Synthesis and fungicidal activity of aryl carbamic acid-5-aryl-2- furanmethyl ester

Article abstract of DOI:10.1021/jf9043277

Chitin, a major structural component of insect cuticle and fungus cell wall but absent in plants and vertebrates, is regarded as a safe and selective target for pest control agents. Chitin synthesis inhibitors (CSIs) have been well-known as insect growth regulators (IGRs) but rarely found as fungicides in agriculture. To find novel CSIs with good activity, benzoylphenylurea, a typical kind of CSIs, was chosen as the lead compound and 26 novel aryl carbamic acid-5-aryl-2-furanmethyl esters were designed by converting the urea linkages of benzoylphenylureas to carbamic acid esters and changing the aniline parts into furanmethyl groups. The title compounds were synthesized and their structures confirmed by IR, ¹H NMR, and elemental analysis. Preliminary insecticidal and fungicidal bioassays were carried out. The results indicated that the title compounds had no insecticidal effect on Culex pipiens pallens and Plutella xylostella Linnaeus, but most compounds exhibited good fungicidal activities against Corynespora cassiicola, Thanatephorus cucumeris, Botrytis cinerea, and Fusarium oxysporum. In particular, compounds V-4, V-6, V-7, and V-8 showed better activities against the four strains than those of the commercialized fungicides. The morphologic result suggested that compound V-21 had disturbed the cell wall formation of C. cassiicola. The results indicated that modification on the urea linkage of benzoylphenylurea was an effective way to discover new candidates for fungicides.

Full text of DOI:10.1021/jf9043277

J. Agric. Food Chem. 2010, 58, 3037–3042 3037
DOI:10.1021/jf9043277
Synthesis and Fungicidal Activity of Aryl Carbamic
Acid-5-aryl-2-furanmethyl Ester
#
Y
ING
L
I
,§ BAO-J
U
L
I
,# YUN
L
X
ING,*,§ HONG-JIAN
,§
M
IAO,§ YAN-XIA
SHI
,
AND
IN-LING
Y
ANG
*
§Department of Applied Chemistry, College of Science, Key Laboratory of Pesticide Chemistry and
Application, MOA, China Agricultural University, Beijing 100193, People’s Republic of China, and
#Institute of Vegetables and Flowers, Chinese Academy of Agricultural Sciences, Beijing 100081,
People’s Republic of China
Chitin, a major structural component of insect cuticle and fungus cell wall but absent in plants and
vertebrates, is regarded as a safe and selective target for pest control agents. Chitin synthesis
inhibitors (CSIs) have been well-known as insect growth regulators (IGRs) but rarely found as
fungicides in agriculture. To find novel CSIs with good activity, benzoylphenylurea, a typical kind of
CSIs, was chosen as the lead compound and 26 novel aryl carbamic acid-5-aryl-2-furanmethyl
esters were designed by converting the urea linkages of benzoylphenylureas to carbamic acid
esters and changing the aniline parts into furanmethyl groups. The title compounds were synthe-
1
sized and their structures confirmed by IR, H NMR, and elemental analysis. Preliminary insecticidal
and fungicidal bioassays were carried out. The results indicated that the title compounds had no
insecticidal effect on Culex pipiens pallens and Plutella xylostella Linnaeus, but most compounds
exhibited good fungicidal activities against Corynespora cassiicola, Thanatephorus cucumeris,
Botrytis cinerea, and Fusarium oxysporum. In particular, compounds V-4, V-6, V-7, and V-8 showed
better activities against the four strains than those of the commercialized fungicides. The morpho-
logic result suggested that compound V-21 had disturbed the cell wall formation of C. cassiicola.
The results indicated that modification on the urea linkage of benzoylphenylurea was an effective
way to discover new candidates for fungicides.
KEYWORDS: Chitin synthesis inhibitors; benzoylphenylureas; carbamic acid ester; synthesis; fungi-
cidal activity
INTRODUCTION
Chitin, the β-(1f4)-linked homopolymer of N-acetyl-
modifications on the benzoyl (X) and aniline (Z) parts led to
the discoveries of many commercial insecticides, such as difluben-
zuron, chlorfluazuron, teflubenzuron, bistrifluoron, and noviflu-
muron (9-13). However, modification on the urea linkage (Y)
was less considered, but some efforts on this part have been made.
For example, Grosscurt found that the compounds had good
insecticidal properties when the urea linkage was converted into
carbamoyl-2-pyrazolines (14). Chen reported that the substitu-
tion of the hydrogen on the nitrogen atom of urea linkage with
carbamylosulfenyl or formate could retain the insecticidal
activity (15-17).
In our previous work, the benzoyl (X) part was modified with a
furoyl group to get benzoylureas B (20), and the aniline (Z) part
was replaced with a furoyl group to obtain dibenzoylureas
C (18, 19). Their bioassay results indicated that some compounds
also had certain insecticidal activity. In the present work, an effort
of structure optimization was carried out, in which the urea linkage
was converted to carbamic acid ester by replacing NH with O,
whereas the aniline part was replaced with a furanmethyl group
(Scheme 1). Twenty-six novel aryl carbamic acid-5-aryl-2-furan-
methyl esters (V) were designed and synthesized for the purpose
of new pesticide discovery. Their insecticidal activities in vivo
and fungicidal activities in vitro were evaluated preliminarily.
D-glucos-
amine, is a major structural component of insect cuticles and
fungus cell walls but absent in plants and vertebrates. This
taxonomic difference provides the rationale for considering chitin
as a safe and selective target for pest control agents (1, 2). Chitin
synthesis inhibitors (CSIs), which can disrupt the formation of
chitin, will affect the normal growth and development of insects
and fungi but have no effect on vertebrates and plants. CSIs play
an important role in integrated pest management (IPM). There-
fore, to find new CSIs it is necessary to meet the requirement of
various pest managements in sustainable agriculture (3, 4).
Benzoylphenylureas (BPUs), first discovered in the 1970s, are a
typical kind of CSI (5, 6). BPUs have attracted considerable
attention for decades because of their unique mode of action
coupled with high activities on targeted pests and low toxicity
to nontarget organisms (5-17). Their general structures A consist
of three parts including the benzoyl (X), the urea linkage (Y),
and the aniline (Z) (9). During the past three decades, many
*Authors to whom correspondence should be addressed [telephone
86-10-62732223; fax 86-10-62732223; e-mail (Xin-Ling Yang) yangxl@
cau.edu.cn or (Yun Ling) lyun@cau.edu.cn].
© 2010 American Chemical Society
Published on Web 02/12/2010
pubs.acs.org/JAFC

3038 J. Agric. Food Chem., Vol. 58, No. 5, 2010
Scheme 1. Design Strategy for Target Compounds V
Li et al.
Furthermore, a morphological study on the cell wall formation of
Corynespora cassiicola was done primarily to identify whether the
formation of chitin had been disrupted or not.
All other title compounds were prepared according to the same
procedure as compound V-26. The data of their yields, melting points,
and elemental analyses are listed in Table 1 and the data of 1H NMR and
IR are listed in Table 2.
Biological Assays. Insecticidal Activity
MATERIALS AND METHODS
(a) Insecticidal Activity against Plutella xylostella Lin-
naeus. Insecticidal activities against P. xylostella Linnaeus were evalu-
ated using the immersion method (24). P. xylostella Linnaeus was
maintained in the Institute of Plant Protection, Chinese Academy of
Agricultural Science. Test solutions were made by dissolving the title
Instruments and Reagents. Melting points were measured on a Cole-
Parmer melting point apparatus, and the thermometer was uncorrected.
1H NMR spectra were obtained in deuterochloroform or hexadeuterodi-
methyl sulfoxide using a Bruker Advance DPX (300 MHz) (Switzerland)
with tetramethylsilane as internal standard. Elemental analysis was
performed on an ST-Carlo Erba Flash EA 1112 elemental analyzer by
the Analytical Center of the Institute of Chemistry, Chinese Academy of
Science. Infrared spectra (νmax in cm-1) were recorded on a Shimadzu
IR-435 apparatus. The solvents and reagents were mainly purchased from
the Beijing Chemical Reagents Co., People’s Republic of China.
Chemical Synthesis. General Procedure for the Synthesis of Com-
pounds 5-Aryl-2-furanmethanol (II). Compounds II were prepared from
compound I with NaBH4 as the reductant (21), and I was synthesized from
substituted aniline by Meerwein arylation reaction using the reported
procedure (22).
compounds in a mixture solvent of acetone and methanol (Vacetone
/
Vmethanol = 1:1), adding a little 0.1% Tween-80 as the emulsifier, and
then diluting to 600 mg L-1 with water. The insects were raised at 27 (
1 °C, with a 12:12 h (light/dark) photoperiod and 80% relative humidity.
The results were observed after 72 h and expressed by death percentage.
The mixture solvent of acetone and methanol was set as blank control, and
87% fipronil was set as insecticidal control. Three replicates were
performed.
(b) Larvicidal Activity against Mosquito (Culex pipiens
pallens). Larvicidal activities of the target compounds V against mos-
quitoes were evaluated by using the reported procedure (16). Compounds
V were dissolved in acetone and distilled water at a terminal concentration
of 2000 mg L-1. Then 20 fourth-instar mosquito larvae were put into
10 mL of the tested solution and raised for 8 days. The results were
expressed by death percentage. RH-5849 and acetone were set as insec-
ticidal and blank control. They were tested under the same condition as V.
Four replicates were performed.
General Procedure for the Synthesis of Substituted Benzoyl Isocyanate
(IV). Compounds IV were obtained through the reaction of corresponding
benzamides III and oxalyl dichloride according to the literature (23).
General Procedure for the Synthesis of the Target Compound V-26. Into
a solution of 5-(4-bromophenyl)-2-furanmethanol (1.5 g, 0.006 mol)
dissolved in 30 mL of purified toluene was added 2-chlorobenzoyl
isocyanate (1.29 g, 0.007 mol). The reaction mixture was stirred at room
temperature for 0.5 h. The solvent was filtered off. The solid was dried and
then recrystallized from the mixture solvent of petroleum ether and ethyl
acetate (Vpetroleum ether/Vethyl acetate = 2.5:1). A white solid (V-26, 184 g)
was obtained in 71.4% yield: mp 114-116 °C; 1H NMR (300 MHz)
δ 11.37 (s, 1H, NH), 7.61-7.68 (m, 4H, ArH-Fu), 7.36-7.50 (m, 4H,
ArH), 7.03 (d, J = 3.39 Hz, 1H, FuH), 6.69 (d, J = 3.39 Hz, 1H, FuH),
Fungicidal Activity. The preliminary fungicidal activities in vitro were
tested against four kinds of strains: Botrytis cinerea, Corynespora cassii-
cola, Fusarium oxysporum, and Thanatephorus cucumeris. All of the strains
were conserved in the Institute of Vegetable and Flowers, Chinese
Academy of Agricultural Science. Commercialized fungicides, 75% chloro-
thalonil WP, 3% jingangmycin AS, 40% pyrimethanil SC, and 70%
thiophanate-methyl WP were set as control for the above four strains,
respectively.
5.17 (s, 2H, CH2); IR, ν 3200, 1770, 1690, 1510, 1480, 1220, 1040 cm-1
.
The fungicidal activities of the title compounds V against above four
strains in vitro were evaluated using the mycelium growth rate test (25).
Anal. Calcd for C19H13BrClNO4: C, 52.50; H, 3.01; N, 3.22. Found: C,
52.46; H, 3.01; N, 3.35.

Article
J. Agric. Food Chem., Vol. 58, No. 5, 2010 3039
Table 1. Physical and Elemental Data of Compounds V
elemental analysis
compd
R1
R3
2-F
mp (°C)
yield (%)
C (calcd)
H (calcd)
N (calcd)
V-1
V-2
2,6-F2
2,6-F2
2,6-F2
2,6-F2
2,6-F2
2,6-F2
2,6-F2
2,6-F2
2,6-F2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2,6-Cl2
2-Cl
114-116
118-119
131-133
120-121
122-124
123-125
121-122
117-118
124-126
145-147
147-149
133-135
147-149
146-148
150-152
146-148
145-146
135-137
123-124
129-131
131-133
105-106
138-139
143-144
106-107
143-144
77.3
78.6
73.5
52.4
41.5
50.8
48.6
53.4
61.5
75.9
71.8
75.6
78.9
88.4
64.2
83.5
83.1
70.5
68.2
51.1
83.6
36.4
70.6
88.7
74.1
71.4
60.99 (60.81)
60.60 (60.81)
60.78 (60.81)
57.90 (58.02)
58.16 (58.25)
58.09 (58.25)
58.21 (58.25)
52.47 (52.32)
52.28 (52.32)
55.74 (55.90)
55.85 (55.90)
55.96 (55.90)
53.56 (53.54)
53.68 (53.74)
53.66 (53.74)
53.92 (53.74)
48.51 (48.65)
48.92 (48.65)
61.03 (61.06)
61.35 (61.06)
60.80 (61.06)
58.26 (58.48)
58.31 (58.48)
58.28 (58.48)
52.64 (52.50)
52.46 (52.50)
3.32 (3.22)
3.22 (3.22)
3.33 (3.22)
2.97 (2.82)
3.16 (3.09)
3.28 (3.09)
3.14 (3.09)
2.94 (2.77)
2.83 (2.77)
2.98 (2.96)
3.10 (2.96)
2.99 (2.96)
2.80 (2.60)
2.91 (2.85)
2.98 (2.85)
2.91 (2.85)
2.70 (2.58)
2.65 (2.58)
3.69 (3.51)
3.52 (3.51)
3.54 (3.51)
3.34 (3.36)
3.43 (3.36)
3.36 (3.36)
2.98 (3.01)
3.01 (3.01)
3.65 (3.73)
3.90 (3.73)
3.94 (3.73)
3.74 (3.56)
3.58 (3.58)
3.82 (3.58)
3.75 (3.58)
3.47 (3.21)
3.34 (3.21)
3.18 (3.43)
3.55 (3.43)
3.56 (3.43)
3.44 (3.29)
3.48 (3.30)
3.26 (3.30)
3.48 (3.30)
2.98 (2.99)
3.24 (2.99)
3.82 (3.75)
3.81 (3.75)
3.94 (3.75)
3.71 (3.59)
3.70 (3.59)
3.80 (3.59)
3.33 (3.22)
3.35 (3.22)
3-F
4-F
V-3
V-4
2,4-F2
2-Cl
3-Cl
4-Cl
2-Br
4-Br
2-F
V-5
V-6
V-7
V-8
V-9
V-10
V-11
V-12
V-13
V-14
V-15
V-16
V-17
V-18
V-19
V-20
V-21
V-22
V-23
V-24
V-25
V-26
3-F
4-F
2,4-F2
2-Cl
3-Cl
4-Cl
2-Br
4-Br
2-F
2-Cl
2-Cl
3-F
4-F
2-Cl
2-Cl
2-Cl
3-Cl
4-Cl
2-Br
4-Br
2-Cl
2-Cl
2-Cl
Both control fungicides and synthesized compounds were dissolved in
DMF at the concentration of 50 mg L-1. The culture media were obtained
by mixing the solution of compounds V in DMF with potato dextrose agar
(PDA), on which fungus cakes were placed. The blank test was made using
DMF. The culture had been stored in an incubator at 24 ( 0.5 °C for
2 days. Three replicates were performed. After the mycelia grew com-
pletely, the diameters of the mycelia were measured and the inhibitory
rates were calculated according to the formula
All of the structures of title compounds were confirmed by 1H
NMR, IR, and elemental analyses. In the IR spectra, the
compounds showed absorption bands around 3200 cm-1 origi-
nating from the N-H stretching vibration. The strong bands
around 1750 cm-1 could be assigned to the CdO stretching
vibration. The bands between 1690 and 1620 cm-1 were carbonyl
vibration of the secondary amide. Absorption bands around 1510
and 1480 cm-1 were attributed to the frame vibration of the
phenyl ring.
C -T
I ð%Þ ¼
ꢀ 100%
1
In the H NMR spectrum, one sharp peak in the range from
C
11.36 to 11.71 ppm was due to the presence of NH. The splits of
most compounds were normal except for the compounds with
fluorine substitution because of the coupling and splitting between
fluorine and hydrogen. The fluorine atom splits a hydrogen proton
into a doublet, which complicated the proton signal. Mostly, the
protons on phenyl rings were split into multiple peaks in the range
from 7.10 to 7.90 ppm and the protons on the furan ring were split
into a doublet in the range from 6.70 to 7.30 ppm. All of the CH2
appeared in a single peak around 5.20 ppm.
Biological Activity. Considering that the lead compounds B
and C had good insecticidal activities against dipterous and
lepidopterous insects, we chose C. pipiens pallens and P. xylostella
Linnaeus first to evaluate whether the designed compounds
retained the insecticidal activity. Unfortunately, as shown in
Tables 3 and 4, compounds V had no insecticidal effect on
C. pipiens pallens even at 2000 mg L-1 or on P. xylostella Linnaeus
at 600 mg L-1. It is well-known that the BPUs were discovered
dramatically when Wellinga from Philips-Duphar screened for
herbicides in the 1970s (5). Our title compounds, in which the urea
linkage was converted to carbamic acid ester by replacing NH with
O, might have other activity instead of insecticidal activity.
Filippini (27) and Fukumoto (28) reported that compounds
valiphenal and pyribencarb, which contain a carbamate moiety,
showed excellent fungicidal activities and safety to crops and
nontargeted organisms. Enlightened by the results from Filippini
and Fukumoto, we turned to study fungicidal activities of the title
in which I stands for the inhibition (%), C for the diameter of mycelia in
the blank control test (in mm), and T for the diameter of mycelia in the
presence of compounds V (in mm). The results are shown in Table 5.
Morphological Study on Cell Wall of Fungus. C. cassiicola was
taken as test fungus, V-21 was selected as test compound, and thiophanate
methyl (TM) was chosen as control fungicide in the morphological study.
V-21 and TM were dissolved in DMF and Tween-80 at the concentration
of 1000 mg L-1. The culture media were obtained by mixing the solution of
compound V-21 in DMF with PDA, on which fungus cakes were placed.
The blank test was made using DMF. The culture had been stored in an
incubator at 24 ( 0.5 °C. When the diameter of mycelia in the blank
control test grew to 2-3 cm, the culture media with mycelia were taken out
for stained preparation. The morphology of the cell wall of C. cassiicola
was observed using an optical microscope (26).
RESULTS AND DISCUSSION
Synthesis. The synthetic route of compounds V is shown in
Scheme 2, where the starting materials were substituted anilines
and benzoic acids. All of the target compounds were prepared by
the nucleophilic addition reaction of 5-substituted-phenyl-2-fur-
anmethanol with benzoyl isocyanate in the system without
moisture. The reaction occurred in toluene at room temperature
as soon as the benzoyl isocyanate was added into the solution
containing 5-aryl-2-furanmethanol. The reaction should be kept
at low temperature because the 5-aryl-2-furanmethanol easily
decomposes when the temperature is >80 °C.

3040 J. Agric. Food Chem., Vol. 58, No. 5, 2010
Li et al.

Article
J. Agric. Food Chem., Vol. 58, No. 5, 2010 3041
Scheme 2. General Synthetic Procedure for Target Compounds V
Table 3. Larvicidal Activity against Culex pipiens pallens at 2000 mg L-1
Table 5. Fungicidal Activities of Compounds V against Four Fungus Species
at 50 mg L-1
compd
mortality (%)
compd
mortality (%)
compd
mortality (%)
inhibitory rate(%)
V-1
V-2
V-3
V-4
V-5
V-6
V-7
V-8
V-9
V-10
0
10
0
V-11
V-12
V-13
V-14
V-15
V-16
V-17
V-18
V-19
V-20
10
0
V-21
V-22
10
20
0
Corynespora Thanatephorus
cassiicola
Botrytis
cinerea
Fusarium
oxysporum
compd
cucumeris
10
0
V-23
V-24
10
0
10
0
V-1
V-2
V-3
V-4
V-5
V-6
V-7
V-8
V-9
44.52 ( 4.04
31.51 ( 2.22
22.07 ( 1.11
42.45 ( 3.28
43.49 ( 4.15
50.52 ( 4.64
71.56 ( 5.15
52.16 ( 3.25
57.75 ( 4.41
36.00 ( 1.25
12.89 ( 0.75
37.33 ( 1.32
15.97 ( 0.98
34.66 ( 2.22
19.00 ( 1.04
33.31 ( 2.11
39.94 ( 2.36
54.44 ( 1.28
26.33 ( 0.79
37.33 ( 3.14
38.64 ( 2.38
43.75 ( 4.03
24.89 ( 1.85
65.97 ( 5.06
42.49 ( 2.25
59.89 ( 3.33
46.22 ( 4.08
38.35 ( 2.29
56.05 ( 3.33
61.28 ( 5.45
36.59 ( 2.26
64.88 ( 3.19
70.36 ( 2.16 44.58 ( 3.17
60.36 ( 2.06 7.63 ( 0.79
58.47 ( 3.25 49.43 ( 2.55
64.00 ( 4.04 44.58 ( 3.31
66.62 ( 3.18 41.22 ( 2.29
63.55 ( 2.78 45.40 ( 6.05
10
0
V-25
V-26
10
10
20
0
10
100
0
RH-5849
10
10
10
0
95.31 ( 8.08 100.00 ( 0.00 92.26 ( 7.78
60.59 ( 4.06
63.33 ( 7.05
70.36 ( 6.52
61.97 ( 5.85
72.73 ( 9.05
63.33 ( 6.79
54.31 ( 3.15 42.33 ( 3.23
62.24 ( 2.25 7.38 ( 1.05
57.28 ( 5.01 1.50 ( 0.13
32.56 ( 2.07 8.82 ( 0.99
37.07 ( 3.31 35.28 ( 2.02
27.89 ( 5.08 15.86 ( 1.12
Table 4. Insecticidal Activity against Plutella xylostella Linnaeus at 600 mg L-1
V-10
V-11
V-12
V-13
V-14
V-15
V-16
V-17
V-18
V-19
V-20
V-21
V-22
V-23
V-24
V-25
V-26
compd
mortality (%)
compd
mortality (%)
comp.
mortality (%)
V-1
V-2
V-3
V-4
V-5
V-6
V-7
V-8
V-9
V-10
0
0
V-11
V-12
V-13
V-14
V-15
V-16
V-17
V-18
V-19
V-20
20
0
V-21
V-22
V-23
V-24
V-25
V-26
CK
0
0
83.10 ( 10.07 41.42 ( 2.15 35.28 ( 1.11
10
0
1
0
53.31 ( 3.25
67.89 ( 6.18
79.25 ( 7.08
64.66 ( 4.86
65.32 ( 5.05
53.31 ( 2.26
60.59 ( 3.34
69.75 ( 5.25
38.64 ( 3.16
75.55 ( 7.05
67.26 ( 6.17
50.22 ( 2.26
0.00 ( 0.00
12.96 ( 2.22 14.47 ( 1.07
48.06 ( 3.16 44.59 ( 3.12
44.79 ( 3.17 42.33 ( 2.24
52.78 ( 3.19 32.83 ( 1.18
34.38 ( 2.78 1.50 ( 0.23
48.87 ( 3.45 14.47 ( 0.75
40.56 ( 4.06 4.46 ( 0.27
25.02 ( 2.12 0.00 ( 0.00
24.05 ( 1.78 -3.03 ( 0.05
55.06 ( 3.37 14.47 ( 1.11
54.31 ( 3.64 25.24 ( 2.18
34.38 ( 3.29 10.25 ( 0.68
1.11 ( 0.15 11.67 ( 0.88
0
0
0
10
10
0
0
0
0
0
0
100
10
10
10
0
fipronila
0
0
a The control fipronil was at 5 mg L-1.
compounds, in which the urea linkage was converted to a
carbamic acid ester. Four kinds of common plant pathogens,
C. cassiicola, T. cucumeris, B. cinerea, and F. oxysporum, were
chosen for bioassay. As shown in Table 5, most compounds
showed good fungicidal activities in vitro against the above four
strains at 50 mg L-1. In general, compounds V-1-V-9, in which
R1 is a 2,6-F2-substituted group, showed higher activities and
broader spectra than compounds in which R1 is a 2,6-Cl2- or
2-Cl-substituted group. Compounds V-4, V-6, V-7, and V-8
displayed higher activities against the four fungus species than
those of the four control fungicides. Particularly, compound V-7
showed excellent activities with inhibitory rates of 71.56, 95.31,
100.0, and 92.26%, respectively, whereas the four commercialized
fungicides, 75% chlorothalonil WP, 3% jingangmycin AS, 40%
pyrimethanil SC, and 70% thiophanate-methyl WP, displayed
23.29, 57.51, 48.90, and 34.21% inhibitory rates correspondingly.
For the title compounds, their fungicidal activities against
T. cucumeris were generally better than those against F. oxysporum.
As chitin is a major component of fungal cell walls, we chose
compound V-21 with a medium inhibitory rate to test if it would
have an effect on the cell wall so as to identify whether the
DMF (control) 1.66 ( 0.75
fungicidesa
23.29 ( 1.25 a 57.51 ( 3.35 b 48.90 ( 2.77 c 34.21 ( 2.28 d
a Control fungicides: a, 75% chlorothalonil WP; b, 3% jingangmycin AS; c, 40%
Pyrimethanil SC; d, 70% thiophanate-methyl WP.
formation of chitin had been disrupted or not. The morphologic
results are shown in Figure 1. Compared with the blank and
fungicide control, the cytoplasm color ofC. cassiicolatreated with
V-21 turned purple, the same color as with the control fungicide
TM. This phenomenon implied that V-21 probably had the same
effect on the cell wall of C. cassiicola as the fungicide control. In
other words, V-21 might disturb the formation of chitin in the cell
wall.
In summary, a novel series of aryl carbamic acid 2-furanmethyl
esters were designed and synthesized on the basis of the lead
compounds B and C. Compared with the lead compounds, the
title compounds showed no insecticidal activity against C. pipiens
pallens and P. xylostellaLinnaeus, but, inspiringly, theypossessed
obvious fungicidal activities against four kinds of common plant

3042 J. Agric. Food Chem., Vol. 58, No. 5, 2010
Li et al.
Figure 1. Morphology observation of cell wall of Corynespora cassiicola disposed by V-21, 5-thiophanate methyl (TM), and CK (DMF).
pathogens. In particular, compounds V-4, V-6, V-7, and V-8
displayed higher activities against the four fungus species than
those of the four control fungicides. Furthermore, the morpho-
logic results suggested that compound V-21 had an effect on the
cell wall of C. cassiicola. The results indicated that the modifica-
tion on the urea linkage of lead compounds was an effective
strategy to discover new candidates as fungicides.
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Received for review July 30, 2009. Revised manuscript received
February 2, 2010. Accepted February 04, 2010. We greatly
acknowledge financial support for this work from the National Key
Project for Basic Research (2003CB114400, 2010CB126104), the
National Natural Science Foundation of China (20872175), and the
National High Technology Research and Development Program of
China (2006AA10A201). We also acknowledge financial support from
the Key Laboratory of Green Pesticide and Agricultural Bioengineering,
Ministry of Education, Guizhou University, Guiyang, People’s Republic
of China.