2013) 5778–5780.
[14] H. Chandak, S. Bahekar, N. Dahake, P. Sarode, Synlett 26 (2015) 2575–2577.
[15] H. Alinezhad, E. Soleymani, M. Zare, Res. Chem. Intermed. 43 (2016) 457–466.
[16] M. Abdollahi-Alibeik, E. Shabani, Chin. Chem. Lett. 22 (2011) 1163–1166.
[17] W. Gong, X. Chen, H. Jiang, D. Chu, Y. Cui, Y. Liu, J. Am. Chem. Soc. 141 (2019)
7498–7508.
[18] G. Chandra Pariyar, B. Mitra, S. Mukherjee, P. Ghosh, ChemistrySelect 5 (2020)
104–108.
[19] S. Guo, Y. Li, L. Tao, W. Zhang, X. Fan, RSC Adv. 4 (2014) 59289–59296.
[20] S. Das, S. Sinha, D. Samanta, R. Mondal, G. Chakraborty, P. Brandao, N.D. Paul,
J. Org. Chem. 84 (2019) 10160–10171.
[21] Z.-B. Xie, S.-G. Zhang, G.-F. Jiang, D.-Z. Sun, Z.-G. Le, Green Chem. Lett. Rev. 8
(2015) 95–98.
compound (0.6 mmol),
α-chymotrypsin (2400U), 2 mL EtOH and
oscillate in a constant temperature shaker at 60 ◦C for 40 h. Path C: A 10-
mL stoppered bottle was filled with the required 2-aminobenzamide (0.2
mmol), dicarbonyl compound (0.6 mmol), CALB (10U), 2 mL alcohol
and oscillate in a constant temperature shaker at 60 ◦C for 60 h, then add
[22] A. Schmid, J.S. Dordick, B. Hauer, A. Kiener, M. Wubbolts, B. Witholt, Nature 409
(2001) 258–268.
[23] K. Li, T. He, C. Li, X.-W. Feng, N. Wang, X.-Q. Yu, Green Chem. 11 (2009) 777–779.
[24] C. Li, X.-W. Feng, N. Wang, Y.-J. Zhou, X.-Q. Yu, Green Chem. 10 (2008) 616–618.
[25] A. Kumar and P. Venkatesu, Chemical Reviews, 112, 4283-4307.
[26] M.-C. Parker, S.A. Brown, L. Robertson, N.J. Turner, Chem. Commun. (1998)
2247–2248, https://doi.org/10.1039/A806332J.
α
-chymotrypsin (2400U) oscillate in a constant temperature shaker at 60
◦C for 40 h. The eluent used for column chromatography was ethyl ac-
etate and petroleum ether, or chloroform and methanol.
[27] J. Uppenberg, N. Oehrner, M. Norin, K. Hult, G.J. Kleywegt, S. Patkar, V. Waagen,
T. Anthonsen, T.A. Jones, Biochemistry 34 (1995) 16838–16851.
[28] M. Kapoor, A.B. Majumder, J. Mukherjee, M.N. Gupta, Biocatal. Biotransformation
30 (2012) 399–408.
CRediT authorship contribution statement
[29] P.D. Tomke, V.K. Rathod, Ultrason. Sonochem. 27 (2015) 241–246.
[30] Y.-H. He, Y. Xiang, D.-C. Yang, Z. Guan, Green Chem. 18 (2016) 5325–5330.
[31] Y. Liu, R. Liu, Food Chem. Toxicol. 50 (2012) 3298–3305.
[32] D.M. Blow, J.J. Birktoft, B.S. Hartley, Nature 221 (1969) 337–340.
[33] Z.B. Xie, H.X. Li, L.S. Liu, J. Lan, Z.Y. Hu, Z.G. Le, Chin. J. Org. Chem. 39 (2019)
2632–2638.
Jin Lan: Conceptualization, Methodology, Investigation, Writing -
original draft. Zhanggao Le: Resources, Supervision. Hongxia Li:
Software, Formal analysis. Jia Meng: Validation, Investigation. Bozhen
Gong: Data curation. Zongbo Xie: Project administration, Writing -
review & editing, Supervision.
[34] X. Xin, M. Zhang, X.-F. Li, G. Zhao, J. Agric. Food Chem. 67 (2019) 11684–11693.
[35] X.-W. Feng, C. Li, N. Wang, K. Li, W.-W. Zhang, Z. Wang, X.-Q. Yu, Green Chem. 11
(2009) 1933–1936.
6