Periplanone-B analogues as well as cockroach attractant

Periplanone-B analogue of (4E, 8R, 9R, 10R)-8,9-epoxy-5-methyl-10,10-methylene-oxy-4-cyclodecen-1-one, suitable as cockroach attractant can be prepared by reacting 6-methyl-2,6-cyclodecadien-1-one with a silylating reagent under the presence of a basic catalyst to form a silyldienol ether, reacting the resultant ether with an organic peracid to obtain (2Z, 6E)-10-hydroxy-6-methyl-2,6-cyclodecadien-1-one, reacting the resultant product with a peroxide under the presence of a basic catalyst after protecting hydroxy groups thereof with protection groups to obtain an epoxide, reacting the epoxide with chloromethyl lithium or dimethyl sulfonium methylide thereby introducing a spiroepoxy group and then removing the protection groups, to obtain (1S, 4E, 8R, 9R, 10S)-8,9-epoxy-5-methyl-10,10-methyleneoxy-4-cyclodecen-1-ol and, further, oxidizing the resultant product with a chromic acid type or dimethyl sulfoxide type oxidizing agents.

BACKGROUND OF THE INVENTION 
1. Field of the Invention 
The present invention concerns a novel periplanone-B analogue used as 
biologically active material, in particular, as attractant for 
cockroaches, etc. 
2. Description of the Prior Art 
Cockroaches are typical insanitary and unpleasant pests which invade in 
various industrial places as well as domestic houses to give great 
damages. In view of the above, although various controlling methods have 
been used, use of insecticides suffer from restrictions since their 
habitats are closely related with human livings. In addition, effective 
control can not be obtained by conventional insect trapping means since 
cockroaches have a habit of hiding themselves in narrow gaps, etc. and 
have a strong reproducibility and they would be repeat infestation even 
after control. 
In recent years, studies have been developed for pheromones of cockroaches 
and the study for using them to the control of cockroaches has been 
started. Pheromones are chemical substances secreted from insects for the 
preservation of species and it has been known that pheromones show potent 
activity such as attraction even in a very minute amount. Accordingly, it 
is considered that a pheromone can provide effective and non-toxic novel 
control means if it is used as an attractant for insect catching means. 
By the way, periplanone-B is a compound having the structure represented by 
the following formula (B): 
##STR1## 
which is a major component of a sex pheromone secreted from female 
American cockroach (Periplaneta americana), which attracts male 
cockroaches to cause sexual excitation even in a amount of 10.sup.-6 
-10.sup.-7 .mu.g. The compound (B) was isolated and determined for the 
structure by Persoons, et al. (C. J. Persoons, et al., Tetrahedron 
Letters, 24, 2055 (1976)) and its stereochemistry was determined by Still, 
Nakanishi, et al (W. C. Still, J. Am. Chem. Soc., 101, 2493 (1979); K. 
Nakanishi, et al., J. Am. Chem. So., 101, 2495 (1979)). 
The synthesizing process has been reported, in addition to the Still's 
method as described above, also by Schreiber, et al (S. L. Schreiber, et 
al., J. Am. Chem. Soc., 106, 4038 (1984)), Hauptmann, et al. (Hauptmann, 
et al., 27, 1315 (1986)), Kitahara, et al. (T. Kitahara, et al., 
Tetrahedron Lett., 27, 1343 (1986)), Takahashi, et al (T. Takahashi, et 
al., J. Org. Chem., 51, 3394 (1986)), De Clercq, et al., (P. J. De Clercq, 
et al., Tetrahedron Lett., 29, 6501 (1988)). 
In addition, a minor pheromone component, periplanone-A is also known (C. 
J. Persoons, et al., J. Chem. Ecol., 5, 22 (1979); H. Hauptmann, et al., 
Tetrahedron Lett., 27, 6189 (1986)), and the structure has recently been 
determined (M. Mori, et al., J. Chem. Soc. Perkin Trans, 1, 1769 (1990)). 
Other kinds of substances having sexual pheromone activity much weaker than 
that of natural pheromones, which are known as mimics, have also been 
found and there are known bornyl acetate (W. S. Bowers, et al., Nature, 
232, 259 (1971)), germacrene-D (S. Takahashi, et al., Agric. Biol. Chem., 
39, 1517 (1975)), verbenyl ester, verbanyl ester (C. Nishino, et al., 
Appl. Entomol. Zool., 12, 287 (1977)). 
For applying the known pheromones and mimics as described above to the 
control of American cockroach (Periplaneta americana) there are the 
following problems. 
Periplanone-B can be obtained only by 0.2 mg even when collected from 
75,000 cockroaches and it is impossible to use extractants from insects as 
an attractant. Accordingly, it is necessary for the mass production by an 
organic synthesis process. 
However, there are the following difficulties: 
(1) Synthesis for 10-membered carbon rings as the fundamental skelton is 
difficult, for which no practical production process has yet been 
established, 
(2) Since the compound has many asymmetric carbon atoms and its 
stereoisomers show no activity, it requires a highly skillfull 
stereo-controlling method in view of synthesis. 
(3) Since the compound has an unstable structure such as epoxy group or 
diene in the molecule, it is easily decomposed, 
(4) Since existent synthetic processes require lengthy production steps 
because many functional groups have to be introduced in a stereoselective 
manner and many reactions such as organic metal reactions or cyclizing 
reactions requiring accurate condition settings are used, they are not 
practical. 
In addition, since known pheromonally active substances (mimics), even 
powerful ones, have activity only to 1/1,000,000 of natural products, they 
have even not yet been put to practical use at present. 
SUMMARY OF THE INVENTION 
In view of the foregoing problems, the present inventors have made an 
earnest study with an aim of developing a practically useful pheromone 
derivative. As a result, we have obtained a knowledge based on the 
detailed analysis for the conformation of known active substances and the 
study on the structure-activity relationships that the conformation and 
steric coordination of oxygen-containing functional groups in the 
10-membered ring are important for the development of the activity. Then, 
we have designed the present compound (A) having a structure in which 
isopropyl group and exomethylene group other than the functional carbon 
groups are removed from periplanone-B, that is, (4E, 8R, 9R, 
10R)-8,9-epoxy-5-methyl-10,10-methyleneoxy-4-cyclodecen-1-one. 
##STR2## 
The compound (A) according to the present invention can be prepared by 
reacting 6-methyl-2,6-cyclodecadien-1-one with a silylating agent under 
the presence of a basic catalyst to form a silyldienol ether, reacting the 
resultant ether with an organic peracid to form (2Z, 
6E)-10-hydroxy-6-methyl-2,6-cyclodecadien-1-one, reacting it with a 
peroxide under the presence of a basic catalyst after protecting hydroxy 
groups thereof with protective groups to form an epoxide, reacting the 
epoxide with chloromethyl lithium or dimethyl sulfonium methylide, to 
thereby introducing a spiroepoxy groups, removing the protective groups to 
obtain (1S, 4E, 8R, 9R, 
10S)-8,9-epoxy-5-methyl-10,10-methyleneoxy-4-cyclodecen-1-ol and, further, 
oxidizing the resultant product with a chromic acid type oxidizing agent 
or dimethylsufoxide type oxidizing agent. 
The thus obtained compound (A) according to the present invention is a 
crystalline compound and has a steric arrangement and conformation 
identical with those of periplanone-B (B). Referring to the biological 
activity, it has an intense attracting and sexual exciting activity at an 
activity threshold value of 10.sup.-3 .mu.g to male American cockroach 
(Periplaneta americana). 
The starting material for preparing the compound (A) according to the 
present invention, that is, 6-methyl-2,6-cyclodecadien-1-one (compound 
(C)) is a known material easily obtained by a fragmentation reaction which 
is a method capable of forming a 10-membered ring which conveniently and 
in a large scale. For instance, it can be prepared by the method of 
Warton, et al. (J. Org. Chem., 36, 2932 (1971)). 
The physicochemical properties of the compound (C) are as shown below. 
Boiling point: 82.degree.-82.5.degree. C. (1.5 mmHg) 
Refractive Index (n.sub.D.sup.24.5): 1.5148 
IR (cm.sup.-1): 3016(w), 2932(s), 2860(s), 1684(s), 1620(s), 1454(s), 
1404(s), 1249(m), 1224(m), 1199(m), 1181(s), 1093(s), 942(s), 830(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 1.46(3H, J=1.4 Hz), 
1.89(2H, br), 1.95(2H, m), 2.11(2H, m, H-8), 2.26(2H, br.), 2.43(2H, br.), 
4.78(1H, br. t, J=6.5, H-7), 5.71(1H, dt, J=11.6, 8.6 Hz, H-2), 6.29(1H, 
d, J=11.6 Hz, H-1) 
Molecular formula: C.sub.11 H.sub.16 O 
Molecular weight: 164 
The compound (A) according to the present invention can be synthesized 
starting from the compound (C) and by way of each of the following steps. 
First step: 
The compound (C) is at first treated with 1 to 5 molar equivalents, 
preferably, 1.1 to 1.5 molar equivalents of a strong base, for example, 
n-butyl lithium, lithium diisopropylamide and sodium hydride, preferably, 
lithium diisopropylamide in an inert gas stream such as anhydrous nitrogen 
or argon, in a solvent, for example, an ether type solvent such as diethyl 
ether or tetrahydrofuran, or hydrocarbon solvent such as hexane or toluene 
either alone or as a mixture, preferably, tetrahydrofuran, for 0.5 to 3 
hours, preferably, one hour at a temperature lower than 0.degree. C., 
preferably, from -20.degree. to -40.degree. C. to enolization. 
Then, when 1 to 5 equi-molar amount, preferably, 1.1 to 2 molar equivalents 
of a silylating reagent, for example, trimethylsilyl chloride, 
triethylsilyl chloride or t-butyl-dimethylsilyl chloride, preferably, 
trimethylsilyl chloride is added and reacted for 0.5 to 2 hours and the 
reaction product is concentrated as it is under a reduced pressure, coarse 
silyl dienol ether is obtained. The coarse product is reacted with from 1 
to 2 molar equivalents of an organic peracid, preferably, 
m-chloroperbenzoic acid using a hydrocarbon solvent, for example, n-hexane 
or chloroform, preferably, n-hexane for 0.5 to 2 hours at a temperature 
lower than 0.degree. C., preferably, from -10.degree. to -20.degree. C. 
till the starting material is completely consumed, to obtain a 
hydroxyketone compound (D). 
Second step: 
Hydroxy group in the compound (D) obtained by the first step are brought 
into reaction with silyl type protecting reagent such as trimethylsilyl 
chloride, triethylsilyl chloride or t-butyldimethylsilyl chloride, acetal 
type protecting reagent such as ethyl vinyl ether, dihydropyrane or 
2,2-dimethoxypropane, or ether type protecting reagent such as alkyl 
halide, to obtain a protected compound (E). 
In this case, when triethylsilyl chloride is used, for example, as the 
protecting reagent, from 1 to 2 molar equivalents of the reagent is 
preferably reacted at a room temperature from 2 hours to one night by 
using pyridine as the solvent. In a case of using t-butyldimethylsilyl 
chloride, 1 to 3 molar equivalents of the reagent is preferably reacted at 
a room temperature or at 30.degree.-60.degree. C. from 2 hours to one 
night by using dimethylformamide as the solvent and imidazole as the 
catalyst. Further, in a case of using ethyl vinyl ether as the protecting 
reagent, a method of reacting 1.5 to 3 molar equivalents of the reagent at 
a room temperature from 2 hours to one night by using methylene chloride 
as the solvent can be utilized. 
Third step: 
The protected compound (E) obtained by the second step is added in an inert 
gas stream while using an ether type solvent such as diethyl ether or 
tetrahydrofuran into a mixture of 1 to 4 molar equivalents, preferably, 
1.5 molar equivalents of an organic peroxide, for example, t-butyl 
peroxide and 1 to 4 molar equivalents, preferably, 1.4 equi-molar amount 
of a strong base, for example, sodium hydride, potassium hydride and 
Triton-B, preferably, potassium hydride at a temperature lower than 
10.degree. C., preferably, from -10.degree. to -20.degree. C., and reacted 
as they are for 0.5 to 4 hours, to obtain an epoxy ketone (compound (F)). 
Fourth step: 
The compound (F) obtained by the third step is brought into reaction with a 
mixture of 1 to 4 molar equivalents, preferably, 1.5 molar equivalents of 
chlromethyl iodoxide or trimethyl sulfonium iodide and from 1 to 4 molar 
equivalents of a strong base, preferably, n-butyl lithium, methyl lithium, 
lithium diisopropylamide or sodium hydride, in an inert gas stream while 
using, for example, an ether type solvent such as diethyl ether or 
tetrahydrofuran alone or as a mixture thereof with dimethylsulfoxide, at a 
temperature, for example, from -40.degree. to 10.degree. C. and from 0.5 
to 2 hours, thereby introducing spiroepoxy groups to obtain a bisepoxide 
(compound (G)). 
Fifth step: 
Since hydroxy groups are protected in the compound (G) obtained by the 
fourth step, the thus protected hydroxy groups are deprotected by using an 
appropriate deprotecting agent, for example, tetra-n-butylammonium 
fluoride, hydrogen fluoride or potassium fluoride if the protective group 
is the silyl type protective group, hydrogen chloride, sulfuric acid, 
p-toluene sulfonic acid, pyridinium-p-toluene sulfonate or acetic acid if 
the protection group is the acetal type protective group, or hydrogen 
halide or other acid catalyst if the protection group is the ether type 
protection group respectively, to obtain a hydroxy bisepoxide (compound 
(H)). 
Sixth Step: 
The compound (H) obtained by the fifth step is oxidized by using 1 to 10 
molar equivalents, preferably, 2 molar equivalents, based on the 
substrate, of a chromic acid type oxidizing agent, for example, pyridinium 
chlorochromate, pyridinium chlorochromate-molecular sieves 3A, pyridinium 
dichromate or other oxidizing agents such as dimethylsulfoxideoxalyl 
chloride or dimethylsulfide-N-chlorosuccinimide, preferably, pyridinium 
chlorochromate-molecular sieves 3A in a solvent, for example, methylene 
chloride or chloroform, preferably, methylene chloride at a temperature 
lower than the room temperature, preferably, at 0.degree. C. for 1 to 3 
hours, to obtain a compound (A) according to the present invention.

EXAMPLE 
The present invention will now be explained more specifically referring to 
examples. 
First Step: 
A solution of lithium diisopropylamide was prepared from 2.6 ml of 
diisopropylamine and 2.8 ml of 1.6M n-butyl lithium in an argon gas stream 
at -10.degree. C. using anhydrous tetrahydrofuran as a solvent, to which 
2.0 g of the compound (C), i.e., 6-methyl-2,6-cyclodecadien-1-one was 
added dropwise under stirring at -20.degree. C. for 3 min. After stirring 
the mixture for 15 min, 2.4 ml of trimethyl silyl chloride was added 
altogether and the temperature was elevated to a room temperature under 
stirring. The reaction mixture was directly concentrated under a reduced 
pressure to obtain coarse silyldienol ether. 2.6 g of m-chloroperbenzoic 
acid was suspended in 100 ml of hexane and stirred at -15.degree. C. for 
30 min, to which the above-mentioned coarse product was added and stirred 
vigorously at -15.degree. to -20.degree. C. for 1.5 hr. After the reaction 
was completed, the reaction mixture was filtered under suction, and 
precipitates were washed with hexane and the liquid filtrate and the 
washing solution were combined and concentrated under a reduced pressure. 
The resultant oily product was purified on a column chromatography using 
50 g of silica gel to obtain 1.4 g (64% yield) of (2Z, 
6E)-10-hydroxy-6-methyl-2,6-cyclodecadien-1-one (compound (D)). 
The physicochemical properties of the compound are as shown below. 
Nature: waxy 
Refractive index (n.sub.D.sup.24.5)m: 1.5267 
IR (cm.sup.-1): 3454(br, s), 3016(w), 2924(s), 2860(s), 1680(s), 1620(s), 
1454(s), 1390(s), 1257(s), 1191(s), 1071(s), 772(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 1.37(3H, s, CH.sub.3), 
1.50(1H, m, H-5), 2.05(1H, m, H-9), 2.1-2.3(2H, m, H-4,5), 2.35(1H, m, 
J-9), 2.79(1H, m, H-3), 2.35(1H, m, H-9), 3.98(1H, br. s., OH), 4.16(1H, 
br. dt, J=4.3, 2.5 Hz, H-10), 4.63(1H, br. d, J=11.8 Hz, H-7), 5.87(1H, 
ddd, J=11.6, 9.7, 7.4 Hz, H-3), 6.30(1H, dd, J=11.6, 1.1 Hz, H-2) 
Molecular formula: C.sub.11 H.sub.16 O.sub.2 
Second Step: 
The compound (D) obtained by the first step was dissolved by 604 mg into 6 
ml of anhydrous pyridine, to which 0.85 ml of triethylsilyl chloride was 
added dropwise and reacted at room temperature for 2 hr. After the 
reaction was completed, pyridine was removed by concentration under a 
reduced pressure and the residue was extracted twice with n-hexane with 
addition of water. After washing the organic phase with water and a 
saturated solution of aqueous sodium chloride, it was dried with anhydrous 
magnesium sulfate and the solvent was removed. The resultant coarse 
product was subjected to column chromatography using 20 g of silica gel, 
to obtain 725 mg (72% yield) of (2Z, 
6E)-10-triethylsilyloxy-6-methyl-2,6-cyclodecadien-1-one (compound (E)). 
The physicochemical properties of the compound are as shown below. 
Nature: waxy 
Refractive index (n.sub.D.sup.24.5): 1.4937 
IR (cm.sup.-1): 3020(w), 2920(s), 2880(s), 1688(s), 1620(s), 1458(s), 
1093(s), 1015(s), 837(s), 729(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 0.63(6H, q, J=8.0 Hz, 
Si(C.sub.2 H.sub.5).sub.3), 0.97(9H, t, J=8.0 Hz, Si(C.sub.2 
H.sub.5).sub.3), 1.44(3H, s, CH.sub.3), 1.7-2.8(8H, br), 4.07(1H, br. s, 
H-10), 4.9(1H, br., H-7), 5.8(1H, br. m, H-3), 6.6(1H, br., H-2) 
Molecular formula: C.sub.17 H.sub.30 O.sub.2 Si 
Third Step: 
In an argon gas stream, 75 mg of potassium hydride removed with mineral 
oils was suspended in 10 ml of anhydrous tetrahydrofuran and under 
stirring at -15.degree. C., 0.8 ml of toluene solution containing 
t-butylhydroperoxide was added and stirred for 30 min, to which 1 ml 
solution of tetrahydrofuran containing 500 mg of the compound (E) obtained 
in the second step described above was added dropwise and reacted at 
-15.degree. to -20.degree. C. for 2 hr. After the reaction was completed, 
water and a saturated solution of aqueous ammonium chloride were added and 
extracted for three times with methylene chloride. The aqueous phase was 
washed with a saturated solution of aqueous sodium chloride and then dried 
over magnesium sulfate, and the solvent was removed after filtration to 
obtain a coarse product. The product was subjected to column 
chromatography using 15 g of neutral aluminum (activity II), to obtain 295 
mg (56% yield) of (2S, 5E, 9R, 10R)-9,10-epoxy- 
6-methyl-2-triethysilyloxy-5-cyclodecen-1-one (compound (F)). 
The physicochemical properties of the compound are as shown below. 
Nature: waxy 
Refractive index (n.sub.D.sup.24.5): 1.4913 
IR (cm.sup.-1): 2958(s), 2880(s), 1717(s), 1458(s), 1419(s), 12 43(m), 
1114(s), 1017(s), 845(s), 745(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 0.69(6H, q, J=8.0 Hz, 
Si(C.sub.2 H.sub.5).sub.3), 1.01(9H, t, J=8.0, Si(C.sub.2 H.sub.5).sub.3), 
1.43(1H, m, H-3), 1.58(3H, s, CH.sub.3), 1.81(1H, m, H-4), 1.9-2.0(2H, m, 
H-7,8), 2.1-2.2(2H, m, H-3',4'), -2.3(2H, m, H-7',8'), 3.23(1H, ddd, 
J=10.3, 4.8, 3.0 Hz, H-2), 4.27(1H, br. d, J=6.2 Hz, H-6), 4.28(1H, d, 
J=4.8 Hz, H-1), 4.95(1H, br., H-6) 
Molecular formula: C.sub.17 H.sub.30 O.sub.3 Si 
Fourth Step: 
(a) In an argon gas stream, 280 mg of the compound (F) obtained by the 
third step described above and 0.1 ml of chloromethyl iodide were 
dissolved in 3 ml of anhydrous tetrahydrofuran and cooled to -78.degree. 
C. 1 ml of an ether solution containing 1.2M methyl lithium was dropped to 
the solution under stirring and the temperature was elevated to a room 
temperature after stirring for 2 min. After the reaction was completed, an 
saturated solution aqueous of ammonium chloride was added and extracted 
twice with diethyl ether. After washing the organic phase with water and a 
saturated solution of aqueous sodium chloride, it was dried with magnesium 
sulfate, filtered and then the solvent was removed. The product was 
subjected to column chromatography using 10 g of neutral silica gel to 
obtain 248 mg (85% yield) of (1S, 4E, 8R, 9R, 
10R)-8,9-epoxy-5-methyl-10,10-methyleneoxy-4-chclodecen-1-ol-triethylsilyl 
ether (compound (G)). 
The physicochemical properties of the compound are as shown below. 
Nature: waxy 
IR (cm.sup.-1): 3062(w), 2918(s), 2880(s), 1460(s), 1296(m), 1270(m), 
1241(s), 1083(s), 1006(s), 946(s), 806(s), 745(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 0.58(6H, q, J=8.1 Hz, 
Si(C.sub.2 H.sub.5).sub.3), 0.95(9H, t, J=8.1 Hz, Si(C.sub.2 
H.sub.5).sub.3), 1.70(3H, s, CH.sub.3), 1.7-2.1(8H, m), 2.35(1H, d, J=6.2 
Hz, spiroepoxy), 2.76(1H, d, J=6.2 Hz, spiroepoxy), 2.99(1H, dt, J=10.5, 
3.9 Hz, H-8), 3.25(1H, dd, J=10.8, 4.5 Hz, H-1), 3.38(1H, d, J=3.9 Hz, 
H-9), 5.17(1H, br. H-4) 
Molecular formula: C.sub.18 H.sub.32 O.sub.3 Si (b) The compound (G) was 
synthesized from the compound (F), separately from the above, as shown 
below. 
In an argon gas stream, 204 mg of trimethylsulfonium iodide was suspended 
in 3 ml of anhydrous tetrahydrofuran and cooled to -15.degree. C. Then, 
0.65 ml of a hexane solution containing 1.6M n-butyl lithium was added 
dropwise under stirring and, after stirring for 10 min, the temperature 
was elevated once to a room temperature to form a homogenous solution. The 
solution was again cooled to -10.degree. C., to which 78 mg of the 
compound (F) was added dropwise and reacted for 1 hr. 
After the reaction was completed, a saturated solution of aqueous ammonium 
chloride was added and extracted twice with diethyl ether. After washing 
the organic phase with water and a saturated solution of aqueous sodium 
chloride, it was dried with magnesium sulfate, filtered and then removed 
with the solvent. The product was subjected to silica gel column 
chromatography, to obtain 39 mg (48% yield) of a pure compound (G). 
Fifth Step: 
The compound (G) obtained by the fourth step described above was dissolved 
by 140 mg into 0.5 ml of anhydrous tetrahydrofuran, to which 0.5 ml of 
1M-tetrabutylammonium fluoride was added and stirred at 25.degree. C. for 
30 min. Diethyl ether was added and extracted three times. After washing 
the extracted organic phase with a saturated solution of sodium aqueous 
chloride, it was dried with magnesium sulfate, filtered and then removed 
with the solvent. The product was subjected to column chromatography using 
5 g of neutral silica gel, to obtain 80 mg of crystals (90% yield) of (1S, 
4E, 8R, 9R, 10S)-8.9-epoxy-5-methyl-10,10-methyleneoxy-4-cyclodecen-1-ol 
(compound (H)). 
The physicochemical properties of the compound are as shown below. 
Melting point: 83.degree.-85.degree. C. 
IR (cm.sup.-1): 3460(br. s), 3060(w), 2930(s), 2858(s), 1460(s), 1435(s), 
1272(m), 1156(m), 1048(s), 1009(s), 936(s), 897(s), 837(s), 702(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 1.71(3H, s, CH.sub.3), 
1.7-1.9(3H, m), 1.9-2.2(5H, m), 2.46(1H, d, J=6.1 Hz, spiroepoxy), 
2.79(1H, d, J=6.1 Hz, spiroepoxy), 3.03(1H, dt, J=10.6, 4.0 Hz, H-8), 
3.23(1H, dd, J=11.4, 4.5 Hz, H-1), 3.31(1H, d, J=4.0 Hz, H-9), 5.14(1H, 
br., H-6) 
Molecular formula: C.sub.12 H.sub.18 O.sub.3 
Sixth Step 
In anhydrous methylene chloride, 150 mg of pyridinium chlorochromate and 
350 mg of molecular sieve-3A were vigorously stirred, to which 76 mg of 
the compound (H) was added and oxidized at 0.degree. C. for 1 hr. Diethyl 
ether was added to the reaction mixture and insoluble matters were removed 
by filtration in a short column of florisil and the solvent was removed to 
obtain a coarse product. The coarse product was subjected to column 
chromatography using 5 g of neutral silica gel, to obtain 55 mg (73% 
yield) of pure (4E, 8R, 9R, 
10R)-8,9-epoxy-5-methyl-10,10-methyleneoxy-4-cyclodecen-1-one (compound 
(A)). 
The physicochemical properties of the compound are as shown below. 
Melting point: 66.6.degree.-68.degree. C. 
IR (cm.sup.-1): 2992(m), 2932(m), 2868(m), 1709(s), 1450(m), 1332(m), 
1267(m), 1046(m), 1017(m), 922(s), 835(s), 787(m), 704(m), 571(s) 
.sup.1 H-NMR(300 MHz, CDCl.sub.3, .delta., ppm): 1.62(3H, d, J=1.4 Hz, 
CH.sub.3), 1.78(1H, m, H-6), 1.87(1H, m, H-7), 2.01(1H, ddd, J=12.8, 5.4, 
2.7 Hz, H-2), 2.17(1H, m, H-7'), 2.23(1H, br., H-3), 2.43(1H, br., H-6'), 
2.63(1H, m, H-3'), 2.72(1H, d, J=5.7 Hz, spiroepoxy), 2.91(1H, ddd, 
J=12.5, 10.0, 3.0 Hz, H-2'), 2.97(1H, d, J=5.7 Hz, spiroepoxy), 2.98(1H, 
dt, J=10.7, 3.8 Hz, H-8), 3.82(1H, J=3.8, 0.4 Hz, H-9), 5.49(1H, m, H-4) 
Molecular formula: C.sub.12 H.sub.16 O.sub.3 
TEST EXAMPLE 
Filter paper was laid on the bottom of a glass vessel sized 12.5 cm length, 
18.5 cm width and 29 cm height with its upper surface being opened, and a 
black line was drawn along the center part of the filter paper so as to 
bisect the lateral length. Then, a wooden box sized 5.8 cm length, 7.7 cm 
height and 12.5 cm width and partitioned in the direction of the width 
into 7 compartments was attached to the glass vessel laterally in 
connection with an opening of 7.7 cm height formed to the lower portion of 
the longitudinal side of the vessel to constitute a shelter. 
A diluted solution of a test specimen in hexane was introduced together 
with an air stream at a rate of 200 ml/min from a glass nozzle attached to 
the upper portion of the test vessel. 
Five unmated 4-12 week aged male American cockroach (Periplaneta americana) 
after imaginal ecdysis were set free in a testing vessel under red light. 
When left as they were for 10 min, all of them entered into the shelter 
and stood still. In this state, the diluted solution of the test specimen 
in hexane was introduced and (1) the number of times that cockroaches 
getting out of the shelter and passed across the black line at the bottom 
of the vessel within one minute after the introduction of the test 
specimen was counted and it was defined as the attracting activity and (2) 
the number of cockroaches, among five, that showed wing-raising as the 
typical mating behavior was counted and it was defined as the sexual 
excitation activity. 
In this test, germacrene-D known as an effective pheromone mimic (control 
product (X)) and the compound (A) according to the present invention were 
introduced, as the test specimens, into the testing vessel such that their 
amounts was varied or changed by 10 times, and measurement was conducted 
by three times an each introduced amount, to determine the relationship 
between the amount of introduction and the activity. The results are as 
shown in Table 1 and it has been found that intense attracting and sexual 
excitation activity are shown at an activity threshold of 10.sup.-3 .mu.g 
against male American cockroach (Periplaneta americana). 
TABLE 1 
______________________________________ 
Amount Sexual 
introduced 
Attracting 
excitation 
No. Compound .mu.g activity activity 
______________________________________ 
1 (A) 1 68 5/5 
2 " 10.sup.-1 54 5/5 
3 " 10.sup.-2 40 5/5 
4 " 10.sup.-3 27 3/5 
5 " 10.sup.-4 2 1/5 
6 " 10.sup.-5 0 0/5 
7* (X) 10 17 3/5 
8* " 1 1 0/5 
9* " 10.sup.-1 0 0/5 
10* hexane (solvent) 0 0/5 
alone 
______________________________________ 
*: control experiment 
The threshold activity of pheromone mimic for American cockroach 
(Periplaneta americana) known at present is about 1 .mu.g even with the 
strongest one, and the compound (A) according to the present invention has 
an activity greater by more than 1000 times as compared therewith. 
Further, since the structure of the compound (A) is simple, the production 
steps can be shortened remarkably as compared with those for natural 
products. Furthermore, since the compound contains not so many unstable 
groups and asymmetric carbon atoms, the molecule is highly stable and 
there is not trouble for the steric control. In addition, since a 
convenient fragmentation reaction can be utilized for the formation of the 
10-membered ring which is a key reaction to the synthesis of the 
periplanone derivative, this is more advantageous than the prior art 
process. 
The compound (A) according to the present invention has excellent 
properties as described above and is extremely useful for the control of 
cockroaches.