Synthesis and fungicidal activity of macrolactams and macrolactones with an oxime ether side chain

Article abstract of DOI:10.1021/jf072733+

Three series of novel macrolactams and macrolactones - 12-alkoxyimino- tetradecanlactam, 12-alkoxyiminopentadecanlactam, and 12-alkoxyiminodecanlactone derivatives (7A, 7B, and 7C) - were synthesized from corresponding 12-oxomacrolactams and 12-oxomacrolactone. Their structures were confirmed by ¹H NMR and elemental analysis. The Z and E isomers of 7A and 7B were separated, and their configurations were determined by ¹H NMR. These compounds showed fair to excellent fungicidal activities against Rhizoctonia solani Kuehn. It is interesting that the Z and E isomers of most of the compounds have quite different fungicidal activities. The fact that the compounds have a gradual increase of fungicidal activity in the order of 7A, 7C, and 7B indicated that the macrocyclic derivatives with a hydrogen-bonding acceptor (=N-O-) and a hydrogen-bonding donor (-CONH-) on the ring, and a three methylenes distance (CH₂CH₂CH₂) between these two functional groups, exhibited the best fungicidal activity. The bioassay also showed that 7B not only has good fungicidal activity but also may have a broad spectrum of fungicidal activities.

Full text of DOI:10.1021/jf072733+

J. Agric. Food Chem. 2007, 55, 10857–10863 10857
Synthesis and Fungicidal Activity of Macrolactams
and Macrolactones with an Oxime Ether Side Chain
JIA-XING HUANG,† YUE-MEI JIA,† XIAO-MEI LIANG,† WEI-JUAN ZHU,†
JIAN-JUN ZHANG,† YAN-HONG DONG,† HUI-ZU YUAN,‡ SHU-HUA QI,‡
JIN-PING WU,† FU-HENG CHEN,† AND DAO-QUAN WANG*,†
Key Laboratory of Pesticide Chemistry and Application Technology, Department of Applied
Chemistry, China Agricultural University, Beijing, People’s Republic of China, 100094 and
Institute of Plant Protection, Chinese Academy of Agricultural Science,
Beijing, People’s Republic of China, 100094
Three series of novel macrolactams and macrolactones — 12-alkoxyimino-tetradecanlactam, 12-
alkoxyiminopentadecanlactam, and 12-alkoxyiminodecanlactone derivatives (7A, 7B, and 7C) — were
synthesized from corresponding 12-oxomacrolactams and 12-oxomacrolactone. Their structures were
1
confirmed by H NMR and elemental analysis. The Z and E isomers of 7A and 7B were separated,
and their configurations were determined by 1H NMR. These compounds showed fair to excellent
fungicidal activities against Rhizoctonia solani Kühn. It is interesting that the Z and E isomers of
most of the compounds have quite different fungicidal activities. The fact that the compounds have
a gradual increase of fungicidal activity in the order of 7A, 7C, and 7B indicated that the macrocyclic
derivatives with a hydrogen-bonding acceptor ()N-O-) and a hydrogen-bonding donor (-CONH-)
on the ring, and a three methylenes distance (CH2CH2CH2) between these two functional groups,
exhibited the best fungicidal activity. The bioassay also showed that 7B not only has good fungicidal
activity but also may have a broad spectrum of fungicidal activities.
KEYWORDS: Macrolactam; macrolactone; synthesis; fungicidal activity; fungicide; pesticide
1. INTRODUCTION
the nasopharynx (KB) and against five standard animal tumor
systems, and discodermide (3), maltophilin (4), and xanthobac-
cin A (5), which show antifungal activity. It is also well-known
that avermectins, obtained from the fermentation broth of
Streptomyces aVermitilis, are unique, naturally occurring mac-
rolactones (6) with a broad spectrum of anthelmintic and
insecticidal activities (7). In the search for potential pesticides,
more than ten series of cyclododecane derivatives have been
synthesized, and their biological activities have been evaluated
in our laboratory. Among them, 2-monosubstituted cyclodode-
canone derivatives, such as 1 (8), 2 (9), or 2-monosubstituted
cyclododecanone oxime derivatives, such as 3 (10), were found
to be active against some important agricultural fungi species
(Figure 1). On the contrary, monosubstituted cyclododecane
derivatives, for example, 4, 5, and 6, were found to be
completely ineffective as fungicides (unpublished results).
Pesticides play a key role in our life, not only for crop
protection in agriculture, but also for human health. However,
the unrestricted use of highly toxic pesticides over several
decades has resulted in negative effects on the environment and
poisoning of nontargeted species. To reduce the negative impacts
of the pesticides, new compounds with high efficacy and
selectivity against target species are desirable. Imitating the
chemistry of biologically active natural products is one approach
for developing such pesticides. Macrolactams and macrolactones
are a large family of natural products that are isolated from a
number of sources, including marine sponges, marine bacteria,
and terrestrial bacteria. This class of compounds has attracted
considerable interest of chemists and the natural products
community because they display a diverse range of biological
activities including antitumor, antifungal, cytotoxicity, antimi-
crobial activities, and inhibition of superoxide generation.
Several examples include rifamycin S (1), a potent inhibitor of
DNA-dependent RNA polymerase (RNAP) of E. coli and other
prokaryotes, maytansine (2), which shows significant inhibitory
activity in vitro against cells derived from human carcinoma of
We postulate that the coexistence of two polarizable groups
on the cyclododecane ring is necessary for fungicidal activity
of the cyclododecanone class of compounds. Therefore, our
approach to improving their fungicidal activity through structural
derivation is to use natural macrolactam or marolactone as a
template (the -CONH- or –COO- moiety acts as one
polarizable group). Thus, a series of 12-alkoxyiminotetrade-
canlactams (7A) were synthesized. It is known that there are
two geometric isomers about the C)N bond of oxime deriva-
* Author to whom correspondence should be addressed. Telephone/
fax: 86-10-62732219; e-mail: wangdq@cau.edu.cn.
† China Agricultural University.
‡ Chinese Academy of Agricultural Science.
10.1021/jf072733+ CCC: $37.00
2007 American Chemical Society
Published on Web 12/04/2007

10858 J. Agric. Food Chem., Vol. 55, No. 26, 2007
Huang et al.
physical and elemental data of the target compounds are given in Table
1 (in which the total yields of the Z and E isomers are given), and the 1H
NMR data is presented in Table 2.
2.2.3. General Procedure for the Synthesis of Compounds 7
(Procedure 2). 2.2.3.1. Synthesis of Alkoxyamines. A solution of
triethylamine (1.05 g, 10.3 mmol) in DMF (10 mL) was added to a
solution of alkyl chloride (10 mmol) and N-hydroxy phthalimide (9.3
mmol) in DMF (12 mL) at 0–5 °C. After stirring for 3 days, the mixture
was poured into a 10% hydrochloric acid solution (60 mL), and the
resulting mixture was then filtered. The solid was dissolved in ethanol
(10 mL), and a solution of hydrazine hydrate (10 mmol) in ethanol
was added. The mixture was refluxed for 2 h, cooled, and then filtered.
The filter cake was washed with ethanol. The combined filtrates were
saturated with gaseous hydrochloric acid, and then ether was added
until no further precipitate was observed. Filtration gave a white solid
(alkoxyamine hydrochloride) that was used in the next step without
purification.
Figure 1. Compounds 1-6.
Scheme 1. Synthetic route of the compounds 7
2.2.3.2. Synthesis of Compounds 7. A mixture of compounds 8 (2.5
mmol) and alkoxyamine hydrochloride (4 mmol) in pyridine (10 mL)
was stirred for 16 h, concentrated to 2 mL at reduced pressure, poured
into water (20 mL), and then extracted with methylene chloride (3 ×
20 mL). The combined organic extracts were washed with dilute
hydrochloride acid, water, and brine successively, dried over sodium
sulfate, and evaporated to give a white solid, which was purified and
separated by the same procedure as in Section 2.2.2.
2.3. Bioassay of Fungicidal Activities. 2.3.1. Method. Fungicidal
activities of compounds 7 against Rhizoctonia solani Kühn were
evaluated using the mycelium growth rate test (17).
2.3.2. Fungicidal ActiVities of Compounds 7. Inhibition rate of
compounds 7 against Rhizoctonia solani Kühn at the concentrations
of 100, 50, 25, 12.5 and 6.25 µg/mL was first determined. Then, EC50
values were estimated using logistic analysis (18). As a control,
fungicidal activity of the commercial fungicide carbendazim against
the above-mentioned fungi was evaluated at the same condition. The
results are shown in Table 3.
2.3.3. Spectrum of Fungicidal ActiVities of Compound 7B3. Inhibi-
tion rate of compounds 7B3 (a mixture of Z and E isomers) against
pear black spot (Alternaria kikuchiana), tomato southern blight
(Phyllospicpa physaleos Sacc), cotton rhizoctonia rot (Rhizoctonia
solani Kühn), cucumber gray mold (Botrytis cinerea Pers), asparagus
stem blight (Phomopsis asparagi Sacc), apple ring spot (Physalospora
piricola Nose), cotton verticillium wilt (Vercicillium alboatrum Reinke
et Berthold), cucumber anthracnose (Colletotrichum lagenarium), cotton
fusarium wilt (Fusarium Vasinfectum Atkimson), cotton damping-off
(Pythium aphanibermatum (Eds.) Fipzp), tomato early blight (Alternaria
solani Jones et Grout), tomato leaf mold (Cladosporium fulVum Cooke),
peppers fruit rot (Phytophthora capsici Len) at concentrations of 100,
50, 25, 12.5, and 6.25 µg/mL was determined and then EC50 values
were estimated. The results were shown in Table 4.
tives and that they may have different biological activities (11, 12).
Therefore, Z and E isomers of compounds 7A were separated,
and their fungicidal activities against cotton soreshin (Rhizoc-
tonia solani Kühn), an important agricultural fungus species,
were evaluated. At the same time, their pentadecanlactam and
pentadecanlactone analogous (7B and 7C) were also synthesized
to study the effect of lactam and lactone rings, as well as the
distance between the oxime and amide/ester functional groups
on their fungicidal activities. Then, a very active representative
of 7B was screened against 13 important agricultural fungi. The
synthetic route of the compounds 7 is shown in Scheme 1.
Compounds 7 were prepared from compounds 8 (13–15) by
reaction with hydroxylamine hydrochloride to give compounds
9, which were then alkylated using alkyl or benzyl halides
(Procedure 1) or directly from compounds 8 by reaction with
alkoxyamines (Procedure 2).
2. MATERIALS AND METHODS
2.1. General. NMR spectra were recorded in CD3COCD3 or CDCl3
with a Bruker DPX300 spectrometer, using TMS as internal standard;
elemental analysis was performed by the analytical center at the Institute
of Chemistry (Beijing), Chinese Academy of Science; melting points
were measured on a Yanagimoto melting-point apparatus and are
uncorrected. The solvents and reagents were used as received or were
dried prior to use as needed.
2.2. Chemical Synthesis. 2.2.1. General Procedure for the Syn-
thesis of Compounds 9. To a stirred solution of compound 8 (0.01 mol)
and sodium carbonate (1.06 g, 0.01 mol) in 20 mL of methanol, a
solution of hydroxylamine hydrochloride (0.76 g, 0.011 mol) in 5 mL
of water was added dropwise. After the mixture was refluxed for 4 h,
cold water was added. Filtration gave a mixture of Z and E isomers of
9. 9A: yield: 90%, m.p.:152–154°; 9B: yield: 87%, m.p.:162–164°; 9C:
yield: 93%, m.p.: 57∼62°. 9A, 9B, and 9C were used in the next step
without purification.
2.2.2. General Procedure for the Synthesis of Compounds 7 (Procedure
1) (16). A mixture of compound 9 (2 mmol) and sodium hydride (0.10 g,
2.2 mmol) in anhydrous DMSO was stirred at room temperature for 1.5 h,
an alkyl halide (2.2 mmol) was then added dropwise, and the mixture was
stirred for 6 h at room temperature. The excess sodium hydride was
destroyed by carefully adding 20 mL water, and then the mixture was
extracted with methylene chloride (3 × 20 mL). The combined organic
layer was washed with brine, dried over sodium sulfate, and then
concentrated under vacuum to give a crude product. Further purification
on silica gel column chromatography with methylene chloride and ethyl
acetate gave Z and E isomers of the target compounds, and the minor
mixture in the order of Z isomer (1), mixture, and then E isomer (2). The
3. RESULTS AND DISCUSSION
3.1. Geometric Isomers of Compounds 7. The Z and E
isomers of compounds 7A and 7B (Figure 2) were isolated by
column chromatography and were distinguished based on the
1H NMR features of the compounds.
In the case of the Z isomers, the electronegative oxygen atom
on the side chain is closer to 13-CH2 and further away from
the 11-CH2. The resonance lines of 13-CH2 would be expected
to shift downfield and that of 11-CH2 shifted upfield from the
corresponding CH2 of the E isomers. Taking 7A3 as an example,
the resonance peak corresponding to 11-CH2 displayed a triplet
at δ 2.2, and that of 13-CH2 was a multiplet at δ 2.52–2.57 in
the spectrum of 7A3 (1), but the corresponding two CH2 in 7A3
(2) displayed a multiplet due to the downfield shift of the 11-
CH2 peak and the upfield shift of the 13-CH2 peak. Therefore,
7A3 (1) is the Z isomer and 7A3 (2) is the E isomer. The Z and
E isomers of compounds 7C could not be separated because of
an insufficient polarity difference.

Synthesis and Fungicidal Activity of Macrolactams and Macrolactones
J. Agric. Food Chem., Vol. 55, No. 26, 2007 10859
Table 1. Physical and Elemental Data of Compounds 7
elemental analysis
compd No.
R
configuration
mp (°)
yield (%)
90b (50a)
C (calcd)
H (calcd)
N (calcd)
7A-1(1)
7A-1(2)
7A-2(1)
7A-2(2)
7A-3(1)
7A-3(2)
7A-4(1)
7A-4(2)
7A-5(1)
7A-5(2)
7A-6(1)
7A-6(2)
7A-7(1)
7A-7(2)
7A–8(1)
7A–8(2)
7A-9(1)
7A–9(2)
7A1–0(1)
7A1–0(2)
7A–11(1)
7A–11(2)
7A–12(1)
7A–12(2)
7A–13(1)
7A–13(2)
7A–14(1)
7A–14(2)
7A–15(1)
7A–15(2)
7A–16(1)
7A–16(2)
7A–17(1)
7A–17(2)
7B-2(1)
7B-2(2)
7B-3(1)
7B-3(2)
7B–4(1)
7B–4(2)
7B-5(1)
7B-5(2)
7B–7(1)
7B–7(2)
7B–9(1)
7B–9(2)
7B–10(1)
7B–10(2)
7B–13(1)
7B–13(2)
7B–15(1)
7B–15(2)
7C-3
Me
Me
ethyl
ethyl
n-propyl
n-propyl
allyl
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z
E
Z+E
Z+E
Z+E
Z+E
Z+E
Z+E
Z+E
Z+E
107–108
71–72
112–113
72–73
82
68
90–91
74–75
89–90
54–55
93–94
71–72
74–75
55–56.5
73.5–74
68–68.5
76–77
69–70
118–119
97–99
67.43 (67.13)
67.30 (67.13)
68.46 (68.04)
67.67 (68.04)
68.87 (68.88)
68.88 (68.88)
69.39 (69.35)
69.33 (69.35)
69.62 (69.63)
69.58 (69.63)
69.66 (69.63)
69.61 (69.63)
71.52 (71.54)
71.51 (71.54)
74.61 (74.61)
74.75 (74.61)
75.33 (75.26)
75.22 (75.26)
73.45 (73.22)
73.24 (73.22)
73.65 (73.70)
73.74 (73.70)
69.86 (69.58)
69.41 (69.58)
66.56 (66.56)
66.63 (66.56)
64.71 (64.76)
64.77 (64.76
63.47 (63.54)
63.70 (63.54)
60.91 (61.02)
61.01 (61.02)
69.33 (69.53)
69.42 (69.53)
69.43 (68.88)
68.67 (68.88)
70.14 (69.63)
69.71 (69.63)
70.40 (70.09)
70.13 (70.09)
70.65 (70.32)
69.08 (70.32)
72.19 (72.08)
71.84 (72.08)
75.66 (75.55)
75.39 (75.55)
73.80 (73.70)
73.69 (73.70)
67.26 (67.24)
67.15 (67.24)
64.57 (64.30)
64.26 (64.30)
69.53 (69.41)
69.84 (69.86)
69.70 (70.11)
72.26 (71.89)
75.33 (75.40)
73.76 (73.50)
67.07 (67.07)
63.74 (64.14)
10.55 (10.52)
10.42 (10.52)
10.77 (10.71)
10.72 (10.71)
10.91 (10.88)
10.83 (10.88)
10.23 (10.27)
10.29 (10.27)
11.07 (11.04)
11.07 (11.04)
11.08 (11.04)
10.89 (11.04)
11.33 (11.44)
11.49 (11.44)
11.92 (12.08)
12.13 (12.08)
12.20 (12.21)
12.14 (12.21)
9.48 (9.36)
9.37 (9.36)
9.54 (9.56)
9.57 (9.56)
8.64 (8.62)
8.62 (8.62)
8.29 (8.25)
8.33 (8.25)
8.08 (8.02)
7.97 (8.02)
7.54 (7.62)
7.73 (7.62)
7.30 (7.31)
7.37 (7.31)
9.03 (9.04)
8.79 (9.04)
11.07 (10.88)
10.76 (10.88)
11.31 (11.04)
10.98 (11.04)
10.54 (10.46)
10.48 (10.46)
11.31 (11.18)
11.03 (11.18)
11.94 (11.55)
11.63 (11.55)
12.46 (12.27)
12.43 (12.27)
9.70 (9.56)
10.42 (10.44)
10.35 (10.44)
10.11 (9.92)
9.75 (9.92)
9.46 (9.45)
9.51 (9.45)
9.58 (9.51)
9.41 (9.51)
9.13 (9.02)
9.08 (9.02)
9.01 (9.02)
8.98 (9.02)
7.88 (7.95)
8.01 (7.95)
6.22 (6.21)
6.33 (6.21)
5.95 (5.85)
5.92 (5.85)
8.28 (8.13)
8.47 (8.13)
7.93 (7.81)
7.68 (7.81)
7.75 (7.73)
7.83 (7.73)
7.36 (7.39)
7.42 (7.39)
10.75 (10.79)
10.69 (10.79)
7.02 (7.06)
7.05 (7.06)
6.73 (6.78)
6.75 (6.78)
11.83 (12.16)
12.31 (12.16)
9.24 (9.45)
9.04 (9.45)
9.04 (9.02)
9.03 (9.02)
8.86 (9.08)
8.77 (9.08)
8.68 (8.63)
8.58 (8.63)
7.42 (7.64)
7.57 (7.64)
5.50 (5.68)
5.65 (5.68)
7.70 (7.81)
7.87 (7.81)
6.96 (7.13)
6.95 (7.13)
6.60 (6.82)
6.69 (6.82)
4.42 (4.50)
4.66 (4.53)
4.00 (4.30)
3.59 (3.81)
2.60 (2.84)
3.61 (3.90)
3.69 (3.56)
3.23 (3.40)
90b
93b
92b
98b
92b
96b
96b
97b
92b
94b
97b
96b
90b
90b
91b
95b
67a
71a
75a
71a
73a
80a
80a
88a
82a
allyl
n-butyl
n-butyl
i-butyl
i-butyl
n-heptal
n-heptal
n-tetradecyl
n-tetradecyl
n-hexadecyl
n-hexadecyl
benzyl
benzyl
4-methylbenzyl
4-methylbenzyl
4-fluorobenzyl
4-fluorobenzyl
4-chlorobenzyl
4-chlorobenzyl
4-nitrobenzyl
4-nitrobenzyl
2-chloro-6-fluorobenzyl
2-chloro-6-fluorobenzyl
2,4-dichlorobenzyl
2,4-dichlorobenzyl
3-pyridylmethyl
3-pyridylmethyl
ethyl
128–130
97–98
118–119
92–93
131.5–132
110–111
148–149
134–135
145–146
93–94
131–132
129–130
108–110
81–82
89–90
ethyl
n-propyl
n-propyl
allyl
allyl
n-butyl
n-butyl
n-heptal
n-heptal
118–119
107–108
92–93.5
90–92
96–97
79–80.5
70–71
64–65
69–71
80–81
82–83.5
80–81
86–87
114–115
116–117
123–124
136–137
viscous liquid
viscous liquid
viscous liquid
viscous liquid
viscous liquid
viscous liquid
viscous liquid
viscous liquid
n-hexadecyl
n-hexadecyl
benzyl
benzyl
9.55 (9.56)
8.29 (8.46)
8.47 (8.46)
7.91 (7.85)
7.90 (7.85)
10.61 (10.68)
9.93 (10.10)
10.45 (10.84)
11.02 (11.24)
11.51 (12.04)
9.70 (9.25)
4-chlorobenzyl
4-chlorobenzyl
2-chloro-6-fluorobenzyl
2-chloro-6-fluorobenzyl
n-propyl
40a
45a
50a
42a
55a
45a
46a
51a
7-C4
7-C5
7-C7
7-C9
7C–10
7C–13
7C–15
allyl
n-butyl
n-heptal
n-hexadecyl
benzyl
4-chlorobenzyl
2-chloro-6-fluorobenzyl
8.48 (8.19)
7.58 (7.59)
a Procedure 1. b Procedure 2.
3.2. Fungicidal Activity. As shown in Table 3, compounds
7A have fair to good fungicidal activity against Rhizoctonia
solani Kühn. Among them, compounds 7A3 (2), 7A5 (2),
and 7A10 (2), the EC50 values of which were 9.11, 7.21,
and 7.24 µg/mL, respectively, displayed the highest fungicidal
activity, but they were inferior to the commercial fungicide
carbendazin. In general, the following structure–activity
relationship in compounds 7A was observed: (1) the com-
pounds with a C3-C4 straight chain alkyl and benzyl without
substituents have better fungicidal activity; (2) E isomers are
more active than Z isomers, except for the individual
compounds 7A14. The replacement of the tetradecanlactam
ring with a pentadecanlactam ring (compounds 7B) results
in significantly improved fungicidal activity. The EC50 values
of compounds 7B3(2), 7B5(1), 7B5(2), and 7B15(1) were
3.62, 3.97, 2.34, and 2.34 µg/mL, respectively, and are

10860 J. Agric. Food Chem., Vol. 55, No. 26, 2007
Table 2. 1H NMR Data of Compounds 7 (CDCl3, δ)
Huang et al.
compds No.
7A-1(1)
11-CH2
13-CH2
others
2.14–2.24 (4H, m) (+2-CH2)
2.51–2.55 (2H, m)
1.23–1.42 (12H, m), 1.57–1.72 (4H, m), 3.44–3.50 (2H, m), 3.87
(3H, s), 6.14 (1H, br s)
7A-1(2)
7A-2(1)
7A-2(2)
7A-3(1)
2.31 (2H, t, J ) 6.5 Hz)
2.23 (2H, t, J ) 6.9 Hz)
2.38 (2H, t, J ) 5.4 Hz)
1.23–1.37 (12H, m), 1.51–1.60 (2H, m), 1.60–1.66 (2H, m),
2.17–2.22 (2H, m), 3.53–3.49 (2H, m), 3.85 (3H, s), 6.25 (1H, br, s)
1.56–1.70 (4H, m), 1.23–1.41 (15H, m), 2.12–2.16 (2H, m)
3.43–3.50 (2H, m), 4.13 (2H, q, J ) 6.9 Hz), 6.26 (1H, br)
1.24–1.30 (15H, m), 1.54–1.68 (4H, m), 2.17–2.21 (2H, m),
3.54–3.59 (2H, m), 4.10 (2H, q, J ) 7.0 Hz,), 6.28 (1H, br)
0.97 (3H, t, J ) 7.4 Hz), 1.20–1.42 (12H, m),
2.52–2.56 (2H, m)
2.30–2.40 (4H, m)
2.22 (2H, t, J ) 7.0 Hz)
2.52–2.57 (2H, m)
1.50–1.78 (6H, m), 2.10–2.17 (2H, m), 3.43–3.50 (2H, m), 4.03
(2H, t, J ) 6.8 Hz), 6.23 (1H, br)
7A-3(2)
7A-4(1)
7A-4(2)
7A-5(1)
7A-5(2)
7A–6(1)
7A-6(2)
7A-7(1)
2.30–2.40 (4H, m)
0.98 (3H, t, J ) 7.4 Hz), 1.23–1.29 (12H, m),
1.51–1.75 (6H, m), 2.15–2.21 (2H, m), 3.50–3.60 (2H, m), 4.00 (2H, t,
J ) 6.6 Hz), 6.26 (1H, br)
1.23–1.39 (12H, m), 1.58–1.72 (4H, m),
2.21–2.26 (2H, m)
2.54–2.59 (2H, m)
2.12–2.16 (2H, m), 3.44–3.50 (2H, m), 4.55–4.59 (2H, m), 5.21–5.37
(2H, m), 5.99–6.09 (1H, m), 6.29 (1H, br)
1.26–1.35 (12H, m), 1.55–1.68 (4H, m),
2.32–2.39 (4H, m)
2.13–2.18 (2H, m), 3.52–3.58 (2H, m), 4.54–4.59 (2H, m), 5.21–5.37
(2H, m), 5.95–6.08 (1H, m), 6.30 (1H, br, s)
0.96 (3H, t, J ) 7.4 Hz), 1.20–1.46
(14H, m), 1.57–1.72 (6H, m), 2.12–2.17 (2H, m), 3.43–3.50 (2H, m), 4.07
2.22 (2H, t, J ) 6.9 Hz)
2.51–2.56 (2H, m)
(2H, t, J ) 6.7 Hz), 6.24 (1H, br)
2.29–2.39 (4H, m)
0.96 (3H, t, J ) 7.3 Hz), 1.25–1.57 (14H, m), 1.57–1.70 (6H, m),
2.16–2.21 (2H, m), 3.53–3.59 (2H, m), 4.05 (2H, t,
J ) 6.45 Hz), 6.29 (1H, br)
2.22 (2H, t, J ) 7.0 Hz)
2.53–2.57 (2H, m)
0.96 (6H, d, J ) 6.7 Hz), 1.24–1.39 (12H, m) 1.54–1.70 (4H, m), 1.95–2.05
(1H, m), 2.12–2.17 (2H, m), 3.45–3.51 (2H, m), 3.85 (2H, d,
J ) 6.7 Hz), 6.18 (1H, br)
0.96 (6H, d, J ) 6.7 Hz), 1.26–1.35 (12H, m), 1.55–1.70 (4H, m),
1.93–2.03 (1H, m), 2.15–2.20 (2H, m), 3.53–3.59
(2H, m), 3.82 (2H, d, J ) 6.6 Hz), 6.26 (1H, br)
0.86–0.91 (3H, t, J ) 6.7), 1.23–1.40 (20H, m),
1.59–1.73 (6H, m), 2.12–2.17 (2H, m), 3.43–3.49 (2H, m),
4.06 (2H, t, J ) 6.8 Hz), 6.23 (1H, br)
0.87–0.91 (3H, t, J ) 6.8), 1.26–1.41 (26H, m), 2.16–2.21 (2H, m),
3.53–3.59 (2H, m), 4.03 (2H, t, J ) 6.6 Hz), 6.27 (1H, br)
0.88 (3H, t, J ) 6.7 Hz), 1.20–1.41 (34H, m), 1.55–1.73 (6H, m),
2.13–2.17 (2H, m), 3.43–3.49 (2H, m), 4.05 (2H, t,
J ) 6.8 Hz), 6.22 (1H, br)
0.88 (3H, t, J ) 6.9 Hz), 1.26–1.40 (34H, m), 1.50–1.78 (6H, m),
2.16–2.20 (2H, m), 3.53–3.59 (2H, m), 4.03 (2H, t,
J ) 6.53 Hz), 6.26 (1H, br)
2.31–2.40 (4H, m)
2.22 (2H, t, J ) 6.9 Hz)
2.22 (2H, t, J ) 6.9 Hz)
2.51–2.56 (2H, m)
7A-7(2)
7A-8(1)
2.29–2.39 (4H, m)
2.52–2.56 (2H, m)
7A-8(2)
2.29–2.39 (4H, m)
7A-9(1)
2.22 (2H, t, J ) 6.92 Hz)
2.51–2.56 (2H, m)
0.88 (3H, t, J ) 6.7 Hz), 1.20–1.42 (38H, m), 1.55–1.72 (6H, m),
2.10–2.16 (2H, m), 3.43–3.49 (2H, m), 4.05 (2H, t,
J ) 6.81 Hz), 6.22 (1H, br)
7A-9(2)
2.30–2.39 (4H, m)
0.88 (3H, t, J ) 6.8 Hz), 1.26–1.40 (38H, m), 1.50–1.71 (6H, m),
2.16–2.21 (2H, m), 3.53–3.59 (2H, m), 4.03 (2H, t,
J ) 6.53 Hz), 6.27 (1H, br)
7A-10(1)
7A-10(2)
7A-11(1)
7A-11(2)
7A-12(1)
7A-12(2)
7A-13(1)
2.20 (2H, t, J ) 6.9 Hz)
2.53–2.57 (2H, m)
1.18–1.40 (12H, m), 1.54–1.65 (4H, m), 1.91–1.95 (2H, m),
3.40–3.46 (2H, m), 5.09 (2H, s), 5.98
(1H, br), 7.26–7.42 (5H, m)
1.08–1.20 (12H, m), 1.39–1.58 (4H, m), 1.84–1.90 (2H, m),
3.40–3.52 (2H, m), 5.05 (2H, s), 5.82
2.28–2.36 (4H, m)
(1H, br), 7.26–7.41 (5H, m)
2.22 (2H, t, J ) 6.8 Hz)
2.51–2.56 (2H, m)
1.16–1.34 (12H, m), 1.55–1.63 (4H, m), 1.89–1.92 (2H, m),
2.35 (3H, s), 3.38–3.44 (2H, m), 5.04 (2H, s) 5.99 (1H, br),
7.18 (2H, d, J ) 7.5 Hz), 7.24–7.31 (2H, m)
1.06–1.26 (12H, m), 1.38–1.45 (2H, m), 1.50–1.56 (2H, m),
1.82–1.86 (2H, m), 2.35 (3H, s), 3.45–3.51 (2H, m), 5.00
(2H, s), 5.80 (1H, br), 7.2 (2H, d, J ) 7.7 Hz),7.26–7.31 (2H, m)
1.15–1.39 (12H, m), 1.54–1.66 (4H, m), 1.95–1.99 (2H, m),
3.40–3.46 (2H, m), 5.04 (2H, s), 5.94 (1H, br),
7.34–7.40 (2H, m), 7.02–7.09 (2H, m)
1.11–1.29 (12H, m), 1.44–1.59 (4H, m), 1.90–1.95 (2H, m),
3.47–3.53 (2H, m), 5.01 (2H, s), 5.81 (1H, br),
7.02–7.10 (2H, m), 7.33–7.39 (2H, m)
1.15–1.38 (12H, m), 1.55–1.67 (4H, m), 1.96–2.05 (2H, m),
3.41–3.47 (2H, m), 5.04 (2H, s), 5.75 (1H, br), 7.33 (4H, s)
2.26–2.34 (4H, m)
2.21 (2H, t, J ) 7.0 Hz)
2.52–2.56 (2H, m)
2.29–2.35 (4H, m)
2.21 (2H, t, J ) 7.0 Hz)
2.52–2.56 (2H, m)

Synthesis and Fungicidal Activity of Macrolactams and Macrolactones
J. Agric. Food Chem., Vol. 55, No. 26, 2007 10861
Table 2. Continued
compds No.
7A–13(2)
11-CH2
13-CH2
others
2.29–2.35 (4H, m)
1.11–1.28 (12H, m), 1.42–1.60 (4H, m), 1.88–1.93 (2H, m),
3.45–3.51 (2H, m), 5.00 (2H, s), 5.75 (1H, br), 7.33 (4H, s)
1.23–1.37 (12H, m), 1.53–1.66 (4H, m), 2.04–2.10 (2H, m),
3.48–3.54 (2H, m), 5.17 (2H, s), 5.84 (1H, br), 7.51–7.55 (2H, m),
8.20–8.25 (2H, m)
1.14–1.25 (12H, m), 1.43–1.60 (4H, m), 1.92–2.05 (2H, m),
3.47–3.52 (2H, m), 5.16 (2H, s), 5.77 (1H, br), 7.53–7.57
(2H, m), 8.22–8.26 (2H, m)
1.10–1.30 (12H, m), 1.56–1.65 (4H, m), 2.03–2.07 (2H, m),
3.38–3.44 (2H, m), 5.25 (2H, d, JH–F ) 1.9 Hz), 5.94 (1H, br),
7.00–7.07 (1H, m), 7.20–7.32 (2H, m)
1.00–1.24 (12H, m), 1.43–1.60 (4H, m), 2.02–2.08 (2H, m),
3.48–3.55 (2H, m), 5.26 (2H, d, JH–F ) 1.9 Hz), 6.14 (1H, br),
7.20–7.30 (2H, m), 7.01–7.07 (1H, m)
7A–14(1)
7A–14(2)
7A–15(1)
7A–15(2)
7A–16(1)
7A–16(2)
7A–17(1)
7A–17(2)
7B–2(1)
7B–2(2)
7B–3(1)
7B–3(2)
7B–4(1)
7B–4(2)
2.21 (2H, t, J ) 7.3 Hz)
2.56–2.60 (2H, m)
2.34–2.40 (4H, m)
2.20 (2H, t, J ) 6.7 Hz)
2.51–2.56 (2H, m)
2.55–2.59 (2H, m)
2.54–2.57 (2H, m)
2.27–2.32 (4H, m)
2.21 (2H, t, J ) 7.0 Hz)
1.18–1.36 (12H, m), 1.54–1.66 (4H, m), 2.04–2.07 (2H, m),
3.44–3.50 (2H, m), 5.14 (2H, s), 5.88 (1H, br),
7.37–7.42 (2H, m), 7.23–7.27 (1H, m)
2.31–2.36 (4H, m)
1.11–1.28 (12H, m), 1.44–1.57 (4H, m), 1.97–2.05 (2H, m),
3.47–3.54 (2H, m), 5.13 (2H, s), 5.88 (1H, br), 7.37–7.43
(2H, m), 7.24–7.28 (1H, m)
1.13–1.40 (12H, m), 1.55–1.66 (4H, m), 2.00–2.05 (2H, m),
3.42–3.51 (2H, m), 5.10 (2H, s), 5.94 (1H, br), 7.27.7.33 (1H, m),
7.71–7.74 (1H, m), 8.57–8.65 (2H, m)
1.12–1.61 (16 h, m), 1.97–2.05 (2H, m), 3.48–3.54 (2H, m),
5.07 (2H, s), 5.84 (1H, br), 7.27–7.34 (1H, m), 7.72
(1H, d, J ) 7.8 Hz), 8.58–8.66 (2H, m)
1.17 (t, J ) 7.2 Hz, 3H), 1.28–1.35 (m, 12H), 1.43–1.50
(m, 2H), 1.60–1.71 (m, 4H), 3.20–3.26 (m, 2H), 3.98
(q, J ) 7.2 Hz, 2H), 7.23 (s, 1H)
2.21 (2H, t, J ) 7.1 Hz)
2.31–2.36 (4H, m)
2.08–2.17 (m, 4H) (+2- CH2)
2.13–2.19 (m, 4H) (+2- CH2)
2.08–2.17 (m, 4H) (+2- CH2)
2.13–2.22 (m, 4H) (+2- CH2)
2.06–2.10 (m, 4H) (+2- CH2)
2.10–2.20 (m, 4H) (+2- CH2)
2.27–2.33 (m, 2H)
2.22–2.29 (m, 2H)
2.28–2.34 (m, 2H)
2.25–2.30 (m, 2H)
2.28–2.32 (m, 2H)
2.23–2.32 (m, 2H)
1.17 (t, J ) 7.2 Hz, 3H), 1.20∼1.38 (m, 12H), 1.43–1.50
(m, 2H), 1.60–1.72 (m,4H), 3.23–3.29 (m, 2H), 3.98
(q, J ) 7.2 Hz, 2H), 7.23 (s, 1H)
0.89 (t, J ) 7.5 Hz, 3H), 1.25∼1.34 (m, 12H), 1.37–1.50
(m, 2H), 1.55–1.71 (m, 6H), 3.20–3.26 (m, 2H),
3.90 (t, J ) 6.3 Hz, 2H), 7.22 (s, 1H)
0.89 (t, J ) 7.5 Hz, 3H), 1.24∼1.33 (m, 12H),
1.49–1.72 (m, 8H), 3.23–3.29 (m, 2H), 3.89
(t, J ) 6.3 Hz, 2H), 7.22 (s, 1H)
1.21–1.78 (m, 20H), 3.19–3.29 (m, 2H), 4.45–4.48 (m, 2H),
5.10–5.15 (m, 1H), 5.20–5.27 (m, 1H),
5.91–6.03 (m, 1H), 7.25 (s, 1H)
1.21–1.78 (m, 20H), 3.21–3.31 (m, 2H), 4.45–4.48 (m, 2H),
5.09–5.14 (m, 1H), 5.20–5.27 (m, 1H),
5.90–6.03 (m, 1H), 7.17 (s, 1H)
0.91 (t, J ) 7.2 Hz, 3H), 1.33–1.72 (m, 24H), 3.20–3.26
(m, 2H), 3.95 (t, J ) 6.0 Hz, 3H), 7.20 (s, 1H)
0.91 (t, J ) 7.2 Hz, 3H), 1.33–1.72 (m, 24H), 3.23–3.29
(m, 2H), 3.94 (t, J ) 6.6 Hz, 3H), 7.20 (s, 1H)
7B–5(1)
7B–5(2)
7B–7(1)
7B-7(2)
7B–9(1)
2.04–2.14 (m, 4H) (+2- CH2)
2.13–2.19 (m, 4H) (+2- CH2)
2.08–2.18 (m, 4H) (+2- CH2)
2.10–2.22 (m, 4H) (+2- CH2)
2.11–2.16 (m, 4H) (+2- CH2)
2.16–2.33 (m, 2H)
2.21–2.29 (m, 2H)
2.22–2.32 (m, 2H)
2.20–2.28 (m, 2H)
2.28–2.34 (m, 2H)
0.88 (t, J ) 6.8 Hz), 1.24–1.33 (m, 21H), 1.49–1.72 (m, 8H),
3.21–3.31 (m, 2H), 3.94 (t, J ) 6.5 Hz, 2H), 7.16 (s, 1H)
0.88 (t, J ) 6.8 Hz, 3H), 1.23–1.33 (m, 21H), 1.48–1.72
(m, 8H), 3.21–3.31 (m, 2H), 3.95 (t, J ) 6.5 Hz, 2H), 7.17 (s, 1H)
0.88 (t, J ) 6.7 Hz, 3H), 1.27–1.35 (m, 42H), 1.43–1.51
(m, 2H), 1.59–1.71 (m, 6H), 3.20–3.26 (m, 2H), 3.95 (t,
J ) 6.5 Hz, 2H), 7.19 (s, 1H)
0.88 (t, J ) 6.6 Hz, 3H), 1.27–1.35 (m, 40H), 1.47–1.74
(m, 9H), 3.23–3.29 (m, 2H), 3.95 (t, J ) 6.5 Hz, 2H), 7.16 (s, 1H)
1.25∼1.32 (m, 12H), 1.47–1.50 (m, 2H), 1.60–1.73 (m, 4H),
3.20–3.26 (m, 2H), 4.97 (s, 2H), 7.22 (s, 1H), 7.24–7.39 (m, 5H)
1.22∼1.31 (m, 12H), 1.45–1.53 (m, 2H), 1.55–1.71 (m, 4H),
3.24–3.28 (m, 2H), 5.02 (s, 2H), 7.19 (s, 1H), 7.24–7.37 (m, 5H)
1.22∼1.29 (m, 12H), 1.39–1.49 (m, 2H), 1.57–1.67 (m, 4H),
3.19–3.26 (m, 2H), 5.01 (s, 2H), 7.18 (s, 1H), 7.29–7.45 (m, 4H)
1.22∼1.28 (m, 12H), 1.41–1.54 (m, 2H), 1.59–1.72 (m, 4H),
3.20–3.27 (m, 2H), 5.01 (s, 2H), 7.18 (s, 1H), 7.29–7.45 (m, 4H)
1.21∼1.38 (m, 12H), 1.43–1.49 (m, 2H), 1.57–1.67 (m, 4H),
3.15–3.21 (m, 2H), 5.16 (d, JH–F ) 1.7, 2H), 7.12–7.41 (m, 4H)
1.25∼1.39 (m, 12H), 1.40–1.51 (m, 2H), 1.59–1.70 (m, 4H), 3.21–3.27
(m, 2H), 5.16 (d, JH–F ) 1.7 Hz, 2H), 7.12–7.41 (m, 4H)
7B–9(2)
2.13–2.19 (m, 4H) (+2-CH2)
2.09–2.16 (m, 4H) (+2-CH2)
2.13–2.23 (m, 4H) (+2-CH2)
2.09–2.16 (m, 4H) (+2-CH2)
2.12–2.22 (m, 4H) (+2-CH2)
2.06–2.14 (m, 4H) (+2– CH2)
2.10–2.20 (m, 4H) (+2-CH2)
2.22–2.30 (m, 2H)
2.33–2.39 (m, 2H)
2.29–2.34 (m,2H)
2.32–2.38 (m, 2H)
2.24–2.36 (m, 2H)
2.25–2.31 (m, 2H)
2.21–2.26 (m, 2H)
7B–10(1)
7B–10(2)
7B–13(1)
7B–13(2)
7B–15(1)
7B–15(2)

10862 J. Agric. Food Chem., Vol. 55, No. 26, 2007
Table 2. Continued
Huang et al.
compds No.
7C–3
11-CH2
13-CH2
others
0.90∼0.95 (m, 3H), 1.33∼1.34 (m, 12H), 1.50∼1.52 (m, 2H), 1.61∼1.68 (m, 4H), 1.86∼1.89 (m, 2H), 2.12∼2.17 (m, 2H), 2.24∼2.42 (m, 5H),
3.93∼3.98 (m, 2H), 4.13∼4.18 (m, 2H)
7C–4
1.32∼1.41 (m, 12H), 1.52∼1.54 (m, 2H), 1.63∼1.65 (m, 2H), 1.83∼1.88 (m, 2H), 2.13∼2.18 (m, 1H), 2.25∼2.43 (m, 5H), 4.09∼4.16 (m, 2H),
4.46∼4.97 (m, 2H), 5.10∼5.15 (m, 1H), 5.20∼5.27 (m, 1H), 5.92∼6.02 (m, 1H)
7C–5
7C–7
0.93 (t, 3H, J ) 7.3 Hz), 1.26∼1.41 (m, 14H), 1.49∼1.69 (m, 7H), 1.85∼1.90 (m, 2H), 2.25∼2.37 (m, 5H), 3.97∼4.02 (m, 2H), 4.12∼4.18 (m, 2H)
0.86–0.92 (m, 3H), 1.25–1.33 (m, 22H), 1.49–1.54 (m, 2H), 1.61–1.69 (m, 2H), 1.82–1.92 (m, 2H), 2.24–2.37 (m, 6H), 3.96–4.00 (m, 2H),
4.14–4.18 (m, 2H)
7C–9
0.86–0.95 (m, 3H), 1.25–1.35 (m, 40H), 1.49–1.54 (m, 2H), 1.57–1.68 (m, 2H), 1.84–1.92 (m, 2H), 2.24–2.37 (m, 6H), 3.96–4.00 (m, 2H),
4.15–4.20 (m, 2H)
7C–10
7C–13
7C–15
1.31∼1.35 (m, 12H), 1.48∼1.54 (m, 2H), 1.58∼1.68 (m, 2H), 1.83∼1.90 (m, 2H), 2.13∼2.18 (m, 1H), 2.25∼2.45 (m, 5H), 4.06∼4.17 (m, 2H),
5.05 (d, 2H, J ) 2.8 Hz), 7.26∼7.35 (m, 5H)
1.26∼1.33 (m, 12H), 1.47∼1.53 (m, 2H), 1.59∼1.68 (m, 2H), 1.81∼1.90 (m, 2H), 2.24∼2.36 (m, 5H), 4.15 (t, 2H, J ) 5.6 Hz), 5.00 (d, 2H,
J ) 2.6 Hz), 7.24∼7.33 (m, 4H)
1.23∼1.33 (m, 12H), 1.43∼1.48 (m, 2H), 1.61∼1.66 (m, 2H), 1.80∼1.89 (m, 2H), 2.11∼2.16 (m, 1H), 2.23∼2.37 (m, 5H), 4.06∼4.14 (m, 2H),
5.18∼5.20 (m, 2H), 6.96∼7.03 (m, 1H), 7.17∼7.27 (m, 2H)
Table 3. Fungicidal Activity of Compounds 7 against Rhizoctonia solani
Kühna
Table 4. Fungicidal Spectrum of 7B3 (a mixture of Z and E isomers)
pathogen
EC50 (µg/mL)
compds
No.
EC50
compds
No.
EC50
compds
No.
EC50
pear black spot (Alternaria kikuchiana)
1.2
1.9
4.6
8.6
12.0
13.8
19.3
23.9
29.0
33.3
44.2
53.1
57.8
(µg/mL)
(µg/mL)
(µg/mL)
tomoto southern blight (Phyllospicpa physaleos Sacc)
cotton rhizoctonia rot (Rhizoctonia solani Kühn)
cucumber gray mold (Botrytis cinerea Pers)
asparagus stem blight (Phomopsis asparagi Sacc)
apple ring spot (Physalospora piricola Nose)
cotton verticillium wilt (Vercicillium alboatrum Reinke et Berthold)
cucumber anthracnose (Colletotrichum Lagenarium)
cotton fusarium wilt (Fusarium vasinfectum Atkimson)
cotton damping-off (Pythium aphanibermatum (Eds.) Fipzp)
tomoto early blight (Alternaria solani Jones et Grout)
tomoto leaf mold (Cladosporium fulvum Cooke)
peppers fruit rot (Phytophthora capsici Len)
7A–1(1)
7A–1(2)
7A-2(2)
51.34
55.80
25.84
22.10
9.11
44.03
21.76
55.10
7.21
7B–2(2)
7B–3(1)
7B–3(2)
7B–4(1)
7B–4(2)
7B–5(1)
7B–5(2)
22.73
13.14
3.62
45.61
15.92
3.97
7A–3(1)
7A–3(2)
7A–4(1)
7A–4(2)
7A–5(1)
7A–5(2)
7A–6(1)
7A–6(2)
7A–7(1)
7A–7(2)
7A–8(1)
7A–8(2)
7A–9(1)
7A–9(2)
7A–10(1)
7A–10(2)
7A–11(1)
7A–11(2)
7A–12(1)
7A-12(2)
7A–13(1)
7A–13(2)
7A–14(1)
7A-14(2)
7A–15(1)
7A–15(2)
7A–16(1)
7A-16(2)
7A–17(1)
7A–17(2)
carbendazim
7C–3
7C–4
7C–5
8.08
12.76
13.36
2.34
48.40
30.38
209.43
50.35
101.13
69.12
135.04
127.22
18.15
7.24
111.31
50.55
74.91
12.07
97.25
84.79
49.32
166.33
1734.74
42.99
100.00
105.66
56.43
52.55
1.54
7B–7(1)
7B–7(2)
19.25
27.88
7C–7
9.68
In conclusion, all of above results confirmed our original
judgment: macrocyclic compounds with two polarizable groups
on the ring may have certain fungicidal activity. In this research,
all of tetradecanlactam and pentadecanlactam derivatives,
containing two polarizable groups –CONH- and )N-O- on
the ring (7A and 7B), and pentadecanlactone derivatives,
containing –COO- and )N-O- on the ring (7C), displayed
fair to excellent fungicidal activity against Rhizoctonia solani
Kühn. In the macrocyclic derivatives with two polarizable
groups on the ring, the compounds in which there is a three
methylene distance (CH2CH2CH2) between the two polarizable
groups (7B and 7C) are more active than those in which there
is a two-methylene distance (CH2CH2) between the two polariz-
able groups (7A). The fact that compounds 7B have higher
fungicidal activity than compounds 7C indicates that the
macrocyclic derivatives with a hydrogen-bonding acceptor (here,
it is )N-O-) and a hydrogen-bonding donor (here, it is
-CONH-) have the best fungicidal activity among the mac-
rocyclic derivatives with two polarizable groups and a three
methylenes distance between these groups. The information can
be very useful for designing new macrocyclic fungicides. The
7B–9(1)
7B–9(2)
7B10(1)
7B10(2)
47.75
51.48
5.84
7C–9
40.39
45.13
7C–10
8.28
7B–13(1)
7B–13(2)
68.37
164.28
7C-13
7C–15
19.61
51.27
7B-15(1)
7B-15(2)
2.34
6.21
a Regression equations and correlation coefficients are omitted.
comparable with the commercial fungicide carbendazin (with
EC50 ) 1.54 µg/mL). The pentadecanlactone derivatives (7C)
have somewhat improved fungicidal activity against Rhizoc-
tonia solani Kühn than that of 7A but are less active than
7B. Namely, in the order of 7A, 7C, and 7B, the compounds
have a gradual increase of fungicidal activity. It can be seen
from Table 4 that compound 7B3 has a broad spectrum of
fungicidal activities and has especially excellent fungicidal
activities against Alternaria kikuchiana and Phyllospicpa
physaleos Sacc.The EC50 values were 1.2 and 1.9 µg/mL,
respectively.
Figure 2. Z and E Isomers of Compounds 7A (n ) 0) and 7B
(n ) 1).

Synthesis and Fungicidal Activity of Macrolactams and Macrolactones
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Received for review September 13, 2007. Revised manuscript received
October 30, 2007. Accepted October 30, 2007. We acknowledge financial
support of this investigation by the National Basic Research Program
of China (2003CB114407).
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