Synthesis of sulfonate derivatives of maltol and their biological activity against Phytophthora capsici and Bursaphelenchus xylophilus in vitro

Article abstract of DOI:10.1080/10286020.2019.1608958

Sixteen sulfonate derivatives of maltol were synthesized and screened in vitro for their anti-oomycete and nematicidal activity against Phytophthora capsici and Bursaphelenchus xylophilus, respectively. Among all the compounds, 3e, 3m, and 3p exhibited th

Full text of DOI:10.1080/10286020.2019.1608958

Journal of Asian Natural Products Research
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Synthesis of sulfonate derivatives of maltol and
their biological activity against Phytophthora
capsici and Bursaphelenchus xylophilus in vitro
Yue-E Tian, Di Sun, Jin-Ming Yang, Zhi-Ping Che, Sheng-Ming Liu, Xiao-Min
Lin, Jia Jiang & Gen-Qiang Chen
To cite this article: Yue-E Tian, Di Sun, Jin-Ming Yang, Zhi-Ping Che, Sheng-Ming Liu, Xiao-Min
Lin, Jia Jiang & Gen-Qiang Chen (2019): Synthesis of sulfonate derivatives of maltol and their
biological activity against Phytophthoraꢀcapsici and Bursaphelenchusꢀxylophilusꢀinꢀvitro, Journal of
Asian Natural Products Research, DOI: 10.1080/10286020.2019.1608958
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JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
https://doi.org/10.1080/10286020.2019.1608958
Synthesis of sulfonate derivatives of maltol and their
biological activity against Phytophthora capsici and
Bursaphelenchus xylophilus in vitro
Yue-E Tian, Di Sun, Jin-Ming Yang, Zhi-Ping Che, Sheng-Ming Liu, Xiao-Min Lin,
Jia Jiang and Gen-Qiang Chen
Laboratory of Pharmaceutical Design and Synthesis, Department of Plant Protection, College of
Forestry, Henan University of Science and Technology, Luoyang 471003, China
ABSTRACT
ARTICLE HISTORY
Received 28 February 2019
Accepted 11 April 2019
Sixteen sulfonate derivatives of maltol were synthesized and
screened in vitro for their anti-oomycete and nematicidal activity
against Phytophthora capsici and Bursaphelenchus xylophilus,
respectively. Among all the compounds, 3e, 3m, and 3p exhibited
the most promising and pronounced anti-oomycete activity
against P. capsici than zoxamide, and the EC50 values of 25.42,
18.44, 23.69, and 27.99 mg/L, respectively; compounds 3e, 3m,
3n, and 3p exhibited potent nematicidal activity with LC50 values
ranging from 1 to 2 mg/L, especially 3m and 3n showed the best
promising and pronounced nematicidal activity, with LC50 values
of 1.1762 and 1.2384 mg/L, respectively.
KEYWORDS
Maltol; sulfonate;
semisynthesis;
anti-oomycete activity;
nematicidal activity
1. Introduction
The oomycete Phytophthora capsici, is a virulent, hemibiotrophic pathogen of vege-
table crops, inflicting significant losses worldwide [1–3]. Its main hosts are pepper
and cucurbits. The pathogen P. capsici has shown remarkable adaptation to
CONTACT Zhi-Ping Che
zhipingche@163.com
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

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Y.-E. TIAN ET AL.
Figure 1. Structures of aminoguanidine derivatives of N-arylsulfonyl-3-acylindoles (I) and N-arylsulfonyl-
3-acylindole arylcarbonyl hydrazine derivatives (II).
fungicides and new hosts [1–5]. Due to the lack of the resistant germplasm resour-
ces, chemical controlling is still the main way to reduce the incidence of P. capsici
on main hosts though resistance is an inevitable result of evolution [6–8]. However,
the oomycete P. capsici, which are hard to control, easily infect many crops, there-
fore development of new compounds that effectively inhibit those agricultural dis-
eases is still highly desirable.
Pine wood nematode (Bursaphelenchus xylophilus), is the cause of pine wilt disease,
which has been devastating forests worldwide [9]. Moreover, at present there are only
a few commercial nematicides left in use, and their repeated applications over the
years have led to the development of resistance [10]. To prevent pine wilt disease and
overcome the problems of resistance development and environmental pollution,
therefore, the research and development of efficacious nematicidal agents has received
much attention internationally in recent years [11].
Plant secondary metabolites play an important role in novel pesticide discovery for
their unique sources and potential target sites [12–16]. Maltol (1, 3-hydroxy-2-
methyl-4-pyrone, Scheme 1), a commercial natural metabolite, is primarily extracted
from germinated seeds of Hordeum vulgare L. and Triticum aestivum L. [17]. To the
best of our knowledge, compound 1 is an excellent candidate for the study of antifun-
gal activity [18], anticancer activity [19], antimycobacterial activity [20], antioxidant
activity [21], neuroprotective effect [22], and liver protection effect [23]. Moreover,
maltol is used extensively as a food preservative, flavor-enhancing agent, and also in
pharmaceutical and cosmetic formulations. More recently, we have investigated the
antifungal activities against Botrytis cinerea and Fusarium oxysporum of compound
containing hydroxyl of maltol [18]. In the meantime, the sulfonyl group introduced
at the skeletons of different natural products was necessary for obtaining the potent
compounds [11, 14, 24]. For example, aminoguanidine derivatives of N-arylsulfonyl-
3-acylindoles (I, Figure 1) exhibited the promising and pronounced antifungal activity
[24]; and N-arylsulfonyl-3-acylindole arylcarbonyl hydrazine derivatives (II, Figure 1)
showed significant nematicidal activity [11]. Inspired by the above-mentioned inter-
esting results, and the aim in our continuing endeavor to find more active natural

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
3
Scheme 1. The synthetic route of sulfonate derivatives of maltol (3a–p).
product-based antifungal hits [25], we herein designed and synthesized of three-sub-
stituted sulfonate derivatives of maltol, and first report the results of the antifungal
activity of 16 sulfonate derivatives of maltol against P. capsici and B. xylophilus in
vitro, respectively. Additionally, their structure–activity relationship (SAR) studies
were also described.
2. Results and discussion
2.1. Chemistry
As depicted in Scheme 1, maltol (1) reacted with 1.2 equiv. of ethanesulfonyl chlor-
ide/arylsulfonyl chloride (2a–p) in the presence of 1.5 equiv. of triethylamine to
afford 3-substituted sulfonate derivatives of maltol (3a–p) in relatively good yields.
2.2. Antioomycete activity
Sixteen sulfonate derivatives of maltol (3a–p) were screened in vitro for their antioo-
mycete activities against P. capsici [6]. Zoxamide, a commercially available agricul-
tural fungicide, was used as a positive control. And the inhibitory effects showed an
obviously dose-dependent manner that with the concentration of compound
increased, the colony diameter decreased.
As shown in Table 1, among all of the title derivatives, compounds 3e, 3m, and 3p
exhibited the most promising and pronounced anti-oomycete activity against P. cap-
sici than zoxamide. The EC50 values of 3e, 3m, 3p and zoxamide against P. capsici
were 25.42, 18.44, 23.69, and 27.99 mg/L, respectively. Generally, the introduction of
different substitutions at the hydroxyl position of maltol has remarkable effect on
antioomycete activity.
Through a comparative study on the relationship between the chemical structures
and antioomycete activity of 3a–p (SAR), some interesting results were found as fol-
lows: (1) The introduction of 4-tert-butylphenylsulfonyl at the hydroxyl position of
maltol could lead to more potent compound than possessing tosyl group, 4-methoxy-
phenylsulfonyl group and phenylsulfonyl group (3e versus 3c, 3d, and 3b). For
example, the EC50 values of 3e, 3c, 3d, and 3b against P. capsici were 25.42, 115.39,
151.88, and 196.69 mg/L, respectively, that is, the EC50 values of 3b was close to eight

4
Y.-E. TIAN ET AL.
Table 1. Anti-oomycete and nematicidal activities of compounds 3a–p against P. capsici and B.
xylophilus, respectively.
P. capsici
EC50 (mg/L)
B. xylophilus
LC50 (mg/L)
Compounds
R
Maltol
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
89.56
126.33
196.69
115.39
151.88
25.42
73.62
102.56
91.61
70.18
82.20
148.15
92.59
18.44
20.2237
5.5102
2.3956
5.5709
6.7881
1.5902
3.3387
4.0221
10.2235
12.3741
5.7106
2.3341
8.9812
1.1762
1.2384
3.8751
1.5624
Et
Ph
(p-Me)Ph
(p-OMe)Ph
(p-tert-butyl)Ph
(2,4,6-trimethyl)Ph
(2,4,6-triisopropyl)Ph
(p-F)Ph
(p-Br)Ph
(o-NO2)Ph
(m-NO2)Ph
(p-NO2)Ph
(p-Cl, m-NO2)Ph
2-thienyl
1-naphthyl
8-quinolyl
119.05
83.33
23.69
3p
Zoxamide
Emamectin benzoate
27.99
0.5603
times of that of 3e. Similarly, comparing the EC50 value of R ¼ 2,4,6-trimethylphenyl
derivative, it exhibited more potent anti-oomycete activity than R¼ 2,4,6-triisopropyl-
phenyl derivative. (2) Interestingly, we found that the introduction of nitrophenylsul-
fonyl at the hydroxyl position of maltol, and the nitro group at different position of
the benzene ring, could lead to derivatives with different antioomycete activity. For
example, the EC50 values of 3j, 3l, and 3k against P. capsici were 82.20, 92.59, and
148.15mg/L, respectively. In addition, the introduction of 4-bromophenylsulfonyl to
the hydroxyl position of maltol could lead to more potent compound than possessing
4-fluorophenylsulfonyl group (e.g. 70.18mg/L for 3i and 91.61 mg/L for 3h). It is note-
worthy that the introduction of 4-chloro-3-nitrophenylsulfonyl as a two-electron-with-
drawing substituent (such as NO2 and Cl) could result in more potent compound 3m
relative to those containing phenylsulfonyl as a one-electron-withdrawing substituent
(e.g. 3h-l). For example, the EC50 values of 3h–m against P. capsici were 91.61, 70.18,
82.20, 148.15, 92.59, and 18.44mg/L, respectively. (3) As compared with 2-thiophene-
sulfonyl and 1-naphthalensulyonyl derivatives, 8-quinolinesulfonyl derivative exhibited
more potent anti-oomycete activity (3n and 3o versus 3p). For example, the EC50 val-
ues of 3n–p against P. capsici were 119.05, 83.33, and 23.69 mg/L, respectively.
2.3. Nematicidal activity
Maltol, compounds 3a–p and emamectin benzoate (used as a positive control) were
screened in vitro for their nematicidal activities against B. xylophilus [11]. As outlined

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
5
in Table 1, among all of the derivatives, compounds 3e, 3m, 3n, and 3p exhibited
potent nematicidal activity with LC50 values ranging from 1 to 2 mg/L. Especially 3m
and 3n showed the best promising and pronounced nematicidal activity, with LC50
values of 1.1762 and 1.2384 mg/L, respectively.
Consequently, based upon the above investigation, when the sulfonyl moieties
were introduced on the 3-position of the maltol, the nematicidal activity of the corre-
sponding compounds were significantly increased (1 versus 3a–p). Finally, some
interesting results of the structure-activity relationships of 3a–p were also observed:
(1) The introduction of 4-tert-butylphenylsulfonyl at the hydroxyl position of maltol
could lead to more potent compound than possessing phenylsulfonyl group, tosyl
group, and 4-methoxyphenylsulfonyl group (3e versus 3b, 3c, and 3d). The LC50 val-
ues of 3b-e against B. xylophilus were 2.3956, 5.5709, 6.7881, and 1.5902 mg/L,
respectively. (2) It is interesting that the introduction of 4-chloro-3-nitrophenylsul-
fonyl as a two-electron-withdrawing substituent (such as NO2 and Cl) could result in
more potent compound 3m relative to those containing phenylsulfonyl as a one-elec-
tron-withdrawing substituent (e.g. 3h–l, the LC50 values ranging from 2.3341 to
12.3741 mg/L). On the other hand, we found that the introduction of nitrophenylsul-
fonyl at the hydroxyl position of maltol, and the nitro group at different position of
the benzene ring, could lead to derivatives with different nematicidal activity (3k ver-
sus 3j and 3l). (3) The introduction of the sulfonyl containing heterocyclic ring moi-
eties can significantly improve the nematicidal activity. As compared with 1-
naphthalensulyonyl derivative, 2-thiophenesulfonyl and 8-quinolinesulfonyl derivative
exhibited more potent nematicidal activity (3n and 3p versus 3o). For example, the
LC50 values of 3n-p against B. xylophilus were 1.2384, 3.8751, and 1.5624 mg/L,
respectively.
This suggested that a 4-chloro-3-nitrophenylsulfonyl group (two-electron-with-
drawing substituent) introduced at the hydroxyl position of maltol was necessary for
obtaining the most potent compound.
3. Experimental
3.1. General experimental procedures
Maltol, triethylamine, ethanesulfonyl chloride, and arylsulfonyl chloride were pur-
chased from Aladdin Chemistry Co., Ltd. (Shanghai, China). Ethyl acetate, dichloro-
methane and petroleum ether were purchased from Beichen Fangzheng Reagent
Factory (Tianjin, China). Analytical thin-layer chromatography (TLC) was performed
with silica gel plate using silica gel 60 GF254 (Qingdao Haiyang Chemical Co., Ltd.,
Shandong, China). Silica gel column chromatography was performed with silica gel
200–300 mesh (Qingdao Haiyang Chemical Co., Ltd., Shandong, China). Melting
points were taken on a X-6 microscopic melting point apparatus (Beijing Tech instru-
ment Co., Ltd., Beijing, China) and are uncorrected. Nuclear magnetic resonance
spectra (NMR) were recorded on a Bruker Avance DMX 400 MHz instrument
(Bruker Daltonik, Bremen, Germany) in CDCl3 (1H at 400 MHz) using TMS (tetra-
methylsilane) as the internal standard. Electrospray ion trap mass spectrometry (ESI-

6
Y.-E. TIAN ET AL.
TRAP-MS) was carried out with a Bruker ESI-TRAP Esquire 6000 plus mass spec-
trometry instrument (Bruker, Germany).
3.2. General procedure for the synthesis of sulfonate derivatives of
maltol (3a–p)
To a solution of maltol (1, 1.0 mmol) and ethanesulfonyl chloride/arylsulfonyl chlor-
ide (2, 1.2 mmol) in dry dichloromethane (DCM, 10 ml) at room temperature, a solu-
tion of triethylamine (Et3N) (1.5 mmol) in dry DCM (5 ml) was added dropwise for
10 min. When the reaction was completed by TLC analysis, the reaction mixture was
diluted with water (15 ml), and extracted with DCM (30 ml ꢀ 3). Subsequently, the
combined organic phase was washed by saturated aq. brine (30 ml), dried over anhyd-
rous Na2SO4, concentrated in vacuo, and purified by silica gel column chromatog-
raphy to obtain in 28–97% yields. The data for 3a–p are shown as follows.
3.2.1. Data for 3a
1
Yield ¼ 66%, Yellow oily liquid. H NMR (400 MHz, CDCl3) d: 7.70 (d, J ¼ 5.6 Hz,
1H), 6.42 (d, J ¼ 5.6 Hz, 1H), 3.72 (q, J ¼ 7.6 Hz, 2H), 2.46 (s, 3H), 1.60 (t, J ¼ 7.6 Hz,
3H). HRESIMS: m/z 219.0325 [M þ H]þ (calcd for C8H11O5S, 219.0322).
3.2.2. Data for 3b
1
Yield ¼ 78%, White solid, m.p. 106-107 ꢁC. H NMR (400 MHz, CDCl3) d: 8.10–8.13
(m, 2H), 7.68–7.72 (m, 1H), 7.66 (d, J ¼ 5.6 Hz, 1H), 7.56–7.60 (m, 2H), 6.34 (d,
J ¼ 5.6 Hz, 1H), 2.46 (s, 3H). HRESIMS: m/z 267.0321 [M þ H]þ (calcd for
C12H11O5S, 267.0322).
3.2.3. Data for 3c
1
Yield ¼ 31%, White solid, m.p. 96-97 ꢁC. H NMR (400 MHz, CDCl3) d: 7.96–7.99
(m, 2H), 7.65 (d, J ¼ 5.6 Hz, 1H), 7.35–7.38 (m, 2H), 6.34 (d, J ¼ 5.6 Hz, 1H), 2.46 (s,
6H). HRESIMS: m/z 281.0481 [M þ H]þ (calcd for C13H13O5S, 281.0478).
3.2.4. Data for 3d
1
Yield ¼ 97%, White solid, m.p. 87–88 ꢁC. H NMR (400 MHz, CDCl3) d: 8.02–8.05
(m, 2H), 7.65 (d, J ¼ 5.6 Hz, 1H), 7.00–7.04 (m, 2H), 6.34 (d, J ¼ 5.6 Hz, 1H), 3.89 (s,
3H), 2.47 (s, 3H). HRESIMS: m/z 297.0427 [M þ H]þ (calcd for
C13H13O6S, 297.0427).
3.2.5. Data for 3e
1
Yield ¼ 49%, White solid, m.p. 121–122 ꢁC. H NMR (400 MHz, CDCl3) d: 8.03–8.07
(m, 2H), 7.66 (d, J ¼ 5.6 Hz, 1H), 7.57–7.60 (m, 2H), 6.38 (d, J ¼ 5.6 Hz, 1H), 2.46 (s,
3H), 1.36 (s, 9H). HRESIMS: m/z 323.0949 [M þ H]þ (calcd for
C16H19O5S, 323.0948).

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
7
3.2.6. Data for 3f
1
Yield ¼ 28%, Yellow solid, m.p. 97-98 ꢁC. H NMR (400 MHz, CDCl3) d: 7.62 (d,
J ¼ 5.6 Hz, 1H), 6.99 (s, 2H), 6.29 (d, J ¼ 5.6 Hz, 1H), 2.66 (s, 6H), 2.45 (s, 3H), 2.32
(s, 3H). HRESIMS: m/z 309.0789 [M þ H]þ (calcd for C15H17O5S, 309.0791).
3.2.7. Data for 3g
1
Yield ¼ 59%, White solid, m.p. 82-83 ꢁC. H NMR (400 MHz, CDCl3) d: 7.62 (d,
J ¼ 5.6 Hz, 1H), 7.19 (s, 2H), 6.32 (d, J ¼ 5.6 Hz, 1H), 4.09–4.15 (m, 2H), 2.88–2.95
(m, 1H), 2.41 (s, 3H), 1.25–1.28 (m, 18H). HRESIMS: m/z 393.1731 [M þ H]þ (calcd
for C21H29O5S, 393.1730).
3.2.8. Data for 3h
1
Yield ¼ 85%, White solid, m.p. 146–147 ꢁC. H NMR (400 MHz, CDCl3) d: 8.12–8.17
(m, 2H), 7.67 (d, J ¼ 5.6 Hz, 1H), 7.22–7.28 (m, 2H), 6.35 (d, J ¼ 5.6 Hz, 1H), 2.50 (s,
3H). HRESIMS: m/z 285.0230 [M þ H]þ (calcd for C12H10FO5S, 285.0227).
3.2.9. Data for 3i
1
Yield ¼ 93%, White solid, m.p. 151–152 ꢁC. H NMR (400 MHz, CDCl3) d: 7.96–8.00
(m, 2H), 7.70-7.73 (m, 2H), 7.67 (d, J ¼ 5.6 Hz, 1H), 6.35 (d, J ¼ 5.6 Hz, 1H), 2.49 (s,
3H). HRESIMS: m/z 344.9429 [M þ H]þ (calcd for C12H10BrO5S, 344.9427).
3.2.10. Data for 3j
1
Yield ¼ 84%, Pale yellow solid, m.p. 148–149 ꢁC. H NMR (400 MHz, CDCl3) d: 8.27
(dd, J ¼ 8.0, 1.6 Hz, 1H), 7.90 (dd, J ¼ 7.6, 1.6 Hz, 1H), 7.67–7.85 (m, 2H), 7.68 (d,
J ¼ 5.6 Hz, 1H), 6.33 (d, J ¼ 5.6 Hz, 1H), 2.51 (s, 3H). HRESIMS: m/z 312.0175
[M þ H]þ (calcd for C12H10NO7S, 312.0172).
3.2.11. Data for 3k
1
Yield ¼ 56%, White solid, m.p. 105–106 ꢁC. H NMR (400 MHz, CDCl3) d: 8.94 (t,
J ¼ 2.0 Hz, 1H), 8.53–8.56 (m, 1H), 8.45–8.48 (m, 1H), 7.83 (t, J ¼ 8.0 Hz, 1H), 7.70
(d, J ¼ 5.6 Hz, 1H), 6.34 (d, J ¼ 5.6 Hz, 1H), 2.54 (s, 3H). HRESIMS: m/z 312.0173
[M þ H]þ (calcd for C12H10NO7S, 312.0172).
3.2.12. Data for 3l
1
Yield ¼ 49%, White solid, m.p. 132–133 ꢁC. H NMR (400 MHz, CDCl3) d: 8.39–8.43
(m, 2H), 8.29-8.32 (m, 2H), 7.70 (d, J ¼ 5.6 Hz, 1H), 6.35 (d, J ¼ 5.6 Hz, 1H), 2.53 (s,
3H). HRESIMS: m/z 312.0172 [M þ H]þ (calcd for C12H10NO7S, 312.0172).
3.2.13. Data for 3m
1
Yield ¼ 42%, White solid, m.p. 140–141 ꢁC. H NMR (400 MHz, CDCl3) d: 8.63 (d,
J ¼ 2.0 Hz, 1H), 8.28 (dd, J ¼ 8.4, 2.0 Hz, 1H), 7.79 (d, J ¼ 8.4 Hz, 1H), 7.70 (d,
J ¼ 5.6 Hz, 1H), 6.37 (d, J ¼ 5.6 Hz, 1H), 2.53 (s, 3H). HRESIMS: m/z 345.9785
[M þ H]þ (calcd for C12H9ClNO7S, 345.9783).

8
Y.-E. TIAN ET AL.
3.2.14. Data for 3n
1
Yield ¼ 29%, White solid, m.p. 94–95 ꢁC. H NMR (400 MHz, CDCl3) d: 7.93 (dd,
J ¼ 4.0, 1.2 Hz, 1H), 7.78 (dd, J ¼ 5.2, 1.6 Hz, 1H), 7.66 (d, J ¼ 5.6 Hz, 1H), 7.18 (dd,
J ¼ 5.2, 4.0 Hz, 1H), 6.36 (d, J ¼ 5.6 Hz, 1H), 2.45 (s, 3H). HRESIMS: m/z 272.9888
[M þ H]þ (calcd for C10H9O5S2, 272.9886).
3.2.15. Data for 3o
1
Yield ¼ 42%, White solid, m.p. 124-125 ꢁC. H NMR (400 MHz, CDCl3) d: 8.86–8.89
(m, 1H), 8.26 (dd, J ¼ 7.6, 1.6 Hz, 1H), 8.15–8.17 (m, 1H), 7.95-7.98 (m, 1H), 7.73-
7.77 (m, 1H), 7.61–7.65 (m, 1H), 7.60 (d, J ¼ 6.0 Hz, 1H), 7.57 (dd, J ¼ 8.4, 7.6 Hz,
1H), 6.26 (d, J ¼ 6.0 Hz, 1H), 2.39 (s, 3H). HRESIMS: m/z 317.0477 [M þ H]þ (calcd
for C16H13O5S, 317.0478).
3.2.16. Data for 3p
1
Yield ¼ 31%, White solid, m.p. 247–248 ꢁC. H NMR (400 MHz, CDCl3) d: 9.19 (dd,
J ¼ 4.4, 2.0 Hz, 1H), 8.50 (dd, J ¼ 7.6, 1.6 Hz, 1H), 8.30 (dd, J ¼ 8.4, 2.0 Hz, 1H), 8.16
(dd, J ¼ 8.4, 1.6 Hz, 1H), 7.67 (dd, J ¼ 8.4, 7.6 Hz, 1H), 7.61 (d, J ¼ 6.0 Hz, 1H), 7.58
(q, J ¼ 4.0 Hz, 1H), 6.19 (d, J ¼ 6.0 Hz, 1H), 2.57 (s, 3H). HRESIMS: m/z 318.0430
[M þ H]þ (calcd for C15H12NO5S, 318.0431).
3.3. Biological assay
3.3.1. Anti-oomycete activity of compounds 3a–p against P. capsici
Sixteen sulfonate derivatives of maltol (3a–p) were screened in vitro for their anti-
oomycete activity against P. capsici. Potato dextrose agar (PDA) medium was pre-
pared in the flasks and sterilized. Maltol, compounds 3a–p and zoxamide (used as a
positive control) were dissolved in acetone before mixing with PDA. The ranges of
maltol, compounds 3a–p and zoxamide concentrations for the assays were defined in
preliminary experiments, and the final concentrations in medium were 5, 25, 50, 75,
and 100 mg/L. Acetone without any compounds mixed with PDA was served as the
control. The medium was then poured into sterilized Petri dishes. Mycelial plugs (5-
mm diameter) were cut from the growing edge of a 7-day-old colony and then placed
on the PDA plates, and incubated at 28 ꢁC in the dark, respectively. Colony growth
rate (mm/7 days) was determined on PDA medium. Three plates were evaluated for
each compounds and an average colony diameter was calculated. The radial growths
of the colonies were measured and the data were statistically analyzed. Mean colony
diameter (minus the diameter of the plug) was measured for each treatment and
expressed as a percentage of growth inhibition. The median effective concentration
(EC50) of maltol, compounds 3a–p and zoxamide for P. capsici isolate was calculated
by linear regression of relative percentage of growth inhibition against logtransformed
samples concentration.
3.3.2. Nematicidal activity of compounds 3a–p against B. xylophilus
Sixteen sulfonate derivatives of maltol (3a–p) were screened in vitro for their nemati-
cidal activity against B. xylophilus. The ranges of maltol, compounds 3a–p and

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
9
emamectin benzoate (used as a positive control) concentrations for the assays were
defined in preliminary experiments. Acetone solutions of maltol, compounds 3a–p
and emamectin benzoate were first prepared at concentrations of 5, 10, 25, 50, and
100 mg/L, respectively. Then 10 ll of the above solutions was added to the aqueous
suspension (90 ll) containing approximate 1000 living nematodes (third-instar and
fourth-instar larvae of B. xylophilus) per milliliter. Acetone without any compounds
mixed was served as the control. Three replicates in each trial were made and kept at
28 ꢁC for 24 h. The activities of five concentrations of the tested compounds were
monitored under a microscope by recording the death rate of the tested nematodes.
Nematodes that did not move when prodded with a needle were considered to be
dead. The median lethal concentration (LC50) values of maltol, compounds 3a–p and
emamectin benzoate were calculated using the probit method.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was financially supported by the National Natural Science Foundation of China
(Grant No. U1604105) and the Natural Science Foundation of Henan Province (Grant No.
182300410043, 182300410016, 152300410082).
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