Research Article

Received: 26 January 2019 Revised: 29 March 2019 Accepted article published: 2 April 2019 Published online in Wiley Online Library:

(wileyonlinelibrary.com) DOI 10.1002/ps.5432

Synthesis and Fungicidal Activity of (E)-Methyl

2-(2-((1-cyano-2-hydrocarbylidenehydrazinyl)
methyl)phenyl)-2-(methoxyimino)acetates
Changqing Jia,a,b,† Xiaoyong Yuan,c,† Xuelian Liu,a Li Zhang,a Yumei Xiao,a
Bin Fu,a Jia-Qi Lia* and Zhaohai Qina*

Abstract
BACKGROUND: Strobilurin fungicides are some of the most potent and successful agrochemicals. However, continued use
of traditional strobilurins has led to the emergence of fungicide-resistant biotypes. Thus, a supply of new strobilurin fungicides
is highly valuable. In this study, a series of novel methoxyacrylate analogs containing a cyano-substituted hydrazine moiety
as the side chain was synthesized and evaluated for their anti-plant pathogenic activities.

RESULTS: Compounds 2-04, 2-05, 2-07 and 2-14 exhibited a relatively broad range of fungicidal activity. Compounds 2-04,
2-13 and 2-14 exhibited good fungicidal activity against Sclerotinia sclerotiorum with median effective concentrations (EC50 )
of 3.84, 3.50 and 3.80 𝛍g mL−1 , respectively. Most of these compounds showed excellent inhibition of spore germination in
Magnaporthe grisea at 25 𝛍g mL−1 . Moreover, in an in vivo test, compounds 2-02, 2-04, 2-07 and 2-13 exhibited potent fungicidal
activities against the tested plant diseases at 400 𝛍g mL−1 . Notably, compound 2-07 showed comparable or better activity than
the commercially positive controls, azoxystrobin and procloraz, against powdery mildew of cucumber and rice blast fungus in
the field trails at the same application dosages.

CONCLUSON: This study indicated that methoxyacrylate analogs containing a cyano-substituted hydrazone side chain can serve
as potential fungicidal candidates for crop protection.
© 2019 Society of Chemical Industry

Supporting information may be found in the online version of this article.

Keywords: Strobilurin fungicides; cyano-substituted hydrazine side chain; fungicidal activity; structure–activity relationships (SAR)

1 INTRODUCTION alkene (MOAs)15 and oxime (trifloxystrobin).16 In the view of

Strobilurin fungicides are some of the most potent and successful the structure of 2-07, the cyano-substituted hydrazone skeleton
agrochemicals of recent decades1 owing to their low toxicity and served as side chain; this has seldom been investigated in strobil-
high efficiency. They were valued at $3.743 billion and made urin fungicides.17 Surprisingly, compound 2-07 showed excellent
up nearly 22.9% of all fungicides in 2014.2 However, long-term fungicidal activity against Phytophthora infestans, Botryosphaeria
use of conventional strobilurins results in fungicide resistance.3 dothidea, Botrytis cinerea and several other plant pathogenic fungi.
Therefore, the development of novel strobilurin fungicides is of In this work, we modified this skeleton using 2-07 as the lead
importance to agrochemistry. compound to obtain mimics of compound (2) which were further
Recently, more and more insecticides targeting respiratory chain evaluated for their fungicidal activities (Fig. 1). Structure–activity
complexes have been developed, for example tebufenpyrad,4
fenpyroximate,5 cyflumetofen6 and fluacrypyrim.7 Based on simi-
∗
larities in their biological activity 8,9 and the principle of combining Correspondence to: Z Qin or J-Q Li, College of Science, China Agricultural
University, Beijing 100193, China.
active substructures,10,11 we reported the synthesis of a class of
E-mail: [email protected] (Qin); [email protected] (Li)
novel compounds that bore structural characteristics of both stro-
bilurin and N′ -nitrohydrazinecarboximidamide. These compounds † Contributed equally
exhibited excellent insecticidal and fungicidal activities.12 During
a Department of Applied Chemistry, College of Science, China Agricultural Uni-
the preparation of one of these bioactive molecules (1), com- versity, Beijing, China
pound 2-07 was obtained as a main byproduct. Many examples
have demonstrated that modification of the spacer side chain b National Engineering Research Center, Tongren Polytechnic College, Guizhou,
China
of strobilurins is an effective way to obtain new analogs with
high activities. Various frameworks have been introduced includ- c National Navel Orange Engineering Research Center, Gannan Normal Univer-
ing aryl ether (azoxystrobin),13 benzyl ether (kresoxim-methyl),14 sity, Ganzhou, China

Pest Manag Sci (2019) www.soci.org © 2019 Society of Chemical Industry

 www.soci.org C Jia et al.

Figure 1. Design approach to novel target molecules.

relationship (SAR) studies were performed extensively on all the resolved by direct methods with SHELXS-97. Hydrogen atoms were
derivatives to identify the key structural features responsible for observed and refined at a fixed value of their isotropic displace-
the fungicidal potency. ment parameter. Crystallographic data for the structure of com-
pound 2-07 have been deposited in the Cambridge Crystallo-
graphic Data Centre (deposition number CCDC 1580376).
2 MATERIALS AND METHODS
2.1 General 2.4 Bioactivity assay
1
H NMR and 13 C NMR spectra were obtained using a Bruker Avance 2.4.1 In vitro biological assay
DPX300 spectrometer in CDCl3 or DMSO-d6 solution using tetram- The fungicidal activity of the title compounds was tested in vitro
ethylsilane (TMS) as an internal standard. Chemical shift values (𝛿) against plant pathogens using the mycelia growth inhibition
are given in parts per million. High-resolution mass spectra (HRMS) method as described previously.18 Azoxystrobin, kresoxim-methyl
data were obtained on a Thermo Scientific LTQ Orbitrap Discovery and trifloxystrobin provided by Jiangsu Frey Chemicals Co. were
(Bremen, Germany) instrument. Melting points were determined used as controls. Mycelium growth inhibitory rate was measured
on a Cole-Parmer microscope melting point apparatus and and the activity against Sclerotinia. sclerotiorum was expressed
are uncorrected. Single crystal structure analysis was performed using EC50 (the concentration inhibiting mycelial growth by 50%)
using X-ray diffraction on a Bruker Smart APEX CCD diffractometer. values (95% fiducial limit; FL). The experiment was conducted
(E)-Methyl 2-(2-(bromomethyl)phenyl)-2-(methoxyimino)acetate twice with three replicates each time. The inhibition rate was
was a gift from Jiangsu Freychem Co (Zhenjiang, China). calculated as:
Relative inhibition ratio (%) = (C − T) ∕ (C − M) × 100%.
2.2 Synthetic procedure
2.2.1 General synthesis procedure for title compound 2. where C is the average diameter of mycelia in the control test, T is
A mixture of compound 4 (1 mmol)12 and cesium car- the average diameter of mycelia treated with the title compounds
bonate (15 mmol) in acetonitrile (100 mL) was placed in a and M is mycelial disk diameter. The fungicidal activities are listed
three-necked round-bottom flask (250 mL) and stirred for 30 min in Tables 1 and 2.
at room temperature. (E)-Methyl 2-(2-(bromomethyl)phenyl)-2- The inhibitory activity of the title compound towards spore ger-
(methoxyimino)acetate (18 mmol) was added and the resulting mination in Magnaporthe grisea and Botrytis cinerea was studied
mixture was refluxed for 10 h (Scheme 1). The reaction mixture in accordance with a reported method.18 The percentage of spore
was then cooled to room temperature, inorganic salt was filtered germination inhibition was calculated from mean values as
off and the filtrate was concentrated under vacuum. The residue
Inhibitory rate (%) = (A − B) ∕A × 100%.
was purified by chromatography on silica gel with petroleum
ether/ethyl acetate (5:1 v/v) as the eluent to give the desired where A is the percentage of germinated spores in the control and
product. B is the percentage of germinated spores in the sample. The results
are shown in Table 3.
2.3 Crystal structure determination for compound 2-07
Compound 2-07 was recrystallized by slow evaporation from 2.4.2 In vivo antifungal activity
a mixture of ethanol/ethyl acetate (1:3 v/v) to afford crystals The in vivo fungicidal activities of the title compounds against
suitable for X-ray diffraction analysis. Colorless pieces of 2-07 four plant pathogens were evaluated using a pot experiment,
were mounted on a quartz fiber. Cell dimensions and intensities as reported previously.19 Efficacy was expressed as the mean of
were measured using a Bruker Smart APEX CCD diffractometer values obtained in four independent experiments and the results
with graphite monochromated MoKa radiation. The structure was are shown in Table 4.

wileyonlinelibrary.com/journal/ps © 2019 Society of Chemical Industry Pest Manag Sci (2019)

Fungicidal activity of methoxyacrylates with cyano-substituted hydrazine www.soci.org

Scheme 1. Preparation of the title compounds.

Table 1. In vitro fungicidal activity against the phytopathogensa

Mycelium growth inhibitory rate (%) at 50 μg mL−1

Compound RS (rice) RS (cotton) SS BC PI BD PC PA CL

2-01 12.78 22.89 79.92 59.02 21.36 21.57 12.04 13.11 18.58
2-02 57.05 46.39 85.77 51.22 25.73 30.88 26.18 40.78 54.10
2-03 49.12 36.75 67.36 41.95 27.67 37.75 5.24 40.78 44.26
2-04 61.67 52.41 96.23 49.27 62.62 54.41 32.46 57.28 70.49
2-05 65.20 56.02 92.47 61.95 49.03 51.96 17.80 56.80 68.31
2-06 59.03 33.13 40.59 36.59 21.36 51.96 7.85 32.52 31.69
2-07 70.93 60.84 94.14 59.51 72.82 60.29 25.39 52.91 71.04
2-08 54.81 32.53 70.15 55.79 26.53 73.53 27.27 39.39 56.44
2-09 57.27 27.71 90.38 22.93 28.64 51.47 14.14 40.78 34.43
2-10 1.32 23.49 42.26 17.56 3.88 13.24 10.47 13.11 8.20
2-11 63.66 62.05 69.04 46.34 50.00 58.82 13.09 49.03 61.20
2-12 53.30 40.36 52.30 62.44 21.84 52.94 8.38 48.54 49.73
2-13 47.14 42.77 82.01 75.12 38.35 65.20 69.11 46.12 59.56
2-14 66.08 45.78 88.70 84.39 44.17 59.31 72.25 55.34 71.04
2-15 59.91 54.22 91.21 38.54 58.74 54.41 7.33 45.63 59.02
2-16 53.30 53.01 67.36 76.10 25.73 72.06 75.92 46.12 50.27
2-17 50.48 42.77 90.05 58.42 35.20 16.47 25.45 47.88 64.36
2-18 29.96 45.78 46.86 27.80 18.45 27.94 16.75 31.55 35.52
2-19 33.04 41.57 73.01 25.37 15.53 15.69 −0.52 18.93 27.87
2-20 63.38 31.55 58.61 40.01 42.00 57.52 30.91 45.51 26.48
5 63.44 49.76 44.35 35.61 61.65 39.71 10.99 32.04 47.54
6 64.77 35.70 98.31 76.67 62.00 62.75 50.00 53.85 27.10
Trifloxystrobin 74.89 66.27 100.00 89.27 62.14 72.06 77.49 64.08 69.40
Azoxystrobin 81.50 76.51 97.49 92.20 56.31 80.88 90.58 56.31 60.66
a Values are the mean of three replicates.
BC, Botrytis cinerea; BD, Botryosphaeria dothidea; CL, Colletotrichum lagenarium (Pass.); PA, Pythium aphanidermatum; PC, Phytophthora capsici; PI,
Phytophthora infestans; RS(rice), Rhizoctonia solani (rice); RS(cotton), Rhizoctonia solani (cotton); SS, Sclerotinia sclerotiorum; Ell. et Halst.

2.4.3 Field trials azoxystrobin used as the control was 337.5 g ai/ha (azoxystrobin
The fungicidal activity of 2-07 was evaluated in the field. Its 25% suspension concentrate; SC). Treatment was undertaken
efficacy against powdery mildew of cucumbers caused by three times every 7 days. The incidence of powdery mildew
Sphaerotheca fuliginea was conducted in Huaiyuan county, Tian- was surveyed 14 days after the third spraying. The trial against
jin, China. The application rate was 112.5, 225.0 and 337.5 g ai/ha Magnaporthe grisea (rice blast) was performed in Wuchang and
(2-07 10% emulsifiable concentrate; EC). The application rate of Fangzheng, Heilongjiang Province, China. The application rate

Pest Manag Sci (2019) © 2019 Society of Chemical Industry wileyonlinelibrary.com/journal/ps

 www.soci.org C Jia et al.

Table 2. In vitro fungicidal activity against Sclerotinia sclerotiorum

Compound EC50 (μg mL−1 ) 95% FL (μg mL−1 ) Compound EC50 (μg mL−1 ) 95% FL(μg mL−1 )

2-01 13.30 ± 0.34 9.80–16.35 2-13 3.51 ± 0.08 2.44–4.52

2-02 5.70 ± 0.19 4.44–6.96 2-14 3.80 ± 0.01 2.22–5.37
2-03 14.24 ± 0.24 9.78–18.71 2-15 3.94 ± 0.03 2.70–5.14
2-04 3.82 ± 0.17 2.53–5.11 2-16 13.07 ± 0.44 6.33–20.10
2-05 4.42 ± 0.01 2.87–5.95 2-17 5.64 ± 0.27 3.27–8.00
2-06 9.69 ± 0.11 4.33–14.93 2-18 26.33 ± 0.62 21.83–31.42
2-07 3.96 ± 0.10 2.92–4.85 2-19 20.12 ± 0.76 14.22–26.65
2-08 17.45 ± 0.43 12.76–22.42 2-20 11.52 ± 0.62 5.48–17.71
2-09 7.13 ± 0.26 2.81–11.72 6 7.75 ± 0.11 1.67–12.56
2-10 49.68 ± 2.36 35.52–78.19 Trifloxystrobin 0.08 ± 0.01 0.05–0.11
2-11 3.98 ± 0.11 3.00∼4.83 Azoxystrobin 0.27 ± 0.02 0.15–0.41
2-12 4.34 ± 0.14 2.95∼5.69

Table 3. The spore germination inhibition activities at 25 μg mL−1

Inhibitory rate (%) Inhibitory rate (%)

Compound MG BC Compound MG BC

2-01 100 0 2-13 100 50

2-02 100 0 2-14 100 0
2-03 80 0 2-15 100 0
2-04 100 0 2-16 100 50
2-05 100 0 2-17 100 0
2-06 100 0 2-18 50 0
2-07 100 0 2-19 100 0
2-08 100 0 2-20 50 0
2-09 100 0 Trifloxystrobin 100 0
2-10 0 0 Kresoxim-methyl 100 0
2-11 100 50
2-12 100 50

BC, Botrytis cinerea; MG, Magnaporthe grisea.

Table 4. In vivo fungicidal activity at 400 μg mL−1

Efficacy (%) Efficacy (%)

Compound PC BG PP CL Compound PC BG PP CL

2-01 0 75 85 0 2-13 75 30 100 50

2-02 75 50 85 100 2-14 0 0 55 60
2-03 30 40 0 0 2-15 0 0 20 0
2-04 0 80 98 100 2-16 0 0 75 0
2-05 0 80 98 0 2-17 0 0 30 0
2-06 0 35 60 0 2-18 40 0 50 0
2-07 30 75 90 100 2-19 0 70 70 0
2-08 0 70 80 0 2-20 0 0 30 0
2-09 0 75 95 60 Trifloxystrobin 95 100 100 80
2-10 0 75 0 0 Kresoxim-methyl 50 100 90 100
2-11 0 30 30 0
2-12 0 0 85 0

BG, Blumeria graminis f.sp.tritici; CL, Colletotrichum lagernarium; PC, Pseudoperonospora cubensis (Berk.et Curt.) Rostov.; PP, Puccinia polysora.

wileyonlinelibrary.com/journal/ps © 2019 Society of Chemical Industry Pest Manag Sci (2019)

Fungicidal activity of methoxyacrylates with cyano-substituted hydrazine www.soci.org

Table 5. Results of fungicidal activities of field trial against powdery mildew of cucumber

Significant differencec
Compounda Dosage (g ai/ha) Eb (%) 5% 1%

2-07 (10% EC) 112.5 65 c B

225.0 75 b A
337.5 78 a A
Azoxystrobin (25% SC) 337.5 75 b A
a EC, emulsifiable concentrate; SC, suspension concentrate.
b E, the average efficacy.
cLowercase letters (a–c) or uppercase letter (A–B) indicate no significant difference between the groups by one-way ANOVA with Tukey’s HSD test at
confidence level of P < 0.05 or P < 0.01, respectively.

Table 6. Results of fungicidal activities of field trial against rice blast

Eb (%) Ec (%)
Compounda Dosage (g ai/ha) Leaf blast Neck blast Leaf blast Neck blast

2-07 (10% EC) 180.0 80.56 78.56 –d 66.18

240.0 89.18 85.16 – 78.24
Procloraz (25% EC) 375.0 86.64 83.26 – 83.53
a EC, emulsifiable concentrate.
b E, the average efficacy obtained in Wuchang.
c E, the average efficacy obtained in Fangzheng.
d –, not determined.

was 180.0 and 240.0 g ai/ha (2-07 10% EC). The application rate of and 13.776 in the two different configurations. In addition, owing
procloraz used as the positive standard was 375.0 g ai/ha (proclo- to the electronic effect, the N(2)–C(10) and N(6)–C(30) bonds
raz 25% EC). The treatment was performed once at the rupturing are longer than a typical single C—N bond. The bond lengths
stage and boot stage, respectively. The incidence of leaf blast was of N(3)–C(7), N(7)–C(27) and N(4)–C(9), N(8)–C(29) bonds are
surveyed 7–10 days after spraying. The incidence of neck blast shorter than normal C N or C≡N bonds, respectively.
was surveyed at the ripeness stage. The disease index and efficacy
can be calculated as: 3.3 Structure–activity relationship analysis
∑ Fungicidal activity was investigated in vitro and in vivo, and the
Disease index = (N × n) × 100∕ (M × 9) . results are summarized in Tables 1–4. The results highlight some
important information. At a concentration of 50 μg mL−1 , most of
the title compounds showed excellent inhibition towards Sclero-
Efficacy (%) = (1 − PT∕CK) × 100%.
tinia sclerotiorum and Colletotrichum lagenarium (Pass.) Ell. et Halst.
This suggests that the two phytopathogens were more sensi-
where N is the number of diseased plants of each relative level, n
tive than others to this structural framework. Phytophthora capsici
is the relative level, M is the total number of diseased plants, PT is
was the most insensitive pathogen by comparison. Compounds
the disease index of the spraying area and CK is the disease index of
2-04, 2-05, 2-07 and 2-14 exhibited a broader fungicidal spec-
the blank control area before spraying. Results are listed in Tables 5
trum than other compounds. They showed inhibition activities
and 6.
comparable with control against Rhizoctonia solani (rice), Sclero-
tinia sclerotiorum, Phytophthora infestans, Pythium aphaniderma-
tum and Colletotrichum lagenarium (Pass.) Ell. et Halst. Interest-
3 RESULTS AND DISCUSSION
ingly, with the exception of 2-14, they showed much weaker
3.1 Synthesis
inhibition effects towards Phytophthora capsici compared with
The reaction of compound 4 with (E)-methyl 2-(2-(bromomethyl)
the control (Fig. 4). The poor activities of 2-01 and 2-10 towards
phenyl)-2-(methoxy-imino)acetate was complicated. In addition
nearly all of the tested phytopathogens indicated the necessity
to compound 2 and an analog of compound 1, compounds 5 and
of a substituted (hetero)aromatic ring at this position. Compared
7 were also isolated in most cases. Compound 6 was isolated as a
with 2-17, compound 6 exhibited far greater effectiveness against
major byproduct in the preparation of 2-17. The possible route for
the tested phytopathogens with the exception of Rhizoctonia
the formation of these compounds is given in Fig. 2.
solani (cotton) and Colletotrichum lagenarium (Pass.) Ell. et Halst
(Fig. 5). The broad fungicidal spectrum of compound 6 indicated
3.2 Crystal structure analysis that the dihydrazone skeleton as a linker might also be a good
Two different configurations of compound 2-07 are shown (Fig. 3, selection in methoxyacrylate fungicides. At 25 μg mL−1 , most of
right) which had slight differences in bond lengths and bond the title compounds showed excellent spore germination inhi-
angles. The dihedral angles of the two phenyl rings are ∼ 57.627 bition towards Magnaporthe grisea. This agreed with the energy

Pest Manag Sci (2019) © 2019 Society of Chemical Industry wileyonlinelibrary.com/journal/ps

 www.soci.org C Jia et al.

Figure 2. Plausible mechanism.

Figure 3. ORTEP drawing with thermal ellipsoids drawn at 30% probability for compound 2-07 and the packing representation.

wileyonlinelibrary.com/journal/ps © 2019 Society of Chemical Industry Pest Manag Sci (2019)

Fungicidal activity of methoxyacrylates with cyano-substituted hydrazine www.soci.org

120 2-04
100
2-05
80
2-07
60
2-14
40
20 trifloxystrobin

0 azoxystrobin
RS RS SS BC PI BD PC PA CL
(rice) (cotton)

Figure 4. Comparison of fungicidal activities of selected compounds with controls.

120 2 Bai YL, Global market analysis of strobilurin fungicide. J China Agrochem
2-17 6 3:61–67 (2016).
100 3 Zhao P, Yan QX, Li X and Zhang MH, Current status of resistance and
80 development of strobilurin fungicides. Agrochemicals 50:547–551
(2011).
60 4 Schuler F and Casida JE, The insecticide target in the PSST subunit of
40 complex I. Pest Manag Sci 57:932–940 (2001).
5 Motoba K, Suzuki T and Uchida M, Effect of a new acaricide, fenpy-
20 roximate, on energy metabolism and mitochondrial morphology in
0 adult female Tetranychus urticae (two-spotted spider mite). Pestic
RS RS SS BC PI BD PC PA CL Biochem Physiol 43:37–44 (1992).
(rice) (cotton) 6 Hayashi N, Sasama Y, Takahashi N and Ikemi N, Cyflumetofen, a
novel acaricide – its mode of action and selectivity. Pest Manag Sci
Figure 5. Comparison of fungicidal activities of compounds 2-17 and 6. 69:1080–1084 (2013).
7 Thibault L and Delome R, Acaricides in crop protection. Phytoma
586:38–41 (2005).
formation inhibition mechanism of methoxyacrylate fungicides. 8 Xie Y, Peng W, Ding F, Liu S-J, Ma H-J and Liu C-L, Quantitative
However, they were almost completely ineffective towards Botry- structure–activity relationship (QSAR) directed the discovery of
tis cinerea at this concentration. In an in vivo test, compounds 3-(pyridin-2-yl)benzenesulfonamide derivatives as novel herbicidal
agents. Pest Manag Sci 74:189–199 (2018).
2-02, 2-04, 2-07 and 2-13 exhibited potent activities against the
9 Tiikkainen P, Poso A and Kallioniemi O, Comparison of structure finger-
tested plant diseases, comparable with commercial fungicides. print and molecular interaction field based methods in explaining
Compound 2-07 exhibited comparable or better activities than biological similarity of small molecules in cell-based screens. J Com-
control plant virus inhibitors in field trials. put Aided Mol Des 23:227–239 (2009).
10 Guan A-Y, Liu C-L, Li M, Zhang H, Li Z-N and Li Z-M, Design, synthesis
and structure–activity relationship of novel coumarin derivatives.
Pest Manag Sci 64:674–655 (2011).
4 CONCLUSION 11 Wu J, Wang J, Hu DY, He M, Jin LH and Song BA, Synthesis and antifun-
In summary, we report the synthesis of a series of novel gal activity of novel pyrazolecarboxamide derivatives containing a
methoxyacrylate fungicidal compounds specialized with a hydrazone moiety. Chem Cent J 6:51 (2012).
cyano-substituted hydrazone side chain. The compounds exhib- 12 Yuan XY, Jia CQ, Ma YQ, Yang DY, Rui CH and Qin ZH, Synthesis, insecti-
cidal and fungicidal activities of methyl 2-(methoxyimino)-2-(2-((1-
ited excellent fungicidal activity against tested phytopathogens (N′ -nitrocarbamimidoyl)-2-hydrocarbylidenehydrazinyl)methyl)
both in vitro and in vivo. Preliminary results indicated that com- phenyl)acetates. RSC Adv 6:19916–19922 (2016).
pound 2-07 displayed field efficacy comparable with or better 13 Lamberth C, Agrochemical lead optimization by scaffold hopping. Pest
than those of commercial fungicides and suggested that this Manag Sci 74:282–292 (2018).
14 Bartlett DW, Clough JM, Godwin JR, Hall AA, Hamer M and
type of compound might be considered for use in plant diseases Parr-Dobrzanski B, The strobilurin fungicides. Pest Manag Sci
control. Meanwhile, the broad spectrum fungicidal activities of 58:649–662 (2002).
compound 6 also provided us a new clue in the design of novel 15 Jeschke P, Progress of modern agricultural chemistry and future
methoxyacrylate derivatives. prospects. Pest Manag Sci 72:433–455 (2016).
16 Xie Y-Q, Huang Y-B, Liu J-S, Ye L-Y, Che L-M, Tu S et al., Design, synthe-
sis and structure–activity relationship of novel oxime ether strobil-
urin derivatives containing substituted benzofurans. Pest Manag Sci
ACKNOWLEDGEMENTS 71:404–414 (2015).
This study was supported by grants from the National Key R&D 17 Grammenos W, Harreus A, Sauter H, Hellenheim B, Doetzer R, Ammer-
Program of China (2018YFD0200103). mann E et al., Imino-substituierte phenylderivate, ihre herstellung
und diese enthaltende fungizide. EP0499823A2 (1992).
18 Yan XJ, Qin WC, Sun LP, Qi SH, Yang DB, Qin ZH et al., Study of inhibitory
effects and action mechanism of the novel fungicide pyrimorph
SUPPORTING INFORMATION against Phytophthora capsici. J Agric Food Chem 58:2720–2725
Supporting information may be found in the online version of this (2010).
article. 19 Hostettmann K and Harborne JB, in Methods in Plant Biochemistry, Vol.
6, assays for bioactivity. ed. by Dey PM. Academic Press, London, pp.
33–46 (1991).
REFERENCES
1 Zakharychev VV and Martsynkevich AM, Strobilurin analogs in plant
protection. Agrokhimiya 36:64–74 (2013).

Pest Manag Sci (2019) © 2019 Society of Chemical Industry wileyonlinelibrary.com/journal/ps