An efficient nano CuO-catalyzed synthesis and biological evaluation of quinazolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones as potent antibacterial agents against Streptococcus lactis

Article abstract of DOI:10.1016/j.tetlet.2016.10.047

An environmentally benign nano CuO catalyzed strategy has been developed for one-pot synthesis of quinazolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones by use of hydrazine hydrate and ethidene diamine as nitrogen source. The antib

Full text of DOI:10.1016/j.tetlet.2016.10.047

Accepted Manuscript
An efficient nano CuO-catalyzed synthesis and biological evaluation of quina-
zolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones as
potent antibacterial agents against Streptococcus lactis
Jin Zhang, Pei Cheng, Yangmin Ma, Jia Liu, Zhi Miao, Decheng Ren, Chao
Fan, Ming Liang, Le Liu
PII:
S0040-4039(16)31361-2
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.10.047
TETL 48217
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
5 August 2016
12 October 2016
14 October 2016
Please cite this article as: Zhang, J., Cheng, P., Ma, Y., Liu, J., Miao, Z., Ren, D., Fan, C., Liang, M., Liu, L., An
efficient nano CuO-catalyzed synthesis and biological evaluation of quinazolinone Schiff base derivatives and
bis-2,3-dihydroquinazolin-4(1H)-ones as potent antibacterial agents against Streptococcus lactis, Tetrahedron
Letters (2016), doi: http://dx.doi.org/10.1016/j.tetlet.2016.10.047
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
An efficient nano CuO-catalyzed synthesis and
biological evaluation of quinazolinone Schiff base
derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones
as potent antibacterial agents against
Leave this area blank for abstract info.
Streptococcus lactis
Jin Zhang, Pei Cheng, Yangmin Ma, Jia Liu, Zhi Miao, Decheng Ren, Chao Fan, Ming Liang and Le Liu.

1
Tetrahedron Letters
An efficient nano CuO-catalyzed synthesis and biological evaluation of
quinazolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones
as potent antibacterial agents against Streptococcus lactis
Jin Zhang, Pei Cheng, Yangmin Ma, Jia Liu, Zhi Miao, Decheng Ren, Chao Fan, Ming Liang and Le Liu.
College of Chemistry & Chemical Engineering, Shaanxi University of Science & Technology; Key Laboratory of Auxiliary Chemistry & Technology for
Chemical Industry, Ministry of Education, Xi’an 710021, PR China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An environmentally benign nano CuO catalyzed strategy has been developed for one-pot
synthesis of quinazolinone Schiff base derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones by
use of hydrazine hydrate and ethidene diamine as nitrogen source. The antibacterial activity was
investigated using minimum inhibitory concentration (MIC) method against four bacterial
strains. Tests have shown that these derivatives have potential activity against Streptococcus
lactis. The structure-activity relationship of the antibacterial activity evaluation was also
explored.
Available online
Keywords:
Quinazolinone Schiff base
Bis-2,3-dihydroquinazolin-4(1H)-ones
Antibacterial activity
Hydrazine hydrate
2009 Elsevier Ltd. All rights reserved.
Ethidene diamine
Nitrogen-containing heterocycles are integral part of many
drug molecules, physiologically active natural products and
synthetic compounds. Quinazolinone represents a class of
annulated six-membered nitrogen heterocycles and a core
structural component in a variety of natural products and
synthesized compounds: febrifugine,1 7-hydroxyechinozolinone,2
1,2-dihydroxyrutaecarpine,3 N-methyl dihydroquinazolinone,4
spiro-oxindole dihydroquinazolinone,5 etc. These compounds
show extensively biological and pharmacological activity, for
instance, antitumor,6 anticytotoxicities,7 antipyretic,8 analgesic,9
diuretic,10 antihistamine,11 anti-depressant,12 and vasodilating
activities.13 Due to the importance of such activities of these
compounds, the synthesis of quinazolinone and its derivatives
have attracted considerable interests. The methodology for
synthesis of quinazolinone could be divided into four parts
according to different nitrogen sources: (a) the cascade reaction
of o-aminobenzamides with aldehydes,12-14 (b) the reductive
cyclization of 2-nitrobenzamides formamide to quinazolinones,15
(c) condensation of phenylhydrazine or benzoylhydrazine with
isatoic anhydride,16 (d) the condensation reaction of primary
amine or ammonium salts with aldehydes.17 Conventionally,
quinazolinone Schiff base derivatives were synthesized by
condensation of 2-aminobenzhydrazide with aromatic aldehyde.18
Bis-2,3-dihydroquinazolin-4(1H)-ones were synthesized by
condensation of isatoic anhydride and diamines in the presence
of KAlSO4·12H2O.19 However, the drawbacks of these protocols
were the multiply steps and low yield.
Based on our ongoing interest toward the design and synthesis
of novel heterocycles as antibacterial agents,20 we synthesized the
quinazolinone Schiff base derivatives
and bis-2,3-
dihydroquinazolin-4(1H)-ones by using hydrazine hydrate or
ethidene diamine as nitrogen source under mild conditions with
promoted nano CuO. All the synthesized compounds were
screened for four bacteria cultures antibacterial activity by use of
minimum inhibitory concentration (MIC).
In our previous work, the nano CuO effectively catalyzed the
condensation reactions isatoic anhydride, aromatic aldehydes
with aromatic amine at reflux temperature in EtOH.21 Hence, we
commenced our studies by investigating the condensation
reaction of isatoic anhydride (1), hydrazine hydrate (2) and
aromatic aldehydes (3), which was catalyzed by nano CuO in
EtOH at 78oC for 5 hours, and the ratio of reactants was 1: 0.5: 1.
Consequently, the desired product 4a can be obtained in 43%
yield, whereas the product 5 was synthesized in poor results due
to the steric hindrance. (Table 1, entry 1). When the ratio of
reactants changed to 1: 1: 2, the yield of product 4a was rising up
to 88% (Table 1, entry 2). Encouraged by this observation, we
investigated the effect of various nano particles on the model
reaction at reflux temperature in EtOH. The nano particles such
as nano Fe3O4, nano TiO2, and nano CeO2 (Table 1, entries 3-5)
resulted condensation reactions product 4a in lower yields
compared to the yield in the presence of nano CuO as catalyst.
Subsequently, other protonic solvents such as H2O also delivered
the product in 48% yield (Table 1, entry 6). Poor to moderate
———
 Corresponding author. Tel.: (+86) 029-86168312; fax: (+86) 029-86168312; e-mail: mym63@sina.com

2
Tetrahedron
with electron-donating and electron-withdrawing had no
yields were obtained when the reaction was performed in other
significant influences. It was delightful that the compounds such
as 4b, 4g, 4i, 4j, 4k, 4l, 4m, 4n and 4o synthesized for the first
time. All the compounds synthesized were characterized by
spectral analysis. The structure of 4g was confirmed by X-ray
single crystal diffraction analysis (Figure 1).
aprotic organic solvents such as dimethyl sulfoxide (DMSO),
dimethyl formamide (DMF), dioxane, acetonitrile and N-methyl-
2-pyrrolidone (NMP) (Table 1, entries 7-11). The loading of the
catalyst to the reaction was also screened (Table 1, entries 12-
14). The best result was obtained when 20 mol% nano CuO was
used (Table 1, entry 2). The desired product was obtained in 57%
yield, when the quantity of nano CuO was decreased to 10 mol%
(Table 1, entry 12). Increasing the proportion of nano CuO to 30
mol% did not enhance the yield further (Table 1, entry 13). Trace
amount of product was detected when the reaction was conducted
in the absence of nano CuO (Table 1, entry 14). The desired
product was obtained in 23% yield when CuO powder was used
as the catalyst for this protocol (Table 1, entry 15), which implied
nano CuO was crucial for this transformation.
Table 1 Optimization of reaction conditions for the formation of 4a
Figure 1. X-ray single crystal diffraction analysis of 4g
Table 2. The scope of the reaction for synthesis of various
dihydroquinazolinone Schiff basea
Catalyst
(mol%)
Temperature
(°C)
Ratio of
reactants
Yieldd
of 4a
Yield
of 5
Entry
Solvent a
nano CuO
(20)
e
1
2
EtOH
EtOH
EtOH
EtOH
EtOH
H2O
78
78
1:0.5:1 b
1:1:2 c
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
1:1:2
43%
88%
62%
71%
68%
48%
36%
42%
33%
14%
24%
57%
86%
-
-
nano CuO
(20)
-
-
-
-
-
-
-
-
-
-
-
-
-
nano Fe3O4
(20)
3
78
nano TiO2
(20)
4
78
Entry
1
R
H
R1
Compounds
Yieldb
83%
nano CeO2
(20)
5
78
nano CuO
(20)
6
100
100
100
100
80
C6H5-
nano CuO
(20)
7
DMSO
DMF
nano CuO
(20)
8
4a
4b
4c
4d
4e
4f
nano CuO
(20)
9
Dioxane
CH3CN
NMP
nano CuO
(20)
10
11
12
13
14
2
3
4
5
6
H
H
H
H
H
4-CHO-C6H4-
75%
81%
78%
87%
83%
nano CuO
(20)
100
78
nano CuO
(10)
EtOH
EtOH
EtOH
nano CuO
(30)
78
-
78
2-Br-C6H4-
CuO
powder
(20)
15
EtOH
78
1:1:2
23%
-
asolvent 5 mL.
bConditions: isatoic anhydride 1 (1.0 mmol), hydrazine hydrate 2 (0.5 mmol),
benzaldehyde 3a (1.0 mmol), 78 °C.
cConditions: isatoic anhydride 1 (1.0 mmol), hydrazine hydrate 2 (1 mmol),
benzaldehyde 3a (2.0 mmol), 78 °C.
4-CH3-C6H4-
4-CH3O-C6H4-
4-Cl-C6H4-
d Isolated yield.
e. Not detected.
With the optimized reaction conditions in hand, a variaty of
aromatic aldehydes and cyclohexanone were tested. Aromatic
aldehydes and heteroaromatic aldehyde were formed desired
products in excellent yields. Most of the aldehydes underwent
smooth transformation to the corresponding products in satisfied
yields (Table 2, entries 1-10). When cyclohexanone was used as
substrate,
the
desired
3'-(cyclohexylideneamino)-1'H-
spiro[cyclohexane-1,2'-quinazolin]-4'(3'H)-one was obtained
(Table 2, entry 8). When the reaction was performed in 5-
chlorine isatin anhydride and different substituted phenyl
aldehyde (Table 2, entries 11-15), the results showed the yield of
the unsubstituted isatoic anhydride was higher than the yield of
5-chlorine isatinan hydride, and the substrates at the C-2 position

3
7
H
H
3-pyridyl
cyclohexanone
2-furanyl
78%
82%
76%
51%
77%
70%
72%
77%
74%
Entry
1
R1
Compounds
Yieldb
75%
4g
4h
4i
8
4-CH3O-C6H4-
7a
7b
7c
7d
9
H
2
3
4
cinnamyl
4-pyridyl
2-furanyl
78%
62%
70%
10
11
12
13
14
15
H
4-iPr-C6H4-
4j
Cl
Cl
Cl
Cl
Cl
C6H5-
4k
4l
a Conditions: isatoic anhydride 1 (1.0 mmol), ethidene diamine 6 (0.5 mmol),
3 (1.0 mmol), nano CuO (20 mol%), reflux in EtOH at 78 °C for 5 hours.
4-CH3-C6H4-
b Isolated yields
3-pyridyl
4m
4n
4o
2-furanyl
4-Br-C6H4-
aConditions: isatoic anhydride 1 (1.0 mmol), hydrazine hydrate 2 (1.0 mmol),
3 (2.0 mmol), nano CuO (20 mol%), reflux in EtOH at 78 °C for 5 hours.
bIsolated yields.
To well understand the influence of the nitrogen source on
reaction yield better, the study was extended to ethidene diamine.
Substrates bearing 4-CH3O-C6H4-, cinnamyl, 4-pyridyl, 2-furnayl
moieties gave the desired bis-2,3-dihydroquinazolin-4(1H)-ones
in moderate to good yields (Table 3, entries 1-4). Notably, some
of these products were difficult to prepare using regular synthetic
methods from easily available substrates. It was worth
mentioning that compounds 7b, 7c, 7d were synthesized for the
first time.
Scheme 1. A plausible mechanism to the reaction
On the basis of our experimental results and by referring to
the literature,20-22 a plausible mechanism of the three components
condensation reaction was proposed in Scheme 1. Initially, the
carbonyl of the isatoic anhydride might be activated by nano
CuO particles, which underwent the nucleophilic attack of the
hydrazine hydrate and the decarboxylation to generate the 2-
aminobenzoyl hydrazide intermediate Ia. Ia was simultaneously
attacked by two aromatic aldehydes formed the intermediate IIa
Table 3 The scope of the reaction for synthesis various
bis-quinzolinones

4
Tetrahedron
with eliminating an equivalent amount of H2O. The
strong antibacterial activity against S.lactis. with MIC values
ranging from 16 to 32 μg/mL. The improvements of antibacterial
activity were likely due to the presence of halogen, which was
known to enhance lipophilicity and stability of the molecule.23
Changing the benzene ring to pyridine or furan ring resulted
highly active analogues 4g, 4i, 4m, 4n, 7c and 7d unexpectedly.
Substituents such as cyclohexyl (4h) and 4-isopropylphenyl (4j)
at C-2 position resulted strong antibacterial activity. From the
structure-activity relationship study of these compounds, it was
established that combination of quinazolinone with halogenated
phenyl, pyridyl and furanyl was favorable for the antibacterial
activity.
intramolecular nucleophilic addition of IIa generated the adduct
IIIa. Finally, the products 4 formed from IIIa by proton transfer.
As similar as the generation of the compound 4, the nucleophilic
nitrogen atom of ethidene diamine attacked on the carbonyl of
the isatoic anhydride to form the bisanthranilamide intermediate
Ib. The intermediate Ib was subject to a nucleophilic attack by
two aromatic aldehydes simultaneously to form the intermediate
IIb, which would undergo intramolecular cyclization to afford
intermolecular IIIb, then a proton transfer transformed IIIb into
the final product 7.
All the synthesized compounds were screened for their in
vitro antibacterial activity against two Gram-negative bacterial
strains: Escherichia coli (E. coli) and Pseudomonas aeruginosa
(P. aeruginosa) and two Gram-positive bacterial strains:
Streptococcus lactis (S. lactis) and Staphylococcus aureus (S.
aureus) using the minimum inhibitory concentration (MIC)
method with penicillin and streptomycin sulfate as the positive
controls. The MIC values were presented in Table 4.
In summary, we have demonstrated a concise, mild, and facile
protocol for the synthesis of quinazolinone Schiff base
derivatives and bis-2,3-dihydroquinazolin-4(1H)-ones with
hydrazine hydrate and ethidene diamine as nitrogen source. It
was found that the combination of quinazolinone with
halogenated phenyl, pyridyl and furanyl was favorable as the
potent antibacterial agents against S.lactis from the structure-
activity relationship study.
Table 4. Antibacterial activity of compounds 4a-4o and 7a-7d
MIC ( μg/mL)
Acknowledgements
Compounds
Gram-negative
P. aeruginosa
Gram-positive
S.lactis S. aureus
The work was supported by Scientific Research Project Item
for Key Laboratory of Shaanxi Province Education Department,
China (No. 2010JS056), Natural Science Basic Research Plan in
Shaanxi Province of China (No. 2014JQ2064), and the
Foundation for Young Scholars of Shaanxi University of Science
& Technology (No. BJ12-26).
E.coli
64
128
128
128
128
64
128
128
32
128
64
16
16
16
16
32
128
16
16
32
32
64
32
32
64
4
64
4a
4b
128
128
128
>256
128
64
128
128
128
128
128
128
64
4c
4d
4e
Supplementary Material
128
128
128
64
4f
Supplementary data associated with this article can be found
in the online version, at http://dx.doi.org/10.1016/j.tetlet.XXXX
4g
128
128
128
128
128
64
4h
128
128
128
128
128
128
128
128
128
128
128
4
4i
128
128
128
128
64
4j
References and notes
4k
1 Koepfly, J. B.; Mead, J. F.; Brockman, J. A., Jr. J. Am. Chem.
Soc.1837, 69, 1837.
2 Chaudhur, P. K. J. Nat. Prod. 1992, 55, 249-250.
3 Wattanapiromsakul, C.; Forster, P. I.; Waterman, P. G. Phytochemistry
2003, 64, 609-615.
4 Al-Rashood, S. T.; Aboldahab, I. A.; Nagi, M. N.; Abouzeid, L. A.;
Abdel-Aziz, A. A.; Abdel-Hamide, S. G.; Youssef, K. M.; Al-Obaid,
A. M.; El-Subbagh, H. I. Bioorg. Med. Chem.2006, 14, 8608-8621.
5 Bouley, R.; Ding, D.; Peng, Z.; Bastian, M.; Lastochkin, E.; Song, W.;
Suckow, M. A.; Schroeder, V. A.; Wolter, W. R.; Mobashery, S.;
Chang, M. J. Med. Chem.2016, 59, 5011-5021.
4l
4m
4n
128
>256
128
>256
128
64
128
64
4o
7a
128
128
64
7b
7c
7d
6 Li, L.; Dong, T.; Li, X.; Qiao, C. Biomed. Chromatogr. 1994, 8, 145-
147.
7 Liang, J. L.; Park, S. E.; Kwon, Y.; Jahng, Y. Bioorg. Med. Chem.
2012, 20, 4962-4967.
penicillin
-
-
streptomycin
sulfate
4
4
-
-
These data in Table 4 suggested that most of the compounds
presented more considerable potency against S.lactis. than other
bacteria. It was noted that compounds 4c, 4j, 4n, 4o and 7c
exhibited moderate inhibitory activities (MICs: 32μg/mL), and
compounds 4f-4j, 4l and 4m had significant activity against S.
lactis. (MICs: 16 μg/mL) which were comparable to the positive
control penicillin. The structure-activity relationship of the
antibacterial activity evaluation against S. lactis was also
explored. In the series of quinazolinone derivatives, the moieties
at the C-2 position were especially important for the activity.
Unsubstituted benzyl was moderately active against S.lactis.
(compounds 4a,4k and 7b). Introduction of formyl or methyl
(compounds 4b, 4d and 4l) at benzene ring did not improve the
activity. Replacement of methyl with methoxyl led to slight
increment in activity (compounds 4e and 7a). Interestingly,
compounds 4c, 4f and 4o with halogenated substituent exhibited
8 Maarouf, A. R.; El-Bendary, E. R.; Goda, F. E. Arch. Pharm. 2004,
337, 527-532.
9 Alagarsamy, V.; Parthiban, P. J. Heterocycl. Chem. 2014, 51, 1615-
1620.
10
Gokhan-Kelekci, N.; Koyunoglu, S.; Yabanoglu, S.; Yelekci, K.;
Ozgen, O.; Ucar, G.; Erol, K.; Kendi, E.; Yesilada, A. Bioorg. Med.
Chem. 2009, 17, 675-689.
11
Ito, S.; Ando, S.; Yamaguchi, K.; Funayama, N.; Yamamoto, T.;
Kuroiwa, Y.; Kubota, T.; Komoda, Y. Bioorg. Med. Chem. Lett. 1993,
3, 611-614.
12
13
14
Cheng, X.; Vellalath, S.; Goddard, R.; List, B. J. Am. Chem. Soc.
2008, 130, 15786-15787.
Sharma, M.; Pandey, S.; Chauhan, K.; Sharma, D.; Kumar, B.;
Chauhan, P. M. J. Org. Chem. 2012, 77, 929-937.
(a) Chen, J.; Su, W.; Wu, H.; Liu, M.; Jin, C. Green Chem. 2007,
9, 972-975; (b)Dhanunjaya Rao, A. V.; Vykunteswararao, B. P.;
Bhaskarkumar, T.; Jogdand, N. R.; Kalita, D.; Lilakar, J. K. D.;

5
Siddaiah, V.; Douglas Sanasi, P.; Raghunadh, A. Tetrahedron Lett.
2015, 56, 4714-4717.
J.; Zhao, J.; Wang, L.; Liu, J.; Ren, D.; Ma, Y. Tetrahedron 2016, 72,
936-943.
15
16
17
Yoo, C. L.; Fettinger, J. C.; Kurth, M. J. J. Org. Chem. 2005, 70,
6941-6943.
Yang, W.; Qiao, R.; Chen, J.; Huang, X.; Liu, M.; Gao, W.; Ding,
J.; Wu, H. J. Org. Chem. 2015, 80, 482-489.
21
(a) Ma, Y.; Ren, D.; Zhang, J.; Liu, J.; Zhao, J.; Wang, L.; Zhang,
F. Tetrahedron Lett. 2015, 56, 4076-4079; (b) Zhang, J.; Ren, D.; Ma,
Y.; Wang, W.; Wu, H. Tetrahedron 2014, 70, 5274-5282; (c) Zhang, J.;
Cheng, P.; Ma, Y.; Liu, J.; Miao, Z.; Fan, C. Chin. J. Org. Chem. 2016,
36, 1368-1374.
(a) Kumar, K. S.; Kumar, P. M.; Kumar, K. A.; Sreenivasulu, M.;
Jafar, A. A.; Rambabu, D.; Krishna, G. R.; Reddy, C. M.; Kapavarapu,
R.; Shivakumar, K.; Priya, K. K.; Parsa, K. V.; Pal, M. Chem.
Commun. (Camb) 2011, 47, 5010-5012; (b) Avalani, J. R.; Patel, D. S.;
Raval, D. K. J. Mol. Catal. B: Enzym. 2013, 90, 70-75; (c) Santra, S.;
Rahman, M.; Roy, A.; Majee, A.; Hajra, A. Catal. Commun. 2014, 49,
52-57; (d) Santra, S.; Bagdi, A. K.; Majee, A.; Hajra, A. RSC Adv.
2013, 3, 24931-24935; (e) Ramamohan, M.; Raghavendrarao, K.;
Sridhar, R.; Nagaraju, G.; Chandrasekhar, K. B.; Jayapraksh, S.
Tetrahedron Lett. 2016, 57, 1418-1420; (f) Shaterian, H. R.; Oveisi, A.
R.; Honarmand, M. Synth. Commun. 2010, 40, 1231-1242.
Wang, X. S.; Sheng, J.; Lu, L.; Yang, K.; Li, Y. L. ACS Comb.
Sci. 2011, 13, 196-199.
22
(a) Lu, J.; Gong, X.; Yang, H.; Fu, H. Chem. Commun. 2010, 46,
4172; (b) Kumar, P.; Singh, A. K.; Bahadur, V.; Len, C.; Richards, N.
G. J.; Parmar, V. S.; Van der Eycken, E. V.; Singh, B. K. ACS
Sustainable Chem. Eng. 2016, 4, 2206-2210; (c) Safari, J.; Gandomi-
Ravandi, S. J. Mol. Catal. A: Chem. 2013, 371, 135-140; (d) Rambabu,
D.; Kiran Kumar, S.; Yogi Sreenivas, B.; Sandra, S.; Kandale, A.;
Misra, P.; Basaveswara Rao, M. V.; Pal, M. Tetrahedron Lett. 2013,
54, 495-501.
23
Kirk, K. L. J. Fluorine Chem. 2006, 127, 1013-1029.
18
19
(a) Mohammadi, A. A.; Tahery, S.; Askari, S. Arkivoc 2014, 2014,
310-318; (b) Mohammadi, A. A.; Taheri, S.; Askari, S.; Ahdenov, R. J.
Heterocycl. Chem. 2015, 52, 1871-1875.
Click here to remove instruction text...
20
(a) Zhang, J.; Liu, J.; Ma, Y.; Ren, D.; Cheng, P.; Zhao, J.; Zhang,
F.; Yao, Y. Bioorg. Med. Chem. Lett. 2016, 26, 2273-2277; (b) Zhang,

6
Tetrahedron
Highlights
 Environmentally Friendly
 High efficiency
 Short reaction time
 Good
inhibitory
activity
to
Streptococcus lactis