Synthesis and antifeeding activities of tonghaosu analogues

Article abstract of DOI:10.1021/jf049479v

Tonghaosu (1), a lead for a botanical antifeedant, and its 22 analogues were synthesized according to a previously reported concise and straightforward procedure. The structures of all new compounds were confirmed by NMR, IR, MS, and HREIMS or elemental analysis. Their insect antifeedant activities against the large white butterfly (Pieris brassicae L.) were examined, and six analogues (Z- and E-6h and Z-isomers of 6i-I), which contain 1,3-diyn or 3,4-methylenedioxyphenyl acetylene group, showed considerable antifeedant activity. Interestingly, Z-isomers of 6i-k are much more active than their corresponding E-isomers.

Full text of DOI:10.1021/jf049479v

J. Agric. Food Chem. 2004, 52, 6719−6723 6719
Synthesis and Antifeeding Activities of Tonghaosu Analogues
LI CHEN,† HAN-HONG XU,§ BIAO-LIN YIN,† CHUN XIAO,# TAI-SHAN HU,† AND
YU-LIN WU*,†
State Key Laboratory of Bio-organic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China; Laboratory of
Insect Toxicology, South China Agricultural University, Guangzhou, Guangdong 510642, China; and
College of Plant Protection, Yunnan Agricultural University, Kunming, Yunnan 650201, China
Tonghaosu (1), a lead for a botanical antifeedant, and its 22 analogues were synthesized according
to a previously reported concise and straightforward procedure. The structures of all new compounds
were confirmed by NMR, IR, MS, and HREIMS or elemental analysis. Their insect antifeedant activities
against the large white butterfly (Pieris brassicae L.) were examined, and six analogues (Z- and
E-6h and Z-isomers of 6i-l), which contain 1,3-diyn or 3,4-methylenedioxyphenyl acetylene group,
showed considerable antifeedant activity. Interestingly, Z-isomers of 6i-k are much more active than
their corresponding E-isomers.
KEYWORDS: Tonghaosu; spiroketal; antifeedant; Pieris brassicae
INTRODUCTION
Tonghaosu, 2-(2′,4′-hexadiynylidene)-1,6-dioxaspiro[4,4]-
non-3-ene (1), is an antifeedant component of the Chinese
vegetable tonghao (Chrysanthemum segetum L. or Chrysanthe-
mum coronarium L.) (1) and was also found in other plants of
tribe Anthemideae of the Compositae (2-4). In our previous
studies in the search for new insecticidal compounds against
vegetable pests, tonghaosu and a variety of its analogues (2)
(5-9) were prepared via a convenient method established by
us, and the bioactivities of some analogues were evaluated (10-
15). Preliminary results indicated (11-15) analogues with 2′-
nitrophenyl or a pyridinyl group at C10 (see compound 1 in
Figure 1 for numbering) had appreciable antifeeding activity.
In view of the fact that many other acetylene-containing
natural products (16-20) as well as synthetic compounds (21)
showed good insect antifeeding activities, we focused on the
synthesis of new series of tonghaosu analogues, which would
contain an acetylene function and also varied B-rings. Herein,
we report recent progress along this line and the antifeeding
activities of these newly prepared tonghaosu analogues against
the large white butterfly (Pieris brassicae L.).
Figure 1. Tonghaosu (1) and its analogues.
Insect Rearing. The larvae of the large white butterfly (P. brassicae
L.) were collected from suburban vegetable fields of Kunming, Yunnan
Province, China, and reared with cabbage (Brassica oleracea L.)
seedling in an environmental chamber held at 25 ( 1 °C under a
photoperiod of 14:10 h (light/dark). Larvae of the second generation
were reared to third instar for a feeding test.
Evaluation of Test Compounds with Leaf Disk Bioassay. Anti-
feeding activity was assayed according to the conventional leaf-disk
method (22). The test compounds were dissolved in acetone at a
concentration of 1000 µg/mL. Leaf disks (d ) 1.25 cm) of cabbage
were dipped into the prepared solutions for 1 s according to the method
of Yee et al. (23), and control disks were dipped into acetone. These
treated disks were allowed to stand on a plate to evaporate the acetone.
Three disks and two larvae were placed in a wet filter paper disk in a
9.0 cm diameter Petri dish, with five replicates of each concentration.
Remaining uneaten leaf areas were measured using an LI-COR 3000
leaf area meter (LI-COR, Lincoln, NE) 48 h after treatment. Ten
randomly chosen leaf disks dipped in acetone and unexposed to larvae
were used to determine the leaf areas consumed. The antifeeding
percentage was calculated as
MATERIALS AND METHODS
Chemistry. IR spectra were recorded on Perkin-Elmer 983 or
1
Shimadzu IR-440 spectrometers. H and 13C NMR were recorded in
CDCl3 on an AMX-300, DPX-300, or DRX-400 spectrometer with
TMS as the internal standard. Mass spectra were taken on a Mariner,
HP5973N, or HP5989A instrument. Flash column chromatography was
performed on silica gel H (10-40 µm) with a petroleum ether/ethyl
acetate system as eluent.
antifeedancy ) (CK - T)/CK × 100%
where CK and T are control disk areas eaten and treated disk areas
eaten, respectively.
The further feeding test of active compounds (azadirachtin as
standard control) was carried out at a serial concentrations to obtain
antifeeding percentages of 20-90%. The 50% antifeeding concentration
(AFC50) was determined by regression analysis (24). AFC50 values were
considered to be significantly different if their 95% confidence limit
(CL) did not overlap.
* Author to whom correspondence should be addressed (fax +86 21
641 66128; e-mail ylwu@mail.sioc.ac.cn).
† Chinese Academy Sciences.
§ South China Agricultural University.
# Yunnan Agricultural University.
10.1021/jf049479v CCC: $27.50
© 2004 American Chemical Society
Published on Web 10/07/2004

6720 J. Agric. Food Chem., Vol. 52, No. 22, 2004
Chen et al.
Preparation of Test Compounds. 1,1-Dibromo-2-(3,4-methylene-
dioxyphenyl)ethylene (2d). Carbon tetrabromide (33.16 g, 100 mmol)
in CH2Cl2 (60 mL) was added to a stirred solution of triphenylphosphine
(26.2 g, 100 mmol) in CH2Cl2 (200 mL) under N2 at 0 °C. After 10
min, zinc dust (6.5 g, 100 mmol) was added, and the orange suspension
was stirred for 2 h at room temperature. To this mixture was added at
0 °C piperonal (7.5 g, 50 mmol) dissolved in CH2Cl2 (30 mL), and the
reaction mixture was stirred for 16 h at room temperature. The resulting
precipitate was filtered off and the filtrate concentrated in vacuo. The
residue was chromatographed on silica gel column (petroleum ether/
ethyl acetate 10:1) to provide the title compound (13.16 g, 86%) as a
colorless oil: 1H NMR (CDCl3, 300 MHz) δ 7.37 (1H, s), 7.19 (1H, d,
J ) 1.2 Hz), 6.95 (1H, dd, J ) 1.5, 8.1 Hz), 6.80 (1H, d, J ) 8.4 Hz),
5.99 (2H, s).
Acetic acid 3-[5-(3-benzo[1,3]dioxol-5-yl-1-hydroxyprop-2-ynyl)-
furan-2-yl]propyl ester (4j) was obtained as a yellow oil (yield, 91%)
according to a procedure similar to that used for 4i: 1H NMR (CDCl3,
300 MHz) δ 7.00 (1H, dd, J ) 1.8, 7.8 Hz), 6.92 (1H, d, J ) 1.2 Hz),
6.76 (1H, d, J ) 7.8 Hz), 6.40 (1H, d, J ) 3.6 Hz), 6.00 (1H, d, J )
3.3 Hz), 5.98 (2H, s), 5.61 (1H, s), 4.12 (2H, t, J ) 6.4 Hz), 2.73 (2H,
t, J ) 7.5 Hz), 2.62 (1H, br s, -OH), 2.06 (3H, s), 1.95-2.05 (2H,
m).
Acetic acid 4-[5-(3-benzo[1,3]dioxol-5-yl-1-hydroxyprop-2-ynyl)-
furan-2-yl]butyl ester (4k) was obtained as a brown oil (yield, 72%)
according to a procedure similar to that used for 4i: 1H NMR (CDCl3,
300 MHz) δ 7.00 (1H, dd, J ) 1.8, 8.1 Hz), 6.91 (1H, t, J ) 1.5 Hz),
6.76 (1H, dd, J ) 2.1, 8.1 Hz), 6.39 (1H, d, J ) 2.4 Hz), 5.98 (1H, s),
5.97 (2H, s), 5.61 (1H, s), 4.07 (2H, t, J ) 5.8 Hz), 2.96 (1H, br s,
-OH), 2.67 (2H, t, J ) 6.6 Hz), 2.04 (3H, d, J ) 2.4 Hz), 1.71 (4H,
m).
Typical Procedure for the Synthesis of 4a-h. Acetic Acid 3-[5-(1-
Hydroxyhept-2-ynyl)furan-2-yl]propyl Ester (4a). To a solution of
1-hexyne (1.64 g, 20 mmol) and TMEDA (2.56 g, 22 mmol) in 20 mL
of dry THF at -78 °C under nitrogen was added n-butyllithium (1.6
M, 12.5 mL, 20 mmol) via syringe over a period of 10 min. The reaction
mixture was stirred for 30 min at -78 °C, warmed to room temperature,
and then added dropwise to a solution of 5-(3-acetoxypropyl)-2-
furaldehyde (3.92 g, 20 mmol) in 20 mL of dry THF at -78 °C. Stirring
was continued at -78 °C for 1 h, after which time the cooling bath
was removed and the reaction mixture was stirred for an additional 2
h at room temperature. The reaction was quenched with saturated
aqueous NH4Cl (10 mL), the organic layer was separated, and the
aqueous layer was extracted with ethyl acetate (50 mL × 3). The
combined organic layers were washed with saturated brine, dried over
Na2SO4, and concentrated in vacuo. Purification of the residue by
column chromatography on silica gel (petroleum ether/ethyl acetate
5:1) yielded acetic ester 4a (4.89 g, 88%) as a pale yellow oil: 1H
NMR (CDCl3, 300 MHz) δ 6.33 (1H, d, J ) 3.0 Hz), 5.98 (1H, d, J )
3.0 Hz), 5.40 (1H, s), 4.12 (2H, t, J ) 6.6 Hz), 2.72 (2H, t, J ) 7.5
Hz), 2.61 (1H, br s, -OH), 2.28 (2H, td, J ) 2.1, 6.9 Hz), 2.07 (3H,
s), 2.00 (2H, m), 1.48 (4H, m), 0.93 (3H, t, J ) 7.3 Hz).
Acetic acid 2-[5-(3-benzo[1,3]dioxol-5-yl-1-hydroxyprop-2-ynyl)-
furan-2-ylmethoxy]ethyl ester (4l) was obtained as a brown oil (yield,
57%) according to a procedure similar to that used for 4i: 1H NMR
(CDCl3, 300 MHz) δ 7.01 (1H, dd, J ) 1.8, 8.4 Hz), 6.91 (1H, d, J )
1.5 Hz), 6.77 (1H, d, J ) 7.8 Hz), 6.47 (1H, d, J ) 3.3 Hz), 6.32 (1H,
d, J ) 3.3 Hz), 5.98 (2H, s), 5.64 (1H, s), 4.51 (2H, d, J ) 1.5 Hz),
4.22 (2H, t, J ) 4.9 Hz), 3.71 (2H, t, J ) 4.6 Hz), 2.96 (1H, br s,
-OH), 2.08 (3H, s).
Typical Procedure for the Synthesis of 5. 1-[5-(3-Hydroxypropyl)-
furan-2-yl]hept-2-yn-1-ol (5a). Potassium carbonate (1.0 g) was added
to a solution of furanmethanol (1.455 g, 5.23 mmol) in methanol (20
mL) and H2O (2 mL) and stirred for 6 h for deacetylation. Methanol
was evaporated, and the resultant mixture was extracted with ethyl
acetate. The organic phase was washed with saturated brine, dried over
Na2SO4, and concentrated in vacuo. The residue was purified by flash
chromatography (petroleum ether/ethyl acetate 2:1 + 1% v/v triethyl-
amine) to give the title compound (1.074 g, 87%) as a brown oil: 1H
NMR (CDCl3, 300 MHz) δ 6.33 (1H, d, J ) 3.0 Hz), 5.97 (1H, d, J )
3.3 Hz), 5.40 (1H, s), 3.69 (2H, t, J ) 6.3 Hz), 2.73 (2H, t, J ) 7.2
Hz), 2.67 (1H, br s, -OH), 2.27 (2H, td, J ) 2.1, 7.2 Hz), 1.90 (2H,
m), 1.77 (1H, br s, -OH), 1.48 (4H, m), 0.92 (3H, t, J ) 7.2 Hz); IR
Vmax 3347, 2958, 2935, 2874, 2231, 1665, 1558, 1432 cm-1; EIMS,
m/z (%) 236 (M+, 21.4), 219 (26.5), 187 (83.2), 177 (27.9), 147 (16.6),
131 (32.4), 107 (43.8), 91 (100), 77 (51.5), 55 (49.3), 41 (66.1).
HREIMS for C14H20O3: calcd 236.1412, found 236.1423.
Acetic acid 4-[5-(1-hydroxyhept-2-ynyl)furan-2-yl]butyl ester (4b)
was obtained as a brown oil (yield, 95%) according to the typical
procedure for 4a: 1H NMR (CDCl3, 300 MHz) δ 6.32 (1H, d, J ) 3.3
Hz), 5.95 (1H, d, J ) 3.0 Hz), 5.39 (1H, s), 4.07 (2H, t, J ) 6.1 Hz),
2.65 (2H, t, J ) 6.7 Hz), 2.42 (1H, br s, -OH), 2.27 (2H, td, J ) 2.2,
6.6 Hz), 2.05 (3H, s), 1.70 (4H, m), 1.48 (4H, m), 0.92 (3H, t, J ) 7.2
Hz).
1-[5-(4-Hydroxybutyl)furan-2-yl]hept-2-yn-1-ol (5b) was obtained
as a brown oil (yield, 98%) according to the procedure for 5a: 1H
NMR (CDCl3, 300 MHz) δ 6.29 (1H, d, J ) 3.0 Hz), 5.92 (1H, dd, J
) 0.7, 3.1 Hz), 5.37 (1H, s), 3.60 (2H, t, J ) 6.1 Hz), 2.91 (1H, br s,
-OH), 2.65 (2H, t, J ) 7.3 Hz), 2.27 (2H, td, J ) 1.7, 6.9 Hz), 2.01
(1H, br s, OH), 1.37-1.77 (8H, m), 1.26 (1H, br s, OH), 0.93 (3H, t,
J ) 7.6 Hz); IR Vmax 3352, 2957, 2935, 2873, 2231, 1609, 1558, 1510,
1459, 1432 cm-1; EIMS, m/z (%) 249 (M+ - 1, 2.7), 190 (17.5), 177
(8.9), 161 (8.7), 146 (14.7), 131 (15.0), 107 (18.6), 91 (23.2), 81 (21.0),
55 (23.3), 41 (27.8). HREIMS for C15H20O2 (M+ - H2O): calcd
232.1463, found 232.1469.
Acetic acid 2-[5-(1-hydroxyhept-2-ynyl)furan-2-ylmethoxy]ethyl ester
(4c) was obtained as a brown oil (yield, 87%) according to the typical
procedure for 4a: 1H NMR (CDCl3, 300 MHz) δ 6.41 (1H, d, J ) 3.0
Hz), 6.30 (1H, d, J ) 3.3 Hz), 5.44 (1H, s), 4.50 (2H, d, J ) 1.8 Hz),
4.22 (2H, t, J ) 4.8 Hz), 3.69 (2H, t, J ) 4.8 Hz), 2.66 (1H, br s,
-OH), 2.27 (2H, td, J ) 1.9, 7.2 Hz), 2.09 (3H, s), 1.48 (4H, m), 0.92
(3H, t, J ) 7.2 Hz).
4d, 4g, and 4f are known compounds reported in ref 6.
Acetic acid 4-[5-(1-hydroxy-3-phenylprop-2-ynyl)furan-2-yl]butyl
ester (4e) was obtained as a yellow oil (yield, 87%) according to the
typical procedure for 4a: 1H NMR (CDCl3, 300 MHz) δ 7.48 (2H,
m), 7.34 (3H, m), 6.42 (1H, d, J ) 3.0 Hz), 5.98 (1H, d, J ) 3.0 Hz),
5.64 (1H, d, J ) 6.0 Hz), 4.07 (2H, t, J ) 6.4 Hz), 2.68 (2H, t, J ) 6.9
Hz), 2.54 (1H, d, J ) 7.2 Hz, -OH), 2.04 (3H, s), 1.68-1.75 (4H, m).
Acetic acid 2-[5-(1-hydroxy-3-phenylprop-2-ynyl)furan-2-ylmethoxy]-
ethyl ester (4f) was obtained as a yellow oil (yield, 92%) according to
the typical procedure for 4a: 1H NMR (CDCl3, 300 MHz) δ 7.48 (2H,
m), 7.31 (3H, m), 6.50 (1H, d, J ) 3.0 Hz), 6.33 (1H, d, J ) 3.0 Hz),
5.68 (1H, s), 4.52 (2H, d, J ) 1.2 Hz), 4.22 (2H, t, J ) 4.8 Hz), 3.71
(2H, t, J ) 4.8 Hz), 2.08 (3H, s).
Acetic acid 2-[5-(1-hydroxyhexa-2,4-diynyl)furan-2-ylmethoxy]ethyl
ester (4i; general procedure for 4j-l) was obtained as a yellow oil in
a manner similar to the synthesis of 4a except for treatment of 1,1-
dibromide 2c with 2 equiv of n-butyllithium instead of 1 equiv of
n-butyllithium (yield, 60%): 1H NMR (CDCl3, 300 MHz) δ 6.41 (d, J
) 3.6 Hz, 1H), 6.30 (d, J ) 3.0 Hz, 1H), 5.47 (d, J ) 4.5 Hz, 1H),
4.49 (s, 2H), 4.21 (dd, J ) 3.9, 5.4 Hz, 2H), 3.69 (dd, J ) 4.0, 5.2 Hz,
2H), 2.90 (br s, 1H, -OH), 2.08 (s, 3H), 1.96 (d, J ) 1.5 Hz, 3H).
1-[5-(2-Hydroxyethoxymethyl)furan-2-yl]hept-2-yn-1-ol (5c) was
obtained as a brown oil (yield, 93%) according to the procedure for
5a: 1H NMR (CDCl3, 300 MHz) δ 6.38 (1H, d, J ) 3.6 Hz), 6.28
(1H, d, J ) 3.0 Hz), 5.41 (1H, s), 4.48 (2H, s), 3.70 (2H, t, J ) 4.3
Hz), 3.58 (2H, t, J ) 4.5 Hz), 2.78 (1H, br s, -OH), 2.34 (1H, br s,
-OH), 2.26 (2H, td, J ) 2.0, 7.2 Hz), 1.46 (4H, m), 0.91 (3H, t, J )
7.2 Hz); IR Vmax 3370, 2959, 2873, 2287, 2231, 1602 cm-1; EIMS, m/z
(%) 252 (M+, 20.8), 234 (35.0), 190 (60.9), 177 (100.0). HREIMS for
C14H20O4: calcd 252.1361, found 252.1355.
4-[5-(1-Hydroxy-3-phenylprop-2-ynyl)furan-2-yl]butan-1-ol (5e) was
obtained as a brown oil (yield, 96%) according to the procedure for
5a: 1H NMR (CDCl3, 300 MHz) δ 7.47 (2H, m), 7.32 (3H, m), 6.40
(1H, d, J ) 3.0 Hz), 5.97 (1H, d, J ) 3.3 Hz), 5.63 (1H, s), 3.64 (2H,
t, J ) 6.4 Hz), 3.08 (1H, br s, -OH), 2.66 (2H, t, J ) 7.3 Hz), 1.57-
1.78 (4H, m), 1.79 (1H, br s, -OH); IR Vmax 3341, 2941, 2868, 2229,
1600, 1558, 1491, 1457, 1444 cm-1; EIMS, m/z (%) 270 (M+, 3.0),
252 (41.9), 197 (25.4), 165 (20.5), 129 (27.9), 86 (100), 58 (21.1), 43
(22.4). HREIMS for C17H18O3: calcd 270.1256, found 270.1256.

Antifeeding Activities of Tonghaosu Analogues
J. Agric. Food Chem., Vol. 52, No. 22, 2004 6721
1-[5-(2-Hydroxyethoxymethyl)furan-2-yl]-3-phenylprop-2-yn-1-ol (5f)
was obtained as a brown oil (yield, 97%) according to the procedure
for 5a: 1H NMR (CDCl3, 300 MHz) δ 7.46 (2H, m), 7.31 (3H, m),
6.47 (1H, d, J ) 3.0 Hz), 6.30 (1H, d, J ) 3.0 Hz), 5.66 (1H, s), 4.49
(2H, s), 3.71 (2H, t, J ) 4.8 Hz), 3.60 (2H, m), 3.36 (1H, br s, -OH),
2.45 (1H, br s, -OH); IR Vmax 3363, 2933, 2869, 2231, 1733, 1653,
1599, 1558, 1491, 1444 cm-1. HREIMS for C14H20O4: calcd 252.1361,
found 252.1355.
1-[5-(2-Hydroxyethoxymethyl)furan-2-yl]hexa-2,4-diyn-1-ol (5i) was
obtained as a brown oil (yield, 96%) according to the procedure for
5a: 1H NMR (CDCl3, 300 MHz) δ 6.41 (1H, d, J ) 3.6 Hz), 6.29
(1H, d, J ) 3.0 Hz), 5.46 (1H, s), 4.49 (2H, br s), 3.72 (2H, t, J ) 4.3
Hz), 3.60 (2H, t, J ) 4.5 Hz), 3.26 (1H, br s, OH), 2.45 (1H, br s,
OH), 1.96 (s, 3H); IR Vmax 3349, 2916, 2730, 2260, 1653, 1105, 1065,
1015 cm-1; EIMS, m/z (%) 234 (M+, 6.7), 217 (10.9), 189 (10.6), 172
(52.2), 143 (100), 115 (46.7), 91 (62.5), 77 (24.4).
35.52, 31.02, 24.47, 21.91, 19.31, 13.57; IR Vmax 2959, 2934, 1639,
1581, 1458, 1344, 1224 cm-1; EIMS, m/z (%) 218 (M+, 100), 189
(13.8), 176 (65.0), 161 (51.2), 147 (61.5), 133 (74.7), 105 (42.5), 91
(56.0), 77 (50.6), 55 (55.9). HREIMS for C13H12O3: calcd 218.1307,
found 218.1258.
2-Hept-2-ynylidene-1,6-dioxa-spiro[4.5]dec-3-ene (6b) was obtained
as a yellow oil (yield, 69%) according to the procedure for 6a.
Z-isomer: 1H NMR (CDCl3, 300 MHz) δ 6.20 (1H, d, J ) 5.7 Hz),
6.08 (1H, d, J ) 5.7 Hz), 4.57 (1H, t, J ) 2.4 Hz), 4.12 (1H, td, J )
1.0, 11.4 Hz), 3.83 (1H, dt, J ) 2.3, 11.2 Hz), 2.40 (2H, m), 1.49-
1.81 (10H, m), 0.94 (3H, td, J ) 2.6, 7.2 Hz); 13C NMR (CDCl3, 75
MHz) δ 164.51, 135.93, 126.76, 111.97, 95.01, 80.35, 76.01, 63.95,
32.71, 30.91, 24.58, 21.77, 19.57, 19.21, 13.58; IR Vmax 3093, 3049,
2955, 2873, 1773, 1645, 1586, 1467, 1441, 1232 cm-1; EIMS, m/z
(%) 232 (M+, 100), 189 (26.9), 175 (29.6), 161 (33.6), 147 (55.5), 133
(24.8), 105 (15.5), 91 (18.6), 77 (18.1), 55 (19.3). HREIMS for
C15H20O2: calcd 232.1463, found 232.1462. E-isomer: 1H NMR
(CDCl3, 300 MHz) δ 6.63 (1H, dd, J ) 0.6, 5.7 Hz), 6.13 (1H, dd, J
) 2.1, 5.7 Hz), 4.95 (1H, m), 3.99 (1H, td, J ) 3.6, 11.4 Hz), 3.82
(1H, m), 2.32 (2H, td, J ) 2.4, 6.9 Hz), 1.38-1.81 (10H, m), 0.92
(3H, t, J ) 6.0 Hz); 13C NMR (CDCl3, 75 MHz) δ 165.98, 125.17,
136.49, 111.88, 91.68, 81.23, 76.30, 63.99, 31.07, 32.65, 24.47, 21.91,
19.33, 19.25, 13.54; IR Vmax 2958, 2874, 1639, 1583, 1220 cm-1; EIMS,
m/z (%) 232 (M+, 100), 189 (25.5), 175 (27.8), 161 (31.2), 147 (57.0),
133 (21.8), 105 (13.6), 91 (15.6), 77 (14.9), 55 (14.0). HREIMS for
C15H20O2: calcd 232.1463, found 232.1511.
2-Hept-2-ynylidene-1,6,9-trioxaspiro[4.5]dec-3-ene (6c) was ob-
tained as a yellow oil (yield, 62%) according to the procedure for 6a.
Z-isomer: 1H NMR (CDCl3, 300 MHz) δ 6.33 (1H, d, J ) 5.7 Hz),
6.04 (1H, dd, J ) 0.9, 5.7 Hz), 4.67 (1H, t, J ) 1.9 Hz), 4.35 (1H, td,
J ) 3.1, 10.5 Hz), 3.69-3.88 (5H, m), 2.39 (2H, td, J ) 2.4, 6.9 Hz),
1.51 (4H, m), 0.93 (3H, t, J ) 7.2 Hz); IR Vmax 3095, 3048, 2960,
2934, 2874, 2860, 2780, 2210, 1646, 1585, 1455, 1432 cm-1; EIMS,
m/z (%) 234 (M+, 100), 191 (17.4), 177 (35.8), 139 (28.9), 107 (16.3),
91 (19.3), 77 (18.0), 55 (11.6). HREIMS for C14H18O3: calcd 234.1256,
found 234.1259. Anal. Calcd for C14H18O3: C, 71.77; H, 7.74. Found:
C, 71.68; H 7.86. E-isomer: 1H NMR (CDCl3, 300 MHz) δ 6.76 (1H,
dd, J ) 0.7, 5.5 Hz), 6.06 (1H, dd, J ) 1.8, 5.7 Hz), 5.08 (1H, m),
4.26 (1H, m), 3.66-3.86 (5H, m), 2.32 (2H, td, J ) 2.4, 7.2 Hz), 1.49
(4H, m), 0.91 (3H, t, J ) 7.2 Hz); IR Vmax 2961, 2934, 2859, 1639,
1581, 1456, 1213 cm-1; EIMS, m/z (%) 234 (M+, 100), 191 (22.3),
177 (57.2), 139 (53.3), 105 (46.8), 91 (70.9), 77 (80.1), 55 (62.7).
HREIMS for C14H18O3: calcd 234.1256, found 234.1256.
3-Benzo[1,3]dioxol-5-yl-1-[5-(3-hydroxypropyl)furan-2-yl]propy-
nol (5j) was obtained as a brown oil (yield, 98%) according to the
procedure for 5a: 1H NMR (CDCl3, 300 MHz) δ 7.00 (1H, dd, J )
1.5, 8.1 Hz), 6.91 (1H, d, J ) 1.5 Hz), 6.76 (1H, d, J ) 8.1 Hz), 6.39
(1H, d, J ) 3.0 Hz), 5.99 (1H, d, J ) 3.3 Hz), 5.98 (2H, s), 5.60 (1H,
s), 3.70 (2H, t, J ) 6.3 Hz), 2.75 (2H, t, J ) 7.3 Hz), 1.92 (2H, m); IR
Vmax 3350, 2942, 2900, 2231, 1734, 1604, 1558, 1504, 1490, 1443,
1249, 1211 cm-1; EIMS, m/z (%) 300 (M+, 38.7), 283 (13.0), 265 (8.9),
251 (12.0), 238 (9.7), 173 (14.0), 101 (19.3), 86 (100), 58 (28.2), 43
(31.3). HREIMS for C17H16O5: calcd 300.0998, found 300.0999.
4-[5-(3-Benzo[1,3]dioxol-5-yl-1-hydroxyprop-2-ynyl)furan-2-yl]bu-
tan-1-ol (5k) was obtained as a brown oil (yield, 82%) according to
the procedure for 5a: 1H NMR (CDCl3, 300 MHz) δ 6.99 (1H, dd, J
) 1.6, 8.2 Hz), 6.91 (1H, d, J ) 1.5 Hz), 6.75 (1H, d, J ) 7.8 Hz),
6.38 (1H, d, J ) 3.0 Hz), 5.97 (2H, s), 5.96 (1H, d, J ) 4.2 Hz), 5.60
(1H, s), 3.63 (2H, t, J ) 6.3 Hz), 2.65 (2H, t, J ) 7.4 Hz), 1.68 (4H,
m); IR Vmax 3387, 3206, 2949, 2901, 2867, 2685, 2228, 2195, 1856,
1604, 1557, 1504, 1490, 1480, 1441, 1412, 1248, 1212, 1194 cm-1
;
EIMS, m/z (%) 314 (M+, 21.5), 296 (100), 267 (13.4), 251 (27.0), 238
(34.4), 149 (30.6), 126 (15.6), 74 (14.2), 55 (19.1). HREIMS for
C18H16O4 (M+ - H2O): calcd 296.1049, found 296.1047.
3-Benzo[1,3]dioxol-5-yl-1-[5-(2-hydroxyethoxymethyl)furan-2-yl]-
prop-2-yn-1-ol (5l) was obtained as a brown oil (yield, 91%) according
to the procedure for 5a: 1H NMR (CDCl3, 300 MHz) δ 7.00 (1H, dd,
J ) 1.5, 8.1 Hz), 6.91 (1H, d, J ) 1.5 Hz), 6.75 (1H, d, J ) 7.8 Hz),
6.45 (1H, d, J ) 3.3 Hz), 6.31 (1H, d, J ) 3.3 Hz), 5.98 (2H, s), 5.64
(1H, s), 4.50 (2H, s), 3.73 (2H, t, J ) 4.2 Hz), 3.61 (2H, t, J ) 4.6
Hz); IR Vmax 3368, 2901, 2230, 1733, 1604, 1555, 1504, 1490, 1443,
1250, 1212 cm-1; EIMS, m/z (%) 316 (M+, 43.5), 298 (18.2), 241
(44.8), 197 (44.0), 181 (32.2), 173 (33.4), 129 (43.5), 86 (100), 58
(28.1), 43 (35.1). HREIMS for C17H16O6: calcd 316.0947, found
316.0942.
2-(3-Phenyl-2-butynyliden)-1,6-dioxaspiro[4,5]dec-3-ene (6e) was
obtained as a pale yellow oil (yield, 94%) according to the procedure
for 6a. Z-isomer: 1H NMR (CDCl3, 300 MHz) δ 7.46 (2H, m), 7.30
(3H, m), 6.28 (1H, d, J ) 5.7 Hz), 6.18 (1H, d, J ) 5.7 Hz), 4.82 (1H,
s), 4.16 (1H, m), 3.86 (1H, m), 1.62-1.85 (6H, m); IR Vmax 3095, 3053,
2948, 2881, 2193, 1639, 1595, 1587, 1489, 1469, 1442, 1227 cm-1
;
Typical Procedure for the Synthesis of 6. 2-Hept-2-ynylidene-1,6-
dioxaspiro[4.4]non-3-ene (6a). To a solution of furandiol (1.18 g, 5
mmol) in 20 mL of toluene was added 1.5 g of CuSO4‚5H2O (6 mmol).
The reaction mixture was stirred at 90 °C over 6 h until the starting
material disappeared according to TLC and the copper salts were
filtered. The filtrate was concentrated in vacuo, and the residue was
carefully chromatographed (silica gel, petroleum ether/ethyl acetate 20:1
+ 0.5% triethylamine) to give the title compound (Z-isomer, 328 mg;
E-isomer, 566 mg, 82%) as a yellow oil. Z-isomer: 1H NMR (CDCl3,
300 MHz) δ 6.22 (1H, d, J ) 5.7 Hz), 6.04 (1H, dd, J ) 0.7, 5.5 Hz),
4.57 (1H, td, J ) 0.6, 1.8 Hz), 4.23 (1H, m), 3.97 (1H, m), 2.37 (2H,
td, J ) 2.4, 6.9 Hz), 2.26 (2H, m), 2.04 (2H, m), 1.52 (4H, m), 0.91
(3H, t, J ) 7.2 Hz); 13C NMR (CDCl3, 75 MHz) δ 163.40, 127.58,
133.25, 120.39, 95.24, 80.41, 75.79, 69.26, 35.61, 30.89, 24.50, 21.88,
19.66, 13.58; IR Vmax 3094, 3047, 2959, 2874, 1645, 1586, 1458, 1345,
1240 cm-1; EIMS, m/z (%) 218 (M+, 100), 189 (12.1), 176 (51.8),
161 (38.7), 147 (55.0), 133 (50.0), 105 (23.3), 91 (31.2), 77 (20.9), 55
(18.5). HREIMS for C13H12O3: calcd 218.1307, found 218.1322.
E-isomer: 1H NMR (CDCl3, 300 MHz) δ 6.68 (1H, d, J ) 5.7 Hz),
6.11 (1H, dd, J ) 1.9, 4.9 Hz), 4.92 (1H, dd, J ) 2.2, 4.3 Hz), 4.18
(1H, m), 3.97 (1H, m), 2.33 (2H, td, J ) 2.4, 6.6 Hz), 1.97-2.28 (4H,
m), 1.46 (4H, m), 0.92 (3H, t, J ) 7.2 Hz); 13C NMR (CDCl3, 75
MHz) δ 165.06, 125.95, 133.88, 120.17, 91.82, 81.30, 76.15, 69.26,
EIMS, m/z (%) 252 (M+, 100), 223 (23.5), 194 (18.9), 165 (22.5), 139
(19.0), 114 (19.2), 105 (18.6), 55 (15.8). Anal. Calcd for C17H16O2:
C, 80.93; H, 6.39. Found: C, 80.78; H, 6.49. E-isomer: 1H NMR
(CDCl3, 300 MHz) δ 7.40 (2H, m), 7.28 (3H, m), 6.76 (1H, d, J ) 5.7
Hz), 6.23 (1H, dd, J ) 1.8, 5.7 Hz), 5.18 (1H, d, J ) 1.8 Hz), 4.02
(1H, m), 3.85 (1H, m), 1.60-1.82 (6H, m); IR Vmax 3082, 3052, 2948,
2881, 2852, 2196, 1772, 1635, 1596, 1581, 1490, 1469, 1442 cm-1
;
EIMS, m/z (%) 252 (M+, 100), 223 (40.8), 194 (53.7), 165 (43.4), 139
(38.5), 115 (30.3), 105 (44.8), 55 (20.8). HREIMS for C17H16O2: calcd
252.1150, found 252.1171.
2-(3-Phenylprop-2-ynylidene)-1,6,9-trioxaspiro[4.5]dec-3-ene (6f:
yield, 63%) was obtained according to the procedure for 6a. Z-isomer
1
(colorless crystal): mp 100-101 °C; H NMR (CDCl3, 300 MHz) δ
7.48 (2H, m), 7.30 (3H, m), 6.41 (1H, d, J ) 6.0 Hz), 6.14 (1H, d, J
) 5.7 Hz), 4.92 (1H, s), 4.39 (1H, m), 3.87 (1H, m), 3.77 (4H, m); IR
Vmax 3102, 3050, 2964, 2914, 2863, 2195, 1636, 1594, 1583, 1488,
1451, 1440 cm-1; EIMS, m/z (%) 254 (M+, 42.3), 225 (8.3), 197 (100),
181 (12.4), 168 (25.5), 139 (44.4), 115 (31.4), 105 (17.1), 88 (11.7),
63 (12.4), 55 (11.9). Anal. Calcd for C16H14O3: C, 75.57; H, 5.55.
Found: C, 75.66; H, 5.59. E-isomer (yellow oil): 1H NMR (CDCl3,
300 MHz) δ 7.42 (2H, m), 7.32 (3H, m), 6.90 (1H, d, J ) 5.7 Hz),
6.18 (1H, dd, J ) 1.3, 5.5 Hz), 5.34 (1H, d, J ) 0.9 Hz), 4.31 (1H, m),

6722 J. Agric. Food Chem., Vol. 52, No. 22, 2004
Chen et al.
Scheme 1. Synthesis of Tonghaosu (1) and Its Analogues (6b
6l)a
3.86 (1H, m), 3.78 (4H, m); IR Vmax 3096, 3053, 2972, 2935, 2881,
2855, 2196, 1635, 1596, 1579, 1490, 1452, 1443 cm-1; EIMS, m/z
(%) 254 (M+, 46.4), 225 (5.4), 197 (100), 181 (8.4), 165 (17.4), 139
(35.0), 115 (20.3), 105 (12.1), 82 (10.2), 43 (19.3). HREIMS for
C16H14O3: calcd 254.0943, found 254.0935.
−
2-Hexa-2,4-diynylidene-1,6,9-trioxaspiro[4.5]dec-3-ene (6i) was ob-
tained as a yellow oil (yield, 45%). Z-isomer: 1H NMR (CDCl3, 300
MHz) δ 6.36 (1H, d, J ) 5.7 Hz), 6.14 (1H, d, J ) 5.7 Hz), 4.71 (1H,
s), 4.38 (1H, m), 3.87 (1H, m), 3.75 (4H, m), 2.01 (3H, d, J ) 1.2
Hz); IR Vmax 3096, 3049, 2972, 2912, 2882, 2855, 2230, 2139, 1635,
1584, 1453, 1437, 1267, 1238, 1213, 1164 cm-1; EIMS, m/z (%) 216
(M+, 94.2), 187 (9.4), 171 (8.6), 159 (100), 131 (38.8), 115 (55.2),
102 (62.0), 83 (57.5), 77 (64.2), 50 (70.5). HREIMS for C13H12O3:
calcd 216.0781, found 216.0784. E-isomer: 1H NMR (CDCl3, 300
MHz) δ 6.79 (1H, d, J ) 6.0 Hz), 6.22 (1H, dd, J ) 1.8, 6.0 Hz), 5.11
(1H, s), 4.26 (1H, m), 3.84 (1H, m), 3.75 (4H, m), 1.99 (3H, d, J )
1.5 Hz); IR Vmax 3095, 3046, 2972, 2937, 2912, 2883, 2855, 2231, 2141,
1629, 1579, 1452, 1438, 1283, 1265, 1238, 1199 cm-1; EIMS, m/z
(%) 216 (M+, 100), 187 (9.4), 171 (8.4), 159 (96.3), 131 (34.6), 115
(47.6), 102 (50.3), 82 (28.2), 77 (56.3), 50 (54.4). HREIMS for
C13H12O3: calcd 216.0781, found 216.0792.
5-[3-(1,6-Dioxaspiro[4.4]non-3-en-2-ylidene)prop-1-ynyl]benzo[1,3]-
dioxole (6j) was obtained as a pale yellow solid (yield, 92%).
Z-isomer: mp 60-61 °C; H NMR (CDCl3, 300 MHz) δ 6.99 (1H,
1
a Reagents and conditions: (a) n-BuLi, TMEDA/THF,
MeOH/H2O; (c) CuSO4 5H2O, toluene, 90 110 C.
−78 °C; (b) K2CO3,
‚
−
°
dd, J ) 1.7, 8.3 Hz), 6.92 (1H, d, J ) 1.5 Hz), 6.74 (1H, d, J ) 8.1
Hz), 6.29 (1H, d, J ) 5.4 Hz), 6.13 (1H, dd, J ) 0.8, 5.6 Hz), 5.97
(2H, s), 4.79 (1H, s), 4.27 (1H, m), 4.01 (1H, m), 2.31 (2H, m), 2.08
(2H, m); IR Vmax 3095, 3047, 2986, 2958, 2895, 1712, 1641, 1602,
1586, 1503, 1488, 1443, 1348 cm-1; HREIMS for C17H14O4: calcd
282.0829, found 282.0908. E-isomer: mp 92-93 °C; 1H NMR (CDCl3,
300 MHz) δ 6.93 (1H, dd, J ) 1.6, 7.9 Hz), 6.87 (1H, d, J ) 1.2 Hz),
6.76 (2H, t, J ) 6.9 Hz), 6.22 (1H, dd, J ) 1.6, 5.8 Hz), 5.97 (2H, s),
5.13 (1H, d, J ) 1.5 Hz), 4.21 (1H, m), 4.01 (1H, m), 2.02-2.34 (4H,
m); IR Vmax 3088, 2981, 2893, 1639, 1598, 1584, 1504, 1490, 1474,
1444, 1222 cm-1; EIMS, m/z (%) 282 (M+, 100), 251 (25.0), 225 (13.9),
197 (17.8), 149 (37.1), 126 (15.5), 74 (17.3). Anal. Calcd for
C17H14O4: C, 72.33; H, 5.00. Found: C, 72.35; H, 4.86.
Table 1. Antifeeding Activity of Tonghaosu and Its Analogues against
the Third-Instar Larvae of P. brassicae (Test Concentration 1000
)
µ
g/mL)
compd
antifeedancy (%)
compd
Z-1
E-6h
Z-6h
E-6i
Z-6i
E-6j
Z-6j
E-6k
Z-6k
E-6l
Z-6l
azadirachtin
antifeedancy (%)
E-6a
Z-6a
E-6b
Z-6b
E-6c
Z-6c
E-6d
Z-6d
E-6e
Z-6e
E-6f
Z-6f
59.60
47.59
67.00
39.39
45.23
12.79
0
9.82
10.62
0
88.42
85.30
89.93
46.64
92.26
51.50
93.39
50.10
96.15
77.49
93.72
92.86
5-[3-(1,6-Dioxaspiro[4.5]dec-3-en-2-ylidene)prop-1-ynyl]benzo[1,3]-
dioxole (6k: yield, 84%). Z-isomer (yellow oil): 1H NMR (CDCl3, 300
MHz) δ 6.99 (1H, dd, J ) 1.8, 8.1 Hz), 6.92 (1H, d, J ) 1.5 Hz), 6.76
(1H, d, J ) 8.1 Hz), 6.27 (1H, d, J ) 6.0 Hz), 6.17 (1H, d, J ) 6.3
Hz), 5.98 (2H, s), 4.80 (1H, s), 4.15 (1H, m), 3.87 (1H, m), 1.64-1.85
(6H, m); EIMS, m/z (%) 296 (M+, 43.5), 268 (16.8), 238 (26.2), 149
(26.3), 126 (13.1), 74 (16.7), 55 (16.1); IR Vmax 3058, 3022, 2967, 2943,
2885, 1642, 1601, 1586, 1503, 1484, 1438 cm-1. Anal. Calcd for
C18H16O4: C, 72.96; H, 5.44. Found: C, 73.07; H, 5.72. E-isomer (pale
0
0
E-1
28.22
RESULTS AND DISCUSSION
1
Scheme 1 outlines the general procedure used to synthesize
tonghaosu and its analogues. 1-Hexyne (2a) and phenylacetylene
(2b) are commercially available, whereas 2c and 2d were
prepared from corresponding aldehydes (but-2-ynal and piper-
onal) according to the general method of Corey and Fuchs (25).
Tonghaosu and its analogues 6 were prepared in good overall
yield via a three-step procedure developed by us. Thus,
acetylenic lithium salt derived from compound 2 reacted with
known furan-2-yl aldehyde 3 (6, 7, 10) to give alcohol 4, which
was subjected to potassium carbonate to afford precursor diol
5. On treatment with CuSO4‚5H2O in toluene at 90-110 °C,
diol 5 was smoothly converted to spiroketal enol ether 6 as a
mixture of Z- and E-isomers, favoring the Z-isomer. The two
isomers could be separated by flash chromatography on silica
gel with petroleum ether/ethyl acetate/triethylamine (20:1:0.005
v/v/v) as the eluent.
With the above prepared tonghaosu and its 22 analogues in
hand, we next examined their antifeeding activities by using
the conventional no-choice leaf-disk method (22). The results
are summarized in Tables 1 and 2; azadirachtin was used in
the control experiment. As can be seen from Table 1,
compounds with the 1,3-diyn function group (1, 6h, Z-6i)
demonstrated considerable antifeeding activities, whereas com-
yellow solid): mp 63-94 °C; H NMR (CDCl3, 300 MHz) δ 6.90
(1H, dd, J ) 1.5, 8.1 Hz), 6.83 (1H, d, J ) 1.5 Hz), 6.72 (1H, d, J )
8.4 Hz), 6.70 (1H, dd, J ) 0.8, 5.9 Hz), 6.19 (1H, dd, J ) 2.0, 5.9
Hz), 5.94 (2H, s), 5.12 (1H, d, J ) 1.8 Hz), 3.99 (1H, td, J ) 3.0, 11.4
Hz), 3.86 (1H, m), 1.56-1.79 (6H, m); IR Vmax 2948, 2886, 1710, 1637,
1603, 1575, 1501, 1488, 1473, 1447, 1221 cm-1. Anal. Calcd for
C18H16O4: C, 72.96; H, 5.44. Found: C, 73.15; H, 5.57.
2-(3-Benzo[1,3]dioxol-5-ylprop-2-ynylidene)-1,6,9-trioxaspiro[4.5]-
dec-3-ene (6l) was obtained as a yellow syrup (yield, 69%). Z-isomer:
1H NMR (CDCl3, 300 MHz) δ 7.01 (1H, dd, J ) 1.5, 8.1 Hz), 6.93
(1H, d, J ) 1.5 Hz), 6.75 (1H, d, J ) 8.1 Hz), 6.40 (1H, d, J ) 5.4
Hz), 6.12 (1H, dd, J ) 0.4, 5.8 Hz), 5.97 (2H, s), 4.88 (1H, s), 4.39
(1H, m), 3.72-3.91 (5H, m); IR Vmax 3096, 2975, 2903, 2856, 1735,
1643, 1504, 1488, 1444, 1249, 1224, 1211 cm-1; EIMS, m/z (%) 298
(M+, 100), 269 (6.3), 241 (88.5), 185 (11.7), 139 (17.1), 74 (12.7).
Anal. Calcd for C17H14O5: C, 68.45; H, 4.73. Found: C, 68.79; H,
5.07. HREIMS for C17H14O5: calcd 298.0841, found 298.0821.
E-isomer: 1H NMR (CDCl3, 300 MHz) δ 7.01 (1H, dd, J ) 1.5, 8.1
Hz), 6.93 (1H, d, J ) 1.5 Hz), 6.75 (1H, d, J ) 8.1 Hz), 6.39 (1H, d,
J ) 5.4 Hz), 6.12 (1H, dd, J ) 0.4, 5.8 Hz), 5.97 (2H, s), 4.88 (1H, s),
4.38 (1H, m), 3.72-3.87 (6H, m); IR Vmax 3096, 3047, 2972, 2933,
2887, 2856, 1712, 1636, 1602, 1579, 1503, 1488, 1444 cm-1. HREIMS
for C17H14O5: calcd 298.0841, found 298.0821.
For the syntheses of 5d, 5g, 5h, 6d, 1, and 6h and their physical
data see previous papers (6, 10).

Antifeeding Activities of Tonghaosu Analogues
J. Agric. Food Chem., Vol. 52, No. 22, 2004 6723
(8) Fan, J.-F.; Yin, B.-L.; Zhang, Y.-F.; Wu, Y.-L.; Wu, Y.
Molecular diversity of tonghaosu analogs. Synthesis of 2-(Z)-
benzylidene-1,6,9-trioxaspiro[4,5]dec-3-ene. Acta Chim. Sinica
2001, 59, 1756-1762 (in Chinese).
(9) Yin, B.-L.; Yang, Z.-M.; Hu, T.-S.; Wu, Y.-L. Molecular
diversity of tonghaosu: Synthesis of lactam-containing tonghaosu
analogs. Synthesis 2003, 1995-2000.
(10) Chen, L.; Yin, B.-L.; Xu, H.-H.; Chiu, M.-H.; Wu, Y.-L. Study
on tonghaosu and its analogs. Isolation, structure identification
and synthesis of antifeedant B-ring-homo-tonghaosu. Chin. J.
Chem. 2004, 22, 92-99.
(11) Zhang, Z.-X.; Xu, H.-H.; Cheng, D.-M.; Wu, Y.-L.; Fan, J.-F.
Screening derivatives of spiro enol ether and testing its toxicity
on Spodoptera litura cell with MTT method. J. South China
Agric. UniV. 2000, 21 (3), 29-32 (in Chinese).
Table 2. Antifeedant Activity (AFC50) of Active Compounds against the
Third-Instar Larvae of P. brassicae
a
compd
Z-1
Z-6h
Z-6i
Z-6j
Z-6k
Z-6l
azadirachtin
slope (
±
SE)
AFC50
(µ
g/mL)
95% CL
2.2255 (
±
±
±
±
±
±
±
0.05443)
0.08987)
0.08854)
0.1839)
0.1861)
0.1272)
0.05908)
654.78 a
204.77 a
376.47 a
323.79 a
186.61 a
413.46 a
7.15 b
226.12
−
−
−
−
−
−
−
556.63
1.8601 (
1.9517 (
2.2026 (
2.0004 (
1.9622 (
0.7008 (
126.77
224.59
207.44
116.77
242.03
1.35
330.79
631.06
505.38
298.23
706.31
37.77
a Values within a column followed by the same letter were not significantly
different.
pounds 6a-f, which contain only one triple bond, have very
low or no activity at all. However, in contrast to the lack of
activity of compounds 6d-f, Z-isomers of 6j-l, which have a
3,4-methylenedioxy substituent on the benzene ring, showed
good antifeeding activities comparable to those of compounds
1, 6h, and Z-6i. More interestingly, the Z-isomers of 6i-k
showed much higher activities than their corresponding E-
isomers, which deserves further investigation. In addition, the
modification of the B ring of tonghaosu had little effect on the
activity. All of these results suggest that besides the important
spiroketal enol ether system, the side chain of tonghaosu
analogues may also play a role in their biological activities.
However, the results listed in Table 2 indicate there were no
significant differences among these prepared active compounds,
which were all less effective than azadirachtin.
(12) Xu, H.-H.; Zhang, Z.-X.; Cheng, D.-M.; Wu, Y.-L.; Fan, J.-F.
Studies on bioactivities of derivatives of spiro enol ether against
Spodoptera litura Fabricius. J. Huazhong Agric. UniV. 2000, 19,
543-546 (in Chinese).
(13) Zhang, Z.-X.; Xu, H.-H.; Cheng, D.-M.; Wu, Y.-L.; Fan, J.-F.
Bioactivity of two spiro enol ether analogues against Pieris
rapae. J. Southwest Agric. UniV. 2001, 23, 19-21 (in Chinese).
(14) Zhang, Z.-X.; Xu, H.-H.; Cheng, D.-M.; Wu, Y.-L.; Fan, J.-F.
Studies on bioactivities of spiro enol ether analogues. J. Northeast
Agric. UniV. 2001, 32, 105-110 (in Chinese).
(15) Cheng, D.-M.; Zhang, Z.-X.; Xu, H.-H.; Wu, Y.-L.; Fan, J.-F.
Antifeedant activity of spiro enol ether analogues against
vegetable insects. J. Huazhong Agric. UniV. 2002, 21, 343-
346 (in Chinese).
(16) Yano, K. Insect antifeeding phenylacetylenes from growing buds
of Artemisia capillaris. J. Agric. Food Chem. 1983, 31, 667-
668.
(17) Yano, K. Minor components from growing buds of Artemisia
capillaris that act as insect antifeedants. J. Agric. Food Chem.
1987, 35, 889-891.
(18) Yano, K. Relationships between chemical structure of phenyl-
alkynes and their antifeeding activity for larvae of a cabbage
butterfly. Insect Biochem. 1986, 16, 717-719.
(19) Xu, H.-H.; Chiu S.-F. Studies on insecticidal activities of the
essential oil from Artemisia scoparia. J. South China Agric. UniV.
1993, 14, 97-102 (in Chinese).
In conclusion, >20 tonghaosu analogues were prepared and
characterized. Their antifeeding activity was investigated, and
compounds containing a diyn or 3,4-methylenedioxyphenyl
acetylene function group demonstrated appreciable antifeeding
activities against the third-instar larvae of P. brassicae. A further
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Received for review March 30, 2004. Revised manuscript received June
11, 2004. Accepted August 28, 2004. This project was supported by
the National Natural Science Foundation of China (Grants 29672083
and 20072043), the Chinese Academy of Sciences, the State Ministry
of Science and Technology (Grant 2000077502), and the Shanghai
Committee of Science and Technology.
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