Phosphorus Insecticides Against Organophosphorus- Resistant Rice Stem Borers*

Home , Isoxathion, Oxon (chemical), Pirimicarb

J. Pesticide Sci. 15, 175-187 (1990)

Original Article

Aryl N, N-Dirnethylcarbamates, Synergists for Organo- phosphorus Insecticides against Organophosphorus- resistant Rice Stem Borers*

Yasuhiko KoNNO and Takashi SHISHIDO

Division of Pesticides, National Institute of Agro-Environmental Sciences, Kannondai, Tsukuba 305, Japan

(Received September 1, 1989)

One hundred noninsecticidal carbamates were synthesized and evaluated as synergists for fenitrothion and pirimiphos-methyl against the OP-resistant rice stem borer. Substituted aryl (including phenyl and heterocyclic groups) N,N-dimethylcarbamates had a synergistic activity. In substituted phenyl esters, the order of positional effectiveness of the substituent group on the benzene ring was para meta>ortho. 3-Methyl-4-nitrophenyl (SK-2) and 3-methyl-4- methylthiophenyl (SK-9) esters were excellent synergists. In substituted heterocyclic esters, 5-phenyl-3-isoxazolyl (SK-40) and 2-dimethylamino-6-methyl-4-pyrimidinyl (SK-102) esters were extremely effective, and the latter reduced the resistance level against pirimiphos-methyl from 1202 to 1.1-fold. When the aryl esters of N,N-dimethylcarbamate were changed to corresponding N, N-diethyl-, N, N-dimethylthio-, and N, N-dimethylthiolcarbamates, their synergistic activities decreased from 1/18 to 1/2 that of N, N-dimethylcarbamates. Aryl esters of N-methyl-, N-ethyl- and N-phenylcarbamates, and aliphatic esters of N, N-dimethylcarbamates were inactive. SK-2, -9, -40 and -102 had no synergistic activity against the susceptible strain. The synergistic mechanism of SK-102 for fenitrothion was strong inhibition of fenitroxon detoxication by binding protein and hydrolysis.

a level equal to that of the susceptible strain. INTRODUCTION On the other hand, we have revealed that Several synergism studies against the or- the OP-resistant rice stem borer shows high ganophosphorus (OP)-resistant rice stem borer, levels of resistance to 0,0-dimethyl 0-aryl Chilo suppressalis WALKER,have been done phosphorothioates and phosphates such as since it appeared in Okayama prefecture in fenitrothion, pirimiphos-methyl and their 1978, and such chemicals as IBP,1,2) edifen- oxons.4,6) Our in vivo and in vitro studies phos1) and pirimicarb3) were found as syner- have shown that increased detoxication of gists. We have tested various noninsecticidal fenitroxon by cleavage of the P(O)-O-aryl OP compounds as synergists for f enitrothion, bond is the main mechanism of f enitrothion and found that K-2 and DEF have a synergistic resistance,4,7) and that both protein-binding acti.vity.4,5) Although K-2 and DEF were and hydrolysis of fenitroxon in a soluble frac- more active than IBP, edifenphos and pirimi- tion from the OP-resistant rice stem borer carb, neither of them was capable of increasing play an important role in the fenitroxon detoxi- the susceptibility of the OP-resistant strain to cation. 8) These facts suggest that oxon de- * This work was supported in part by a Grant-in- toxication sites of the binding protein and Aid (Bio Media Program) from the Ministry of hydrolysis in the OP-resistant rice stem borer Agriculture, Forestry and Fisheries (BMP 90-IV- had a high affinity for the structure of 0, 0- 2-1) dimethyl 0-aryl phosphate. 176 日本農薬学会誌第15巻第2号平成2年5月

In synergism theory, analog synergists are shimacho, Saitama prefecture in 1971 by the defined as synergists whose structure closely Institute of Physical and Chemical Research. resemble that of an insecticide they synergize. The rearing methods of the two strains were An analog synergist competes with the in- described previously.5) Fifth instar larvae secticide for the same detoxication site and (body weight: 60 to 70 mg) of the two strains exhibits synergism by occupying and blocking were used in this study. the detoxication site.9) One extensive study on the evaluation of noninsecticidal carbamates 2. Chemicals as synergists for Isolan and carbaryl has done A considerable number of N,N-dialkyl- by using houseflies.10) carbamates or -thionocarbamates were pre- We attempted to obtain analog syner- pared by reacting respective N,N-dialkyl- gists from these points of view. The N,N- carbamoyl chlorides or N,N-dimethylthio- dimethylcarbamoyloxy group was selected carbamoyl chlorides with appropriate phenols, as a fundamental skelton, because the alcohols and isoxazols in an excess of dry (CH3)2NC (O) O-moiety of carbamate ester re- pyridine (Method A).11) Heterocyclic esters sembles the (CH3O)2P(O)O-moiety of OP ester of N,N-dialkylcarbamates were prepared by in structure and function, and an N,N-di- treating N, N-dialkylcarbamoyl chlorides either methylcarbamate insecticide, pirimicarb (2-di- with heterocyclic enol in the presence of an methylamino-5, 6-dimethyl - 4 -pyrimidinyl N, acid-consuming agent, anhydrous potassium N-dimethylcarbamate), is already known to be carbonate in dry acetone solution (Method active as a synergist against the OP-resistant B)12) or directly with sodium enolate in dry rice stem borer.3) Furthermore, in order to toluene solution (Method C-1)13,14)and in dry enhance an affinity for the detoxication site, methyl ethyl keeone solution (Method C-2). the substituted phenyl group of OP esters, to Alkyl or thiophenyl esters of N, N-dimethyl- which the OP-resistant rice stem borer showed carbamates were prepared from N, N-dimethyl- the high level of resistance, was chosen as the carbamoyl chloride and sodium salts of phenyl moiety of N,N-dimethylcarbamate, aliphatic alcohols and thiophenols (Method that is, the 3-methyl-4-nitrophenyl group of C-1).13) N-Alkyl- or N-phenylcarbamates fenitrothion and the 3-methyl-4-methylthio- were prepared by reacting the appropriate phenyl group of f enthion. We found that phenol with alkyl isocyanate or phenyl iso- SK-2 (3-methyl-4-nitrophenyl N,N-dimethyl- cyanate in dry isopropyl ether with triethyl- carbamate) and SK-9 (3-methyl-4-methylthio- amine catalyst or in dry toluene (Method D).1" phenyl N,N-dimethylcarbamate) had a re- The synthesized compounds were purified ap- markable synergistic activity as novel syner- propriately by recrystalization or preparative gists against the OP-resistant rice stem borer. TLC. Yields were from 40 to 90%. Structures This paper deals with the relation of chemical of the compounds were confirmed by GC-MS structures of various noninsecticidal car- (a Shimadzu LKB 9000B GC-MS spectro- bamates to synergistic activity and with their meter) analysis. Their melting points and action mechanism. refractive indices are listed in Tables 2, 3 and 4. MATERIALS AND METHODS The following heterocyclic enols were 1. Insects synthesized by known methods: 2, 6-dimethyl- The following Hata-f and S strains of rice 4-hydroxypyrimidine, 16) 4-hydroxy-6-methyl- stem borers were used. An OP-resistant Hata-f 2-phenylpyrimidine,17) 4-hydroxy-6-methyl-2- strain was obtained from an OP-resistant methylthiopyrimidine,18) 4-hydroxy-6-methyl- Hata strain by selection with fenitrothion for 2-methoxypyrimidine,19) 4-hydroxy-6-methyl- three successive generations. The original 2-methylaminopyrimidine,20) 2-anilino-4-hy- Hata strain was collected at Hata in Soj a, droxy-6-methylpyrimidine,21) 2-N,N-dimethyl- Okayama prefecture in 1983, and maintained amino-4-hydroxy-6-methylpyrimidine,22) and 6- for four years without exposure to insecticides. hydroxy-2-phenyl-3-pyridazinon.23) Other he- A susceptible S strain was collected at Kawa- terocyclic enols, phenols or alcohols used in Journal of Pesticide Science 15 (2), May 1990 177

Table 1 Toxicity of OP insecticides to the Hata- methyl-4-nitrophenyl phosphate, 1.6 mCi/ f and S strains of rice stem borers. mmol, >99% purity) dissolved in 10 ul of ethanol was added, and the mixture was in- cubated at 27C for 30 mm. The detoxication activity of fenitroxon by binding protein and hydrolysis was determined by the method of Konno & Shishido.8) RESULTS 1. Synergistic Activity of Substituted Phenyl N, N-Dimethylcarbamates for Fenitrothion a ) Figures in parentheses indicate 95% confidence against the Hata f Strain of Rice Stem limits. Borers Results are summarized in Table 2. Syner- gism was found in almost all test compounds. this experiments were obtained from com- An unsubstituted phenyl ester of N,N-di- mercial sources. methylcarbamate (1) gave a synergistic ratio of 5.8. The position, type, size and number 3. Toxicity and Synergism Tests of substituents attached to the aromatic Toxicity and synergism tests were conducted nucleus of phenyl N,N-dimethylcarbamate according to the methods described previous- greatly affected synergistic effect for f eni- ly.5,6) Since all of the test carbamates used as trothion. synergists are nontoxic to rice stem borers at In the monosubstituted group, the order of the test dose, synergistic effect is simply ex- the positional effectiveness of synergism for pressed as the following ratio. methyl (2-4), nitro (8-10) and chloro (11-13) Synergistic ratio (SR) substituents was para = meta>ortho. Syner- LD50 of OP insecticide alone gistic activity was weaker in the presence of ortho substituents (2, 8 and 11: SR= 4.3-5.1) LD50 of OP insecticide in mixture than unsubstituted ester (1). Especially, the OP insecticides used in this study were feni- presence of more bulky substituents such as trothion, pirimiphos-methyl and f enitroxon, sec-butyl (6) and isopropoxycarbonyl (19) and Table 1 shows their LD 5o values for the two groups in the ortho-position of ring significantly strains. decreased synergism (SR=1.8 and 0.9, respectively). Esters containing such strongly 4. Enzyme Preparation electron attractive substituents as nitro (9, 10), Whole bodies of 5th instar larvae were chloro (12, 13) and cyano (14) groups in the homogenized (20% w/v) with 1 mM EDTA- meta- or para-position showed a marked 5 mM 2-mercaptoethanol-0.1 M phosphate synergistic activity (SR = 8.2-14) compared buffer, pH 7.4 in an ice bath. The homog- with those containing alkyl, alkoxy, acyl and enate was centrifuged at 105,000 X g at 4C acyloxy substituents (4, 5, 7, 16-18: SR= for 60 min, and the supernatant (soluble frac- 3.0-8.1). Compound 15 with a methylthio tion) was used as an enzyme source of feni- substituent on the para-position was far more troxon detoxication activity. effective than we expected from electronic properties (SR=16). It is well known that 5. Inhibition Study on Detoxication Activity of the methylthio group is easily oxidized by Fenitroxon insects into sulf oxide and sulf one that have The enzyme solution (1 ml) and 10,ul of an strongly electron-withdrawing properties. Thus, inhibitor at several concentrations dissolved it seems that this biotransf ormation is a cause in acetone were preincubated at 27C for 10 for the effective synergism of fenitrothion by min. After the preincubation, 10 ug of compound 15. In electron releasing groups, [Methoxy-14C]fenitroxon (0,0-dimethyl 0-3- the methyl substituent (3) in the meta-position 178 日本農薬学会誌第15巻第2号平成2年5月

Table 2 Properties of substituted phenyl N, N-dimethylcarbamates and their synergistic activities for fenitrothion against the Hata-f strain.

a) Test carbamates which have a strong synergistic activity are named as in parentheses. b) A, the method of Stevens & Beutel.11) C) See MATERIALS AND METHODS.

was relatively effective (SR= 9.2). that of 3,5-, 3,6-, 4,6- and 2,4-combinations In the disubstituted group, substitution in (22, 24, 25, 28, 29: SR = 0.8-5.8). In the 3,4- the 3,4-combinations (21, 23, 27, 30, 31: SR= disubstituted group, a combination of the 6.3-23) gave a higher synergistic activity than electron-attracting group in the Maya-position Journal of Pesticide Science 15 (2), May 1990 179

Table 3 Properties of substituted heterocyclic, naphthyl, benzyl, and aliphatic esters of N, N-dimethylcarbamates and their synergistic activities for f enitrothion against the Data-f strain. 180 日本農薬学会誌第15巻第2号平成2年5月

Table 3 (Continued)

a) Test carbamates that have a strong synergistic activity are named as indicated in parentheses. 1) A , the method of Stevens & Beutel"); B, the method of Baranyovi is et al.12>; C-1, the methods of Sekera et al.") and Gysin et al.14); C-2, A modified method of Sekera et al. 13); (See MATERIALS AND METHODS). C) See MATERIALS AND METHODS.

and the electron-releasing methyl group in the as a 3,5-dimethyl-4-chloro substituent (34) had meta-position was most effective, that is, 3- an excellent effect (SR =11), methyl-4-nitro-phenyl (23, SK-2: SR = 23) and 3-methyl-4-methylthiophenyl (27, SK-9: SR = 2. Synergistic Activity of Substituted Hetero- 22) esters. cyclic, Naphthyl, Benzyl and Aliphatic In the trisubstituted group, the presence of Esters of N, N-Dimethylcarbamates for Feni- ortho-substituents (32, 33) gave a low synergistic trothion against the Hata f Strain activity (SR =1.1 and 5.8, respectively), where- Results are summarized in Table 3. Syner- Journal of Pesticide Science 15 (2), May 1990 181 gism was found in substituted heterocyclic (35- against the Hata-f strain (Table 5). At a 52) and naphthyl (53-55) esters, whereas no 1: 5 or 1: 10 ratio of insecticide: synergist, synergism was found in substituted benzyl excellent synergism was found in all the test (56-58) and aliphatic (59-61) esters. carbamates (SR =188-1061). The synergistic In the heterocyclic esters, the pyrimidine activity of heterocyclic esters for pirimiphos- group with 2,6-substituents (40-45, 47, 49) methyl was higher than that of phenyl esters showed an excellent synergistic activity (SR = as was the case with fenitrothion. Particular- 11-38). Particularly, 2-methylamino-6-methyl ly, SK-102 had the highest synergistic activity (45, SK-104), 2-dimethylamino-6-methyl (47, at the 1: 10 ratio (SR =1061). The synergistic SK-102) and 2-diethylamino-6-methyl (49, activity at the 1: 1 ratio was from 1 /6 to 1 /3 SK-39) substituents on the pyrimidine ring of that at 1: 10 and 1: 5 ratios. gave an excellent effect (SR = 21, 38 and 20, respectively), and SK-102 was the most 5. Synergistic Activity of Substituted Aryl effective as a fenitrothion synergist among the N, N-Dimethylcarbamates for Fenitroxon carbamate compounds studied. In other against the Hata f Strain heterocyclic esters, 2-quinolinyl (38), 3-methyl- Table 6 shows the synergistic activity of 5-isoxazolyl (51, SK-109) and 3-phenyl-5-iso- SK-2, -9, -39, -40 and -102 for fenitroxon, an xazolyl (52, SK-40) esters gave an excellent actual toxicant of fenitrothion, against the synergistic effect (SR =15, 16, and 23, re- Hata-f strain. Excellent synergism was found spectively), whereas compounds 37 and 48 in all the SK compounds (SR = 6.9-12). having a substituent adjacent to the enolic carbon of the ester linkage showed a low 6. Synergistic Activity of Substituted Aryl synergistic effect (SR = 4.1 and 6.3, respec- N,N-Dimethylcarbamates for Fenitrothion tively). against the S Strain In the naphthyl group, 1-naphthyl (53) and Table 7 shows the synergistic activity of 2-naphthyl (54) esters had a relatively high SK-2, -9, -39, -40 and -102 for fenitrothion synergistic activity (SR =13 and 16, respec- against the S strain. Although the SK com- tively), whereas an addition of 2,4-dichloro pounds were excellent synergists against the substituent to 1-naphthyl ester (55) reduced Hata-f strain, no synergism was found against synergism 10-fold (SR= 1.3). the S strain (SR =0.7-1.0).

3. Synergistic Activity of N,N-Diethyl-, N- 7. Inhibition of Binding Protein and Hydro- Alkyl-, N-Phenyl-, N,N-Dimethylthiono- lysis by SK-102 and N,N-Dimethylthiol-carbamates for Effects of a synergist on the two detoxication Fenitrothion against the Hata f Strain systems of fenitroxon by binding protein and Results are summarized in Table 4. N,N- hydrolysis8) were examined with SK-102. Diethyl- (62-71), N, N-dimethylthiono- (92-97), Table 8 shows 150 values of SK-102 against and N,N-dimethylthiol-carbamates (98-100) activities of the binding protein and hydro- (SR =1.0-13) showed synergism, but the ac- lysis responsible for the detoxication of f eni- tivity was 2 to 18 times lower than that troxon in the Hata-f strain. SK-102 strongly of the corresponding N,N-dimethylcarbamates inhibited the protein-binding and hydrolysis of (Tables 2 and 3). On the other hand, N- fenitroxon. methyl-, N-ethyl- and N-phenyl carbamates DISCUSSION (72-91) (SR = 0.6-1.5) showed little synergism. It has been found that various noninsectici- 4. Synergistic Activity of Substituted Aryl dal carbamates, which are synthesized as analog N, N-Dimethylcarbamates for Pirimiphos- synergists on the basis of "synergism theory," methyl against the Hata -f Strain synergize OP insecticides against OP-resistant SK-2, -9, -39, -40, -102, -104 and -109, which rice stem borers. In spite of differences in the were strongly synergistic for fenitrothion, were position, type, size and number of substituents evaluated as synergists for pirimiphos-methyl in the aromatic ring, substituted aryl N, N- 182 日本農薬学会誌第15巻第2号平成2年5月 Journal of pesticide Science 15 (2), May 1990 18 184 日本農薬学会誌第15巻第2号平成2年5月

Table 5 Synergistic activity of substituted aryl N, N-dimethylcarbamates f or pirimiphos- methyl against the Hata-f strain.

a) See Tables 3 and 4. b) See MATERIALS AND METHODS.

Table 6 Synergistic activity of substituted aryl Table 7 Synergistic activity of substituted aryl N, N-dimethylcarbamates for fenitroxon against N, N-dimethylcarbamates for f enitrothion against the Hata-f strain. the S strain.

a) See Tables 2 and 3. a) See Tables 2 and 3. b) Figures in parentheses indicate 95 b) Figures in parentheses indicate 95% confidence c confidence limits. limits. C) See MATERIALS AND METHODS. C) See MATERIALS AND METHODS.

Table 8 155 values of SK-102 against fenitroxon detoxication activities by binding protein and hydrolysis in the Hata-f strain. Journal of Pesticide Science 15 (2), May 1990 185 dimethylcarbamates were usually active as We have demonstrated that the Hata strain synergist. The synergistic activity was signifi- of rice stem borers is highly resistant to OP cantly influenced by carbamate ester linkage insecticides with the aromatic heterocycle such and a carbamate N-substituent. Changing as pirimiphos-methyl or isoxathion, and that carbamate ester linkage to thiol (SC=O) and the highest resistance is found in pirimiphos- thiono (OC=S) reduced synergistic activity methyl having the 2-diethylamino-6-methyl-4- markedly (Table 4). Change from N,N-di- pyrimidinyl group. 6)Therefore, we also studied methyl to N-methyl, -ethyl or -phenyl resulted on heterocyclic enol carbamates. As expected, in a dramatic loss of synergistic activity (Table excellent results were obtained when the 4). Even a small change from an N,N-dimeth- pyrimidinyl moiety (49, SK-39) of pirimiphos- yl to an N, N-diethyl group reduced synergis- methyl or the isoxazolyl moiety (52, SK-40) tic activity remarkably (Table 4). These find- of isoxathion was introduced as the enol ester ings clearly indicate that the N,N-dimethyl- structure of N,N-dimethylcarbamate (Table 3). carbamoyloxy structure is more suitable for a In order to obtain the best fit of pyrimidine synergist than any other carbamic acid struc- groups to the oxon detoxication site, the ring tures. substituent of SK-39 was altered. SK-102, 2- We also found that the synergistic activity dimethylamino-6-methyl-4-pyrimidinyl N,N- disappeared when aryl esters of N,N-dimethyl- dimethylcarbamate (47) was the most effective carbamate changed to straight-chained ali- synergist for fenitrothion (Table 3) and pirimi- phatic esters or benzyl esters (Table 3). phos-methyl (Table 5). The position and character of substituents The rules regarding the structure-activity attached to the phenyl moiety of N,N-di- with substituted phenyl N,N-dimethylcarba- methylcarbamates significantly affected mates also hold for heterocyclic esters. For synergism. From the evaluation of structure- example, the pyrimidine moiety of SK-102 activity correlations in 34 substituted phenyl resembles the phenol moiety of SK-2 in elec- N,N-dimethylcarbamates (Table 2), several tronic properties and the position of sub- rules have become clear, (i) positional effect is stituent on the ring, that is, the nitrogen atom in the order of para=meta>ortho, (ii) electro- in the 1-position of the pyrimidine ring that negative substituents in the para- or meta- acts as a powerful electron attractor cor- position are favorable, (iii) substituents in the responds to the 4-nitro substituent on the ortho-position are far less active, (iv) 3-methyl- phenyl ring, and the 6-methyl corresponds to 4-electronegative substituents are excellent. the 3-methyl substituent. An addition of a Thus, in the phenyl esters tested, SK-2 and methyl group in the 5-position adjacent to the -9 with the phenyl moiety of fenitrothion and enolic carbon (the 4-position of pyrimidine f enthion were most effective as synergists for ring) of SK-102 (47: SR =38) reduced syner- fenitrothion. gistic activity markedly (48, pirimicarb: SR = Why do only such phenyl esters of N,N- 6.3) (Table 3). The low synergistic effect of dimethylcarbamates have an excellent syner- ortho-substituents may be due to the steric gistic activity? In Okayama prefecture, f eni- hindrance weakening the binding of carbamate trothion and fenthion have been primarily to the oxon detoxication site. used for control of rice stem borers since the In 100 carbamate compounds tested, four late 1960s.1) The continuous use of these compounds (SK-2, -9, -40 and -102) showed an insecticides resulted in the selection of OP- excellent synergistic activity at a 1: 10 ratio resistant rice stems borers with oxon detoxica- of insecticide: synergist. Especially, SK-102 tion site (s) that has a strong affinity for the suppressed resistance of the Hata-f strain to structure of 0, 0-dimethyl 0-aryl phosphates fenitrothion and pirimiphos-methyl 38- and corresponding to f enitrothion and f enthion. 1202-fold, respectively. Since synergistic ratios SK-2 and -9 designed for analog synergists of K-2 to fenitrothion and pirimiphos-methyl have aryl groups in common with these against the Hata-f strain are 9 and 410, re- phosphates. This seems to be the reason for spectively (Konno & Shishido, unpublished high synergistic activity of SK-2 and -9. data), SK-102 is 4.2 and 2.6 times more effec- 186 日本農薬学会誌第15巻第2号平成2年5月 tive than K-2, as a synergist for f enitrothion and pirimiphos-methyl, respectively. ACKNOWLEDGMENTS There have been several reports on synergism We thank Dr. F. Tanaka in the Okayama Prefec- between OP insecticides and carbamates. tural Agricultural Experiment Station for the supply Plapp & Valega10) have evaluated nearly 200 of the resistant strain of rice stem borers, and we also noninsecticidal carbamates as synergists for thank Mr. K. Uchiumi in the Institute of Physical carbamates and OP insecticides against several and Chemical Research for the supply of the sus- strains of houseflies. Synergistic activity is ceptible strain of rice stem borers. associated with phenyl esters of N-alkyl and REFERENCES N, N-dialkyl carbamates, but aliphatic esters or unsubstituted carbamates are inactive. 1) F. Tanaka, S. Yabuki & A. Tsuboi: Kinki Phenyl N, N-dibutylcarbamates are able to Chugoku Agric. Res. 64, 60 (1982) enhance the toxicity of Isolan against Isolan-R 2) Y. Manabe, Y. Kono & Y. Sato: J. Takeda Res. Lab. 42, 87 (1983) strains of houseflies 5-fold. Although the 3) T. Konno & O. Kajihara: A ppi. Entomol. Zool. action mechanism of these synergist has not 20, 403 (1985) been investigated, the noninsecticidal car- 4) Y. Konno & T. Shishido: J. Pesticide Sci. 10, bamates appear to act by interfering with the 285 (1985) oxidative detoxication of insecticidal car- 5) Y. Konno, T. Shishido & F. Tanaka: A ppi. bamates. Synergism between OP insecticides Entomol. Zool. 23, 99 (1988) and carbamates have also been reported in the 6) Y. Konno, T. Shishido & F. Tanaka: J. green rice leafhopper, Nephotettix cincticeps,24) Pesticide Sci. 11, 393 (1986) and the smaller brown planthopper, Laodelphax 7) Y. Konno & T. Shishido: J. Pesticide Sci. 12, striatellus.25) However, the synergistic mech- 469 (1987) 8) Y. Konno & T. Shishido: J. Pesticide Sci. 14, anism in these insects have not yet been 359 (1989) clarified. 9) R. J. Kuhr & H. W. Dorough: "Carbamate In the previous paper,8) we reported that the Insecticide," CRC Press, Ohio, p. 282, 1976 synergism of K-2 for f enitrothion was due to 10) F. W. Plapp & T. M. Valega: J. Econ. Entomol. interference with the detoxication of fenitroxon 60, 1094 (1967) by the binding protein and hydrolysis in the 11) J. R. Stevens & R. H. Beutel: J. Am. Chem. OP-resistant rice stem borer. In the present Soc. 63, 308 (1941) studies, we found that S K compounds 12) F. L. C. Baranyovits, R. Ghosh, N. D. Bishop, synergized fenitroxon as well as fenitrothion P. F. H. Freeman & W. G. M. Jones (Imperial Chemical Industries Ltd.): S. African Pat. (Tables 3 and 6). None of these synergists had any significant effect on the toxicity of fenitro- 6701588 (1988); Chem. Abstr. 71, 13137r (1969) 13) A. Sekera, I. Jakubec, J. Kral & C. Vrba: Chem. thion to the S strain of rice stem borers (Table 7). Listy 43, 762 (1952); Chem. Abstr. 47, 12302d These findings indicate that the action mech- (1953) anism of SK compounds is similar to that of 14) H. Gysin, A. Margot & C. Simon (J. R. Geigy, K-2. As shown in Table 8, the protein- A-G): U. S. Pat. 2694712 (1954); Chem. Abstr. binding and hydrolysis activities against feni- 49, 17816b (1955) troxon are markedly inhibited by SK-102. It 15) M. J. Kolbezen, R. L. Metcalf & T. R. Fukuto: is, therefore, concluded that the synergism of J. Agric. Food Chem. 2, 864 (1954) SK-102 is due to the inhibition of the two oxon 16) H. R. Snyder & H. M. Foster: J. Am. Chem. detoxication as is the case with K-2. SK-102 Soc. 76, 118 (1954) has a higher inhibition activity than K-2 when 17) A. Pinner: Berichte 17, 2519 (1884) compared in the I50values.8) 18) J. Stank: Chem. Listy 52, 357 (1958); Chem. Abstr. 52, 11072a (1958) In order to clarify whether SK compounds 19) W. M. Bruce: J. Am. Chem. Soc. 26, 449 (1904) are effective as synergists against combinations 20) T. B. Johnson & K. G. Mackenzie: Am. Chem. of different insects and insecticides, further J. 42, 353 (1909) study is now in progress. 21) T. Matsuka.wa & K. Sirakawa: J. Pharm. Soc. Jpn. 71, 933 (1951) 22) C. G. Overberger & I. C. Kogon: J. Am. Chem. Journal of Pesticide Science 15 (2), May 1990 187

Soc. 76, 1879 (1954) 3-メチル-4-ニトロフェニル基(SK-2)と3-メチル-4-

23) S. D. Breuil: J. Org. Chem. 26, 3382 (1961) メチルチオフェニル基(SK-9)の効果が高かった. ヘテ 24) H. Hama & T. Iwata: Jpn. J. A ppl. Entomol. ロ環では5-フェニル-3-イソキサゾリル基(SK-40)と Zool. 17, 181 (1973) 25) Y. Sasaki & K. Ozaki: Botyu-kagaku 41, 177 2-ジメチルアミノー6-メチルー4-ピリミジニル基(SK- (1976) (in Japanese) 102)の効果が高かった. とくにSK-102の共力効果はきわめて高く, ピリミホスメチルに対する1202倍の抵

抗性は感受性レベルにまで減少した. アリールーNろN匹ジ要約エチルー, -N, NLジメチルチオー,-N;NLジメチルチオー

有機リン剤抵抗性二力メイガに対する殺虫共力ルカーバメートの共力効果は, アリール理Nしジメチル

剤, アリールN, N-ジメチルカーバメートカーバメートの1/18から1/2であった. アリール-N-

昆野安彦, 宍戸孝メチル-, -NV-エチルー, -jNLフェニルカーバメートやア

100種類のカーバメート系化合物を合成し, 有機リンリール基を持たない脂肪族系のN, Nしジメチルカーバメ

剤に混合したときの有機リン剤抵抗性ニカメイガに対すートには共力効果がなかった . またSK-2, -9, -40およる共力効果を検討した. その結果, アリール(ベンゼンび-102は感受性系統のニカメイガには共力効果を示さ

環とヘテロ環を含む)NろNLジメチルカーバメートに高なかった. SK-102のフェニトロチオンに対する共力機

い共力効果のあることが判明した. ベンゼン環の置換基構はフェニトロオクソンを解毒するbinding proteinと

の効果は, パラ≒ メタ＞オルソの順であった. とくに加水分解作用の強い阻害に基づくことが判明した.