Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold as insecticidal/acaricidal agents

Article abstract of DOI:10.1016/j.bioorg.2018.07.034

In continuation of our program aimed at the development of natural product-based pesticidal agents, a series of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold were prepared, and their insecticidal and acaricidal activities were evaluated against Mythimna separata and Tetranychus cinnabarinus. Some compounds exhibited potent insecticidal and acaricidal activities. It suggested that R¹ as a nitro group and R² as a fluorine atom, were important for the insecticidal activity; R¹ as the electron-donating groups and R² as the methyl group, were necessary for the acaricidal activity.

Full text of DOI:10.1016/j.bioorg.2018.07.034

Accepted Manuscript
Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole scaffold as
insecticidal/acaricidal agents
Min Lv, Guangci Liu, Minghong Jia, Hui Xu
PII:
S0045-2068(18)30369-9
DOI:
https://doi.org/10.1016/j.bioorg.2018.07.034
YBIOO 2453
Reference:
Bioorganic Chemistry
To appear in:
Received Date:
Revised Date:
Accepted Date:
17 April 2018
18 July 2018
31 July 2018
Please cite this article as: M. Lv, G. Liu, M. Jia, H. Xu, Synthesis of matrinic amide derivatives containing 1,3,4-
thiadiazole scaffold as insecticidal/acaricidal agents, Bioorganic Chemistry (2018), doi: https://doi.org/10.1016/
j.bioorg.2018.07.034
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.

Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole
scaffold as insecticidal/acaricidal agents
a,1
a,1
a,
b,
Min Lv , Guangci Liu , Minghong Jiab, Hui Xu *
aResearch Institute of Pesticidal Design & Synthesis, College of Crop Protection/
Chemistry and Pharmacy, Northwest A&F University, Yangling Shaanxi 712100,
China
bBeijing Key Laboratory of Agricultural Product Detection and Control for Spoilage
Organisms
and
Pesticides,
College of
Food
Science
and
Engineering, Beijing University of Agriculture, Beijing 102206, China
*Corresponding author at: Research Institute of Pesticidal Design & Synthesis,
Northwest A&F University, Yangling 712100, Shaanxi Province, China. E-mail
address: orgxuhui@nwsuaf.edu.cn (H. Xu).
+86-29-87091952].
Tel: +86-29-87091952; Fax:
1These authors contributed equally to this work.
1

Abstract:
In continuation of our program aimed at the development of natural product-based
pesticidal agents, a series of matrinic amide derivatives containing 1,3,4-thiadiazole
scaffold were prepared, and their insecticidal and acaricidal activities were evaluated
against Mythimna separata and Tetranychus cinnabarinus. Some compounds
exhibited potent insecticidal and acaricidal activities. It suggested that R1 as a nitro
group and R2 as a fluorine atom, were important for the insecticidal activity; R1 as the
electron-donating groups and R2 as the methyl group, were necessary for the
acaricidal activity.
Keywords: Matrine; 1,3,4-Thiadiazole; Natural product-based; Insecticidal activity;
Acaricidal activity
2

1. Introduction
Mythimna separata Walker (oriental armyworm) and Tetranychus cinnabarinus
Boisduval (spider mite) are two typical and threatening pests of a wide range of crops
[1,2]. In recent years, lots of synthetic agrochemicals have been introduced to protect
crops from pests and enhance crop yields. However, extensive and unreasonable
applications of these agrochemicals have resulted in resistance in pest populations and
negative impacts on human health and environment [3]. Due to the advantages of
botanical pesticides, nowadays discovery and development of the potential
alternatives from plant-based natural products has attracted considerable interest
[4-12].
Matrine (1, Fig. 1) is a quinolizidine alkaloid isolated from the roots of Sophora
flavescens (Kushen), Sophora tonkinensis, and Sophora alopecuroides (Kudouzi) [13].
Compound 1 and its analogs showed a variety of biological properties such as
anticancer activity, anti-inflammatory activity, insecticidal activity, antimicrobial
activity, antiviral activity, etc [13-17]. Additionally, many molecules containing
1,3,4-thiadiazole scaffold (Fig. 1) exhibited some interesting biological activities such
as antioxidant activity, antitubercular activity, antimicrobial activity, acaricidal
activity, insecticidal activity, anticancer activity, etc [18-25]. Recently, we have
prepared a series of 14-formyl-15-aryloxy/methoxymatrines (2, Fig. 1) and
14-aryloxymethylylidenylmatrines (3, Fig. 1) by structural modification of matrine on
its lactam ring, and found that some compounds showed more promising pesticidal
activities than matrine against Mythimna separata and Plutella xylostella [26]. Based
3

upon the above results, and in continuation of our program aimed at the development
of new natural-product-based pesticidal agents [27-29], therefore, in this paper we
wanted to further investigate necessary of lactam ring by opening it, followed by
introduction of the 1,3,4-thiadiazole fragment. Their insecticidal and acaricidal
activities were evaluated against Mythimna separata and Tetranychus cinnabarinus.
Fig. 1. The chemical structures of matrine (1), its derivatives (2 and 3), matrinic acid,
1,3,4-thiadiazole, and matrinic amides containing 1,3,4-thiadiazole scaffold (7a–x).
2. Experimental section
General procedure for synthesis of compounds 7a–x.
A mixture of 1,3,4-thiadiazoles (4a-i, 0.28 mmol), N, N'-dicyclohexylcarbodiimide
(DCC, 0.2 mmol), 4-dimethylaminopyridine (DMAP, 0.04 mmol), and matrinic acids
(6a-c, 0.2 mmol) in dry DCM (10 mL) was stirred at room temperature. When the
4

reaction was complete according to TLC analysis, the mixture was diluted by DCM
(40 mL), washed by water (20 mL), 0.1 mol/L aq. HCl (20 mL), saturated aq.
NaHCO3 (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, concentrated in
vacuo, and purified by preparative thin-layer chromatography (PTLC) to give
compounds 7a–x in 26-78% yields. Exemplary data for compounds 7a and 7b are as
follows:
o
20
Data for 7a: Isolated yield = 54%, white solid, m.p. 206-208 C; [α] D = 3 (c
1
2.2 mg/mL, CHCl3); IR cm-1 (KBr): 3027, 2931, 1697, 1560, 1444, 1304, 755; H
NMR (500 MHz, CDCl3) δ: 7.87 (d, J = 7.0 Hz, 2H, Ar-H), 7.41-7.46 (m, 3H, Ar-H),
7.15-7.21 (m, 5H, Ar-H), 4.08 (d, J = 13.0 Hz, 1H), 3.05 (d, J = 13.0 Hz, 1H), 2.96 (d,
J = 10.5 Hz , 1H), 2.73-2.82 (m, 4H), 2.62 (t, J = 12.0 Hz, 1H), 2.34 (dd, J = 12.0, 3.5
Hz, 1H), 1.99-2.04 (m, 2H), 1.83-1.92 (m, 5H), 1.75-1.77 (m, 3H), 1.63-1.68 (m, 2H),
1.31-1.33 (m, 5H). HRMS (ESI): Calcd for C30H38ON5S ([M+H]+), 516.2792; Found,
516.2790.
Data for 7b: Isolated yield = 59%, white solid, m.p. 212-214 oC; [α] 20D = -3 (c
1
2.5 mg/mL, CHCl3); IR cm-1 (KBr): 3028, 2931, 1696, 1559, 1444, 1302, 739; H
NMR (500 MHz, CDCl3) δ: 7.68 (d, J = 10.0 Hz, 2H, Ar-H), 7.32 (t, J = 7.5 Hz, 1H,
Ar-H), 7.27 (s, 1H, Ar-H), 7.13-7.19 (m, 5H, Ar-H), 4.09 (d, J = 13.5 Hz, 1H), 3.02
(d, J = 13.5 Hz, 1H), 2.93 (d, J = 10.5 Hz, 1H), 2.72-2.83 (m, 4H), 2.59 (t, J = 12.0
Hz, 1H), 2.40 (s, 3H, Ar-CH3), 2.32 (dd, J = 11.5, 4.0 Hz, 1H), 2.00 (s, 2H),
1.81-1.94 (m, 5H), 1.75-1.77 (m, 3H), 1.62-1.68 (m, 2H), 1.30-1.33 (m, 5H). HRMS
(ESI): Calcd for C31H40ON5S ([M+H]+), 530.2948; Found, 530.2954
5

3. Results and discussion
3.1. Chemistry
Scheme 1. Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole
scaffold (7a–x).
As shown in Scheme 1, first, a series of aromatic carboxylic acids were
condensed with thiosemicarbazide to give 1,3,4-thiadiazoles (4a–i) [18]. Then
opening the lactam ring of compound 1 in the presence of 6 N aq. HCl, followed by
introduction of the different benzyl groups on the N-16 afforded compounds 5a–c.
Subsequently, hydrolysis of compounds 5a–c in the presence of NaOH produced
N-benzylmatrinic acids (6a–c) [30,31]. Finally, by reaction of N-benzylmatrinic
acids (6a–c) with 1,3,4-thiadiazoles (4a–i) in the presence of
6

N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP),
matrinic amide derivatives (7a–x) were obtained in 26-78% isolated yields [32].
1
Their structures were well characterized by H NMR, IR, optical rotation, HRMS
and mp (see Supplementary data).
3.2. Pesticidal activity
The insecticidal activity of compounds 1, 5a–c, 6a–c and 7a–x against the
pre-third-instar larvae of Mythimna separata was tested by leaf-dipping method
[32]. Toosendanin was used as a positive control. Leaves treated with acetone
alone were used as a blank control group. The symptoms of the treated M.
separata during three periods such as the larval stage, the pupation stage and the
adult stage, were observed in the same way as in our previous papers [29,32].
As shown in Table 1, among all derivatives, compounds 5c, 6c, 7e, 7h, 7n, 7q,
7w and 7x exhibited the insecticidal activity equal to or higher than that of the
positive control toosendanin. Especially compound 7w exhibited the most potent
pesticidal activity with the final mortality rate (FMR) of 65.5%; whereas the FMR
of their precusor (compound 1) was only 27.6%. To compounds 5a–c and 6a–c,
when R2 was a fluorine atom, the corresponding compounds 5c and 6c exhibited
more potent insecticidal activity than those containing other substituents (e.g.,
5a,b and 6a,b). For instance, the FMRs of 5c and 6c were 51.7% and 51.7%,
respectively; whereas the FMRs of 5a, 5b, 6a and 6b were 41.4%, 34.5%, 44.8%
and 41.4%, respectively. To compounds 7a–x, generally, when R1 was a nitro
group, the corresponding compounds showed more promising insecticidal activity
7

than those containing other substituents (e.g, 7e vs 7a–b and 7f–i; 7n vs 7j–m and
7o–r; 7w vs 7s–v and 7x). All in all, it was noteworthy that when R1 was a nitro
group, and R2 was a fluorine atom, among all derivatives, the corresponding
compound 7w showed the most potent insecticidal activity.
Table 1
Insecticidal activity of compounds 1, 5a–c, 6a–c and 7a–x against M. separata on
leaves treated at a concentration of 1 mg/mL.
Corrected mortality rate (% ± SD)
Compound
R1
R2
10 days
6.7 ± 3.3
10.0 ± 5.8
0 ± 0
20 days
13.8 ± 3.3
20.7 ± 3.3
10.4 ± 3.3
27.6 ± 5.8
24.2 ± 3.3
24.2 ± 3.3
31.1 ± 3.3
17.3 ± 0
35 days
/
/
H
1
27.6 ± 0
/
/
5a
5b
5c
6a
6b
6c
7a
7b
7c
7d
7e
7f
41.4 ± 3.3
34.5 ± 6.7
51.7 ± 3.3
44.8 ± 3.3
41.4 ± 3.3
51.7 ± 3.3
27.6 ± 5.8
27.6 ± 5.8
31.1 ± 3.3
41.4 ± 6.7
58.6 ± 5.8
44.8 ± 3.3
44.8 ± 6.7
51.7 ± 3.3
38.0 ± 5.8
31.1 ± 3.3
24.2 ± 3.3
27.6 ± 5.8
4-Me
4-F
H
/
16.7 ± 3.3
16.7 ± 6.7
23.3 ± 6.7
30.0 ± 0
/
/
4-Me
4-F
H
/
H
6.7 ± 3.3
13.3 ± 3.3
16.7 ± 3.3
13.3 ± 6.7
23.3 ± 3.3
30.0 ± 0
4-Me
3-Me
4-OMe
3-NO2
3-Cl
2-Cl
4-Cl
4-Br
H
H
17.3 ± 5.8
20.7 ± 3.3
20.7 ± 3.3
44.8 ± 3.3
27.6 ± 0
H
H
H
H
H
7g
7h
7i
13.3 ± 3.3
23.3 ± 3.3
13.3 ± 3.3
10.0 ± 0
27.6 ± 5.8
34.5 ± 3.3
17.3 ± 5.8
17.3 ± 0
H
H
4-Me
4-Me
4-Me
7j
4-Me
3-Me
7k
7l
13.3 ± 3.3
13.3 ± 3.3
13.8 ± 6.7
10.4 ± 3.3
8

4-OMe
3-NO2
3-Cl
2-Cl
4-Cl
4-Br
H
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-F
7m
16.7 ± 6.7
16.7 ± 3.3
13.3 ± 6.7
16.7 ± 3.3
13.3 ± 3.3
13.3 ± 3.3
13.3 ± 6.7
20.0 ± 5.8
23.3 ± 3.3
13.3 ± 3.3
23.3 ± 3.3
16.7 ± 3.3
10.0 ± 5.8
17.3 ± 5.8
31.1 ± 3.3
17.3 ± 0
31.1 ± 5.8
51.7 ± 3.3
34.5 ± 6.7
34.5 ± 3.3
48.3 ± 5.8
38.0 ± 5.8
34.5 ± 3.3
41.4 ± 3.3
44.8 ± 3.3
38.0 ± 5.8
65.5 ± 3.3
48.3 ± 5.8
48.3 ± 5.8
7n
7o
7p
17.3 ± 0
7q
27.6 ± 5.8
20.7 ± 3.3
17.3 ± 5.8
24.2 ± 3.3
34.5 ± 3.3
24.2 ± 3.3
38.0 ± 5.8
27.6 ± 5.8
27.6 ± 5.8
7r
7s
4-Me
3-Me
4-OMe
3-NO2
4-Br
/
4-F
7t
4-F
7u
4-F
7v
7w
4-F
4-F
7x
toosendanin
/
Table 2
Acaricidal activity of compounds 1, 5a–c, 6a–c and 7a–x against the female adults of
T. cinnabarinus at a concentration of 0.5 mg/mL.
Corrected mortality rate (% ± SD)
Compound
R1
R2
48 hours
10.4 ± 2.6
14.1 ± 3.1
17.4 ± 1.4
13.2 ± 0.6
24.0 ± 3.0
31.0 ± 0.7
19.0 ± 0.4
10.2 ± 3.2
9.7 ± 0.6
72 hours
23.4 ± 2.7
34.1 ± 2.7
38.5 ± 5.1
25.1 ± 1.3
52.2 ± 1.5
61.0 ± 2.1
49.8 ± 3.2
27.7 ± 1.8
34.9 ± 2.9
32.6 ± 3.4
39.6 ± 3.4
19.9 ± 1.5
/
/
H
1
/
5a
5b
5c
6a
6b
6c
7a
7b
7c
7d
7e
/
4-Me
4-F
H
/
/
/
4-Me
4-F
H
/
H
4-Me
3-Me
4-OMe
3-NO2
H
H
13.3 ± 2.2
18.5 ± 3.5
10.2 ± 1.1
H
H
9

3-Cl
2-Cl
4-Cl
4-Br
H
H
H
7f
11.2 ± 4.1
12.6 ± 2.3
17.5 ± 2.0
11.2 ± 1.5
11.2 ± 1.7
17.0 ± 1.4
17.1 ± 2.9
16.8 ± 4.3
12.7 ± 1.6
8.4 ± 2.5
24.5 ± 3.0
27.2 ± 2.8
30.7 ± 2.6
35.3 ± 1.8
22.3 ± 2.6
42.4 ± 3.3
41.0 ± 2.2
46.9 ± 2.8
26.4 ± 1.3
33.2 ± 2.7
32.8 ± 2.4
28.6 ± 1.4
26.5 ± 2.6
21.9 ± 2.3
30.2 ± 1.8
29.3 ± 3.3
36.1 ± 6.4
27.2 ± 4.3
23.2 ± 2.5
73.5 ± 1.0
7g
H
7h
H
7i
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-Me
4-F
7j
4-Me
3-Me
4-OMe
3-NO2
3-Cl
2-Cl
4-Cl
4-Br
H
7k
7l
7m
7n
7o
7p
12.3 ± 2.3
14.2 ± 0.4
13.2 ± 3.1
9.5 ± 3.0
7q
7r
7s
4-Me
3-Me
4-OMe
3-NO2
4-Br
/
4-F
7t
13.4 ± 0.5
17.5 ± 3.4
14.1 ± 2.2
9.6 ± 1.7
4-F
7u
4-F
7v
7w
4-F
4-F
7x
11.7 ± 0.3
47.7 ± 2.8
spirodiclofen
/
The acaricidal activity of compounds 1, 5a–c, 6a–c and 7a–x against the female
adults of Tetranychus cinnabarinus was tested by slide-dipping method [7,33].
Spirodiclofen was used as a positive control. As shown in Table 2, the mortality rate
(MR) at 72 h of compound 1 was 23.4%; whereas its lactam ring was opened, the
MRs at 72 h of its derivatives were increased. Especially three N-benzylmatrinic acids
(6a–c) showed the most potent acaricidal activity; for example, the MRs at 72 h of
compounds 6a–c were 52.2%, 61.0% and 49.8%, respectively. To compounds 5a–c
and 6a–c, generally, when R2 was the methyl group, the corresponding compounds 5b
and 6b exhibited more potent acaricidal activity than those containing other
substituents (e.g., 5b vs 5a and 5c; 6b vs 6a and 6c). To compounds 7a–x (except 7i),
in general, when R1 were the electron-donating groups such as 4-methyl, 3-methyl
10

and 4-methoxy, the corresponding compounds displayed more promising acaricidal
activity than those containing others (e.g, 7b–d vs 7a and 7e–h; 7k–m vs 7j and 7n–r;
7t–v vs 7s, 7w and 7x). To compounds 7b–d, 7k–m, and 7t–v, as mentioned above,
especially when R2 was the methyl group, the corresponding compounds 7k–m
exhibited more potent acaricidal activity than compounds 7b–d and 7t–v. Therefore,
it demonstrated that when R1 were the electron-donating groups, and R2 was the
methyl group, the corresponding compounds could show potent acaricidal activity.
This results were different with those of 3,19-diarylarbonyloxy andrographolides (the
derivatives containing the electron-withdrawing groups on the phenyl showed potent
acaricidal activity) [34].
4. Conclusion
In summary, a series of matrinic amide derivatives containing 1,3,4-thiadiazole
fragment (7a–x) were prepared, and evaluated for their pesticidal activities against
Mythimna separata and Tetranychus cinnabarinus. Among all derivatives, compound
7w exhibited the most potent insecticidal activity; compounds 7k–m showed
promising acaricidal activity. It demonstrated that R1 as a nitro group and R2 as a
fluorine atom, were important for the insecticidal activity; R1 as the electron-donating
groups and R2 as the methyl group, were necessary for the acaricidal activity.
Furthermore, three intermediates 6a–c displayed the most potent acaricidal activity.
These will pave the way for further structural modifications of matrine as potentially
botanical acaricidal and insecticidal agents in crop protection.
Conflicts of interest
11

The authors declare no competing financial interest.
Acknowledgements
The present research was partly supported by Key R&D Program of Shaanxi
Province (No. 2018NY-153), and Beijing Key Laboratory of Agricultural
Product Detection and Control for Spoilage Organisms and Pesticides,
Beijing University of Agriculture (No. 1086016009).
Appendix A. Supplementary data
Supplementary data (spectral data, and the protocol used for insecticidal and
acaricidal studies) associated with this article can be found, in the online version.
References
[1] X.F. Jiang, L. Zhang, H.X. Yang, T. W. Sappington, Y. X. Cheng, L. Z. Luo, Sci.
Rep. 6 (2016) 26873.
[2] Z.Q. Sun, M. Lv, X. Yu, H. Xu, ACS Sust. Chem. Eng. 5 (2017) 3945.
[3] L.J. Guillette Jr., T. Iguchi, Science 337 (2012) 1614.
[4] L. Lin, N. Mulholland, Q.Y. Wu, D. Beattie, S.W. Huang, D. Irwin, J. Clough, Y.C.
Gu, G.F. Yang, J. Agric. Food Chem. 60 (2012) 4480.
[5] F.E. Dayan, C.L. Cantrell, S.O. Duke, Bioorg. Med. Chem. 17 (2009) 4022.
[6] R. Sharma, L. Yadav, J. Lal, P.K. Jaiswal, M. Mathur, A.K. Swami, S. Chaudhary,
Bioorg. Med. Chem. Lett. 27 (2017) 4393.
[7] X.B. Huang, B.C. Zhang, H. Xu, Bioorg. Med. Chem. Lett. 27 (2017) 4336.
[8] Z.H. Gao, P.T. Yuan , D.H. Wang , Z.P. Xu, Z. Li, X.S. Shao, Bioorg. Med. Chem.
Lett. 27 (2017) 2528.
12

[9] T. Drobnjakovic, D. Marcic, M. Prijovic, P. Peric, S. Milenkovic, J. Boskovic,
Biocontrol Sci. Technol. 28 (2018) 1.
[10] S. Roy, G. Handique, F.R. Bora, A.J. Rahman, Environ. Biol. 39 (2018) 1.
[11] R. Yang, X. Huang, Z. Che, Y. Zhang, H. Xu, Ind. Crop Prod. 107 (2017) 45.
[12] L.A. Mendes, G.F. Martins, W.R. Valbon, T.D. de Souza, L. Menini, A. Ferreira,
M.F. da Silva Ferreira, Ind. Crop Prod. 108 (2017) 684.
[13] J. Huang, H. Xu, Curr. Top. Med. Chem. 16 (2016) 3365.
[14] Y. Liu, Y. Xu, W.D. Ji, X.Y. Li, B. Sun, Q.G. Gao, C.Q. Su, Tumor Biol. 35
(2014) 5111.
[15] L.M. Gao, Y.X. Han, Y.P. Wang, Y.H. Li, Y.Q. Shan, X. Li, Z.G. Peng, C.W.
Bi, T.A. Zhang, N.N. Du, J. Med. Chem. 54 (2011) 869.
[16] L.S. Wang, Y.J. You, S.Q. Wang, X. Liu, B.M. Liu, J.N. Wang, X. Lin, M.S.
Chen, G. Liang, H. Yang, Bioorg. Med. Chem. Lett. 22 (2012) 4100.
[17] O.Z. Zanardi, L.D. Ribeiro, T.F. Ansante, M.S. Santos, G.P. Bordini, P.T.
Yamamoto, J.D. Vendramim, Crop Prot. 67 (2015) 160.
[18] M.R. Mahmoud, M.M. El-Shahawi, F.S. Abu El-Azm, M. Abdeen, J. Heter.
Chem. 54 (2017) 2352.
[19] S.M. Gomha, N.A. Kheder, M.R. Abdelaziz, Y.N. Mabkhot, A.M. Alhajoj,
Chem. Cent. J. 11 (2017) 25.
[20] H. Dai, G. Li, J. Chen, Y.J. Shi, S.S. Ge, C.G. Fan, H.B. He, Bioorg. Med.
Chem. Lett. 26 (2016) 3818.
[21] G. Seelolla, V. Ponneri, J. Heter. Chem. 53 (2016) 929.
13

[22] T.T. Liu, Y.C. Wan, H. Fang, Chin. J. Org. Chem. 36 (2016) 417.
[23] M.S. Sallam, M.A. El-Hashash, D.B. Guirguis, Med. Chem. Res. 25 (2016)
369.
[24] J. Ramprasad, N. Nayak, U. Dalimba, P. Yogeeswari, D. Sriram,
MedChemComm 7 (2016) 338.
[25] J. Ramprasad, N. Nayak, U. Dalimba, P. Yogeeswari, D. Sriram, Bioorg.
Med. Chem. Lett. 25 (2015) 4169.
[26] J.L. Huang, M. Lv, H. Xu RSC Adv. 7 (2017) 15997.
[27] X. Yu, Z. Che, H. Xu, Chem. Eur. J. 23 (2017) 4467.
[28] Y.Y. Zhang, H. Xu, RSC Adv. 7 (2017) 35191.
[29] J.L. Huang, M. Xu, S.C. Li, J. He, H. Xu, Bioorg. Med. Chem. Lett. 27 (2017)
511.
[30] C.W. Bi, C.X. Zhang, Y.H. Li, S. Tang, H.B. Deng, W.L. Zhao, Z. Wang, R.G.
Shao, D.Q. Song, Eur. J. Med. Chem. 81 (2014) 95.
[31] L.Q. He, J. Liu, D.K. Yin, Y.H. Zhang, X.S. Wang, Chin. Chem. Lett. 21 (2010)
381.
[32] Z.P. Che, X. Yu, X.Y. Zhi, L.L. Fan, H. Xu, J. Agric. Food Chem. 61 (2013)
8148.
[33] K.M. Chang, C.O. Knowles, J. Agric. Food Chem. 25 (1977) 493.
[34] X.B. Huang, B.C. Zhang, H. Xu, Bioorg. Med. Chem. Lett. 28 (2018) 360.
14

Graphic abstract
Synthesis of matrinic amide derivatives containing 1,3,4-thiadiazole
scaffold as insecticidal/acaricidal agents
Min Lv, Guangci Liu, Minghong Jia, and Hui Xu*
15

Research highlights
► A series of matrinic amides containing 1,3,4-thiadiazole scaffold were prepared.
► Some compounds potent insecticidal and acaricidal activities.► Their
structure-activity relationships were observed.
16