2025 年 50 巻 3 号 p. 96-101
Oxazosulfyl, a novel insecticide originally discovered and developed by Sumitomo Chemical Co., Ltd., belongs to a new chemical class, the sulfyl group, structurally characterized by its ethylsulfonyl moiety. It exhibits excellent control against a broad range of major rice insect pests, including Coleoptera, Hemiptera, Lepidoptera, and Orthoptera, through nursery-box application. With a novel structural backbone and mode of action, this insecticide is classified by the Insecticide Resistance Action Committee as the sole member of novel code 37, vesicular acetylcholine transporter inhibitor. A substantial number of field studies in rice paddy fields have demonstrated that oxazosulfyl, registered in Japan in April 2021 as ALLES® granules, is highly effective against populations that have developed reduced sensitivity or resistance to existing insecticides. Given these favorable properties, oxazosulfyl is expected to contribute to the management of insecticide resistance, the reduction of agricultural chemical use, labor savings, and sustainable agriculture as a next-generation insecticide.
Rice continues to be the most important cultivated crop in Japan, where a wide variety of insect pests belonging to diverse taxonomic orders negatively affect the quality and yield of rice production. Today, many of these insect pests are controlled through the nursery box application of systemic insecticides, which can reduce the number of insecticide applications in paddy rice fields and confer labor savings to farmers. In the 1990s, neonicotinoid and phenylpyrazole insecticides were commercialized and rapidly accepted by farmers as long-lasting insecticides for nursery box application, as represented by imidacloprid (Insecticide Resistance Action Committee [IRAC] code 4A) and fipronil (2B), respectively. However, a reduction in the efficacy of these representative insecticides has been reported since 2005 and insecticide resistance has become an urgent issue in the crop protection industry. For example, brown planthoppers, Nilaparvata lugens, are resistant to neonicotinoid insecticides such as imidacloprid;1) white-backed planthoppers, Sogatella furcifera, to fipronil;1) small brown planthoppers, Laodelphax striatellus, to neonicotinoid insecticides and fipronil;2) and rice leaf beetles, Oulema oryzae, to neonicotinoid insecticides3) and fipronil.4) To control these resistant insect pests, newer insecticide molecules belonging to different chemical classes with distinct modes of action have been discovered and registered for nursery box applications, such as diamide insecticides (IRAC code 28) and triflumezopyrim (4E). However, the main modes of action are limited to IRAC codes 1A, 2B, 4A, 4E, 4F, 5 and 28 today. Therefore, the exploration of novel insecticides with new modes of action continues to be a central topic considering the long-term viewpoint of sustainable insecticide resistance management.
Oxazosulfyl (Fig. 1) is a novel insecticide discovered and developed by Sumitomo Chemical Co., Ltd.5,6) It belongs to a new chemical class, the “sulfyl” group, structurally characterized by its ethylsulfonyl moiety. The discovery of this chemical class originated from the intensive exploratory study of our own chemical library,7) in which Compound 1 (Fig. 2) attracted attention because of its insecticidal activity against adults and nymphs and unique chemical structure. An initial study of the structure–activity relationship of Compound 1 and its analogs showed that the ortho-substitution of the methylthio-group moiety on the benzene ring of Compound 1 is very important for insecticidal activity rather than the meta- and para-substitutions. The activity was improved by substituting the methylsulfanyl moiety on the benzene ring of Compound 1 with an ethylsulfonyl moiety (Compound 2). Replacing the benzene ring of Compound 2 with a pyridine ring (Compound 3), after the elucidation of several 5- and 6-membered aromatic and non-aromatic ring substitutions (e.g., thiazole, thiophene, and cyclopentene), further improved the activity. Thereafter, the imidazopyridine ring of Compound 3 was converted to a variety of 6-5 fused heterocycles (e.g., oxazolopyridine, thiazolopyridine, imidazopyridine, benzimidazole, and benzothiazole); compounds with a benzoxazole ring exhibited potent insecticidal activity.
Our further optimization study showed the excellent performance of compounds with a trifluoromethylthio structure at the 5-position of the benzoxazole ring (Compounds 5, 6, and oxazosulfyl) in terms of insecticidal spectrum and systemic action. To compare the practical efficacy of the most promising candidate molecules (i.e., Compound 6 vs. oxazosulfyl) out of the three, multiple field trials were conducted. The sulfonyl compound (oxazosulfyl, n=2) was more effective at controlling insect pests at a lower density than the sulfinyl compound (Compound 6, n=1); the difference was more prominent when the granules of the two compounds were applied during the sowing of rice seeds onto the nursery box. Consequently, oxazosulfyl was selected as the compound for commercialization.
Table 1 shows the median lethal concentration (LC50) and median lethal dose (LD50) values of oxazosulfyl against multiple insect pest species belonging to different taxonomic orders. The baseline insecticidal activity of oxazosulfyl is comparable to that of each standard reference product against sucking and chewing pests.8) Our laboratory bioassay using field-collected populations of planthoppers showed that the insect pests tested were similarly susceptible to oxazosulfyl, whereas their resistance ratios to imidacloprid were 568.4 in N. lugens and 30.2 in L. striatellus and those to fipronil were 71 in S. furcifera and 16.5 in L. striatellus (Fig. 3), indicating no cross-resistance to oxazosulfyl.8) This result conforms to the recent decision by the IRAC, which classified the mode of action of oxazosulfyl into the novel code 37, vesicular acetylcholine transporter (VAChT) inhibitor.9)
| Species | Stage (application)a) | LC50b) or LD50c) | Oxazosulfyl | Imidacloprid | Chlorantraniliprole |
|---|---|---|---|---|---|
| Hemiptera | |||||
| Brown planthopper, Nilaparvata lugens | Nymph, 3rd (f) | LC50 | 0.41 | 0.19 | >500 |
| Small brown planthopper, Laodelphax striatellus | Nymph, 3rd (f) | LC50 | 0.61 | 0.18 | >500 |
| White-backed planthopper, Sogatella furcifera | Nymph, 3rd (f) | LC50 | 0.82 | 0.17 | >500 |
| Green rice leafhopper, Nephotettix cincticeps | Nymph, 3rd (f) | LC50 | 0.092 | 0.012 | 15 |
| Lepidoptera | |||||
| Rice stem borer, Chilo suppressalis | Larva, 2nd (f) | LC50 | 0.20 | 28 | 0.076 |
| Rice leafroller, Cnaphalocrocis medinalis | Larva, 2nd (f) | LC50 | 0.27 | 10 | 0.025 |
| Coleoptera | |||||
| Rice leaf beetle, Oulema oryzae | Adult (t) | LD50 | 0.0040 | 0.0043 | — |
a) f: foliar spray, t: topical application, b) mg a.i./L, c) µg a.i./insect.
The phosphor imaging assay using radiolabeled oxazosulfyl by soil drench application illustrated the systemic movement of oxazosulfyl into the whole plants of rice seedlings, including roots, stems, and leaves, 3 days after treatment (Fig. 4A). When the insect pest N. lugens was released onto the aerial parts of rice plants 3 days after drench application, the mortality quickly increased from 1 day after the release of the insects; the subsequent increase in mortality due to treatment with oxazosulfyl was similar to that with imidacloprid against the susceptible strain of N. lugens (Fig. 4B). The rate of lethal activity of oxazosulfyl did not change even against the field-collected population of N. lugens, against which imidacloprid was completely ineffective compared with the control (Fig. 4B). These results show that oxazosulfyl can systemically protect rice plants against insect pests promptly after soil application.
Our careful observation of symptoms using a macro video recording system showed that all insect pests (O. oryzae, L. striatellus, N. lugens, and rice grasshopper Oxya yezoensis) treated with oxazosulfyl exhibited non-excitatory reactions and very slow body movements followed by paralysis, without reacting to direct stimuli, and abnormally dropped from the plants. After dropping onto the water surface of the paddy field, although the insects were barely alive, their movement was so limited that they were easily consumed by natural predators. The treated insect pests were also unable to perform their regular life activities, such as sucking, feeding, mating behavior, and oviposition, eventually reaching death; therefore, the treated plants were protected from direct damage and virus transmission by pests and the reproduction of pests on their surface.10)
Our in-house field experiment, in which a susceptible strain of N. lugens was released periodically onto the rice plants to simulate natural infestation (i.e., three releases at 2-week intervals from 35 days after transplanting), showed that the rice plants treated with oxazosulfyl through nursery box application were protected from the damage of N. lugens, whereas the adjacent untreated plots showed devastating damage, such as hopper burn (Fig. 5), indicating the long-lasting efficacy of oxazosulfyl under natural field conditions. Figure 6 shows a representative result of an external field trial in which oxazosulfyl controlled the resistant populations of N. lugens under practical conditions. In this trial, conducted in Kagoshima Prefecture, the natural population of N. lugens was not effectively suppressed by any of the nursery box applications of pymetrozine, fipronil, or imidacloprid; however, it was maintained at a lower density for a long period by the nursery box application of oxazosulfyl at sowing and transplanting. Similarly, oxazosulfyl showed excellent performance in controlling natural populations of other pest species that also display reduced sensitivity to existing products, such as S. furcifera in Kagoshima,10) L. striatellus in Ibaraki,10) and O. oryzae in Hokkaido.10)
Table 2 lists the official efficacy trials conducted by the Japan Plant Protection Association between 2016 and 2020 for the purpose of registering granules containing 2.0% oxazosulfyl in Japan. A high level of practically acceptable efficacy was confirmed in these official trials against a broad range of insect pests in diverse taxonomic orders using several different application timings (i.e., before sowing the rice seeds onto bed soil, at sowing, and at transplanting), with no cases of crop injury. Thereafter, oxazosulfyl was registered as “ALLES® granule” containing 2.0% (w/w) oxazosulfyl (Fig. 7) on April 21, 2021 in Japan.
| Insect pest species | Efficacya) |
|---|---|
| Hemiptera | |
| Brown planthopper, Nilaparvata lugens | +++ |
| Small brown planthopper, Laodelphax striatellus | +++ |
| White-backed planthopper, Sogatella furcifera | +++ |
| Green rice leafhopper, Nephotettix cincticeps | +++ |
| Black rice bug, Scotinophara lurida | +++ |
| Lepidoptera | |
| Rice stem borer, Chilo suppressalis | +++ |
| Rice leafroller, Cnaphalocrocis medinalis | +++ |
| Rice green caterpillar, Naranga aenescens | +++ |
| Rice skipper, Parnara guttata | +++ |
| Coleoptera | |
| Rice leaf beetle, Oulema oryzae | +++ |
| Rice water weevil, Lissorhoptrus oryzophilus | +++ |
| Orthoptera | |
| Rice grasshopper, Oxya yezoensis | +++ |
| Diptera | |
| Smaller rice leaf miner, Hydrellia griseola | ++ |
| Rice stem maggot, Chlorops oryzae | ++ |
a) Expressed by the average of index values of the trials results (excellent=3, good=2, inferior=1 and poor=0), and three pluses “+++” stands for the average value is 2 or more, while two pluses “++” for 1 or more but less than 2.
The discovery of new chemical classes and development of new molecules with novel modes of action represent remarkable advances underlying the growth of the crop protection industry. The “sulfyl” chemical group and its first-in-class molecule, oxazosulfyl, with a new mode of action, VAChT inhibition (IRAC code 37), is a typical example of such industrial achievement. Owing to its favorable characteristics, such as (i) broad insecticidal spectrum covering diverse taxonomic orders, (ii) resistance-breaking activity against difficult-to-control insect pests, and (iii) high suitability for labor-saving nursery box application, the authors anticipate that oxazosulfyl, as a next-generation insecticide, will contribute to regenerative and sustainable agriculture, by reducing insecticide use and any associated environmental impact, and insecticide resistance management.
We would like to thank all concerned parties in the Japan Plant Protection Association and Local Incorporated Administrative Agencies and researchers at the Prefectural Research Institutes and Universities for their valuable suggestions, discussions, and advice regarding product development. The authors are also grateful to the employees of Sumitomo Chemical Co., Ltd., who have been engaged in the discovery and development of oxazosulfyl, for their continuous support and contributions to the project. We give special gratitude to the officers and committees involved in the Pesticide Science Society of Japan for their review and discussion to support our nomination for this Society Award.
