Brief Market Analysis of Spirotetramat

Spirotetramat is a ketone‑acid‑based insecticide and acaricide developed by Bayer. Its chemical name is (E)-3-(2,5‑dimethylphenyl)-8‑methoxy‑2‑oxo‑1‑azaspiro[4.5]dec‑3‑en‑4‑yl ethyl carbonate, with CAS registry number 203313‑25‑1.

This product is a lipid‑synthesis inhibitor that induces toxicity and death in insects by blocking the synthesis of their lipids. It offers long residual activity and provides effective control of a wide range of piercing‑sucking pests and mites. Its mode of action is unique, with no cross‑resistance to currently available insecticides. Spirotetramat exhibits systemic properties, translocating both upward and downward throughout the plant to reach leaf surfaces and bark; this distinctive systemic behavior helps protect emerging stems, leaves, and roots.

1.     Mechanism of action of spirotetramat ：

Spirotetramat, along with Bayer’s insecticidal and acaricidal products spirodiclofen and spiromesifen, belongs to the same class of diketone acid compounds and shares a similar chemical structure and mode of action. These compounds are inhibitors of acetyl‑CoA carboxylase (ACC); by suppressing ACC activity, they disrupt fatty acid biosynthesis in pests, thereby achieving pest control.

It also exhibits excellent efficacy against piercing‑sucking pests such as mealybugs, aphids, and leafhoppers, and is suitable for a wide range of crops, including cotton, soybeans, citrus, fruit trees, potatoes, and vegetables. After entering the plant, spirotetramat is rapidly hydrolyzed into its enol form, spirotetramat‑enol, as shown in the figure below:

Spirotetramat is, to date, the only modern insecticide with bidirectional systemic translocation in both the xylem and phloem. This unique systemic movement ensures more thorough control of pests, while its long residual activity provides effective protection for up to eight weeks.

2. Brief Description of the Synthetic Route

Spirotetramat is synthesized via the reaction of the key intermediate 2,5-dimethylphenylacetyl chloride with a 1,4‑substituted cyclohexylamine, and it can be prepared through two main synthetic routes.

Route 1: Chiral‑pool synthesis—starting from cis‑8‑methoxy‑1,3‑diazaspiro[4.5]decane‑2,4‑dione, the hydrolysis‑derived aminocarboxylic acid is first esterified, followed by amidation and ring closure; the resulting hydroxy ester is then subjected to esterification to afford the target compound. The reaction scheme is as follows:

Method 1 involves complex starting materials but eliminates the need for chiral resolution of the final product; Method 2 features a relatively straightforward synthetic route, yet requires chiral resolution of the final product (only the cis‑isomer of spirotetramat is biologically active).

3. Registration Status

  In 2007, Bayer first launched spirotetramat at the Crop Protection Conference in Glasgow, UK. That same year, the product was initially approved for registration in Tunisia. In 2008, it was registered and launched in the United States, Canada, Austria, New Zealand, Morocco, and Turkey; in 2009, it gained registration and market approval in Brazil, South Africa, the Netherlands, Australia, and Mexico; in 2010, it was registered and launched in Japan; and in March 2011, it was registered and launched in China. Since its registration in 2007 and market launch in 2008, spirotetramat has experienced rapid market expansion.

Since the expiration of Bayer’s spirotetramat patent on July 22, 2017, several domestic manufacturers have successively applied for active‑ingredient registration of spirotetramat. At present, a total of 15 companies—including Bayer—such as Qingdao Zhongda, Hebei Xingbai, Lianyungang Liben, Jiangsu Zhongqi, Shandong Hailir, Shanghai Yuelian, and Hebei Weiyuan, hold active‑ingredient registration for spirotetramat.

Its primary registered formulation is a 22.4% suspension concentrate of spirotetramat, and Shaanxi Meibang holds the only registration in China for a 50% water-dispersible granule of spirotetramat. In terms of combination formulations, the main ones available domestically are:

Spirotetramat 11% + Buprofezin 22% Suspension Concentrate

Spirotetramat 11% + Thiamethoxam 11% Suspension Concentrate

Spirotetramat 30% + Etoxazole 15% SC

Spirotetramat 25% + Pymidone 50% Water-Dispersible Granules

Spirotetramat 8% + Chlorpyrifos 25% suspension concentrate, etc.

Typically, this is achieved by formulating with nicotinoids or other acaricides to enhance synergistic effects with fast‑acting insecticides and acaricides, thereby providing crops with both protective and long‑lasting mite‑control efficacy.

Is it equivalent to the spirotetramat registered with Bayer in China?

At present, although 13 domestic companies have registered the technical-grade active ingredient of spirotetramat, Bayer’s expired patent covers only its cis–trans isomer mixture; the patent on the cis isomer, which exhibits insecticidal activity, has not yet expired. Bayer’s technical‑grade product contains more than 98% active ingredient, resulting in superior insecticidal efficacy. Moreover, Bayer has established mature formulation‑production processes, and its commercial formulations demonstrate higher safety and greater insecticidal performance compared with domestically produced products.

4. Patent Status

On July 22, 2017, the Chinese compound patent for Bayer’s spirotetramat, Patent No. ZL97198554.5, expired. However, this patent covered a mixture of cis–trans isomers, while the patent for the cis isomer—the form that actually exhibits insecticidal activity—did not expire until 2023. On the eve of the global first registration of spirotetramat, Bayer filed multiple patents related to suspension concentrates. Following the full market launch of the single‑active‑ingredient product, Bayer promptly pursued patent protection for formulated combinations, securing patents on spirotetramat–insecticide mixtures; for example, its combination with flupyradifurone remains protected until sometime between 2029 and 2030.

5. Market Conditions

Bayer’s spirotetramat business has been growing rapidly worldwide, with global sales expected to reach €300 million in 2020. In recent years, it has also posted double-digit growth in the Chinese market. In 2017, combined sales of formulated products and technical-grade active ingredient exceeded RMB 150 million at end‑user prices, delivering strong performance across numerous markets targeting pests with resistance concerns.

The issues at hand: 1. Poor rapid efficacy and relatively high cost.

For conventional acaricides such as etoxazole, amitraz, abamectin, emamectin benzoate, and pyridaben, awareness of the need for protective acaricides remains low in the Asia-Pacific region and certain Latin American countries. Farmers tend to rely on fast‑acting, knockdown‑type acaricides during explosive outbreaks of adult mites, while overlooking the use of long‑lasting protective agents. Moreover, traditional acaricides enjoy a significant price advantage, making them easier for distributors to promote.

At present, the long‑lasting protective acaricides available are all spirocyclohexenyl ketone‑type compounds. As mite control becomes increasingly sophisticated and emphasis shifts toward ovicidal products, and with resistance to conventional acaricides steadily rising, spirotetramat is poised to emerge as an optimized alternative to traditional acaricides, boasting promising prospects for widespread adoption.

The problem at hand! 2. Drug resistance has already emerged.

Since its registration and use, spirotetramat has been widely applied in the field to control agricultural pests such as mealybugs, whiteflies, and red spider mites. Both domestically and internationally, resistance-monitoring studies have been conducted on the target pests of this active ingredient.

China has also detected a potential risk of resistance in populations of the tobacco whitefly and the brown planthopper in Hubei Province, driven by sustained selection pressure from insecticides. Although no significant resistance has yet been observed, drawing on the precedent set by chlorantraniliprole, overreliance on highly effective new compounds will inevitably lead to severe resistance. The underlying mechanism of resistance is primarily a reduction in susceptibility to the active ingredient, resulting from mutations in the acetyl‑CoA carboxylase (ACC) gene.

Additionally, it is worth noting that:

Spirotetramat, along with other insecticides belonging to the ketone acid class, poses a significant risk of cross‑resistance due to their similar sites of action.

Spirotetramat exhibits a moderate to low level of cross‑resistance with several insecticides commonly used in the field to control the tobacco whitefly and the hibiscus mealybug (Phenacoccus solenopsis), including imidacloprid, sulfoxaflor, methomyl, acephate, lambda‑cyhalothrin, fenvalerate, chlorpyrifos, profenofos, and bifenthrin.

Moreover, it exhibits high levels of cross-resistance to fenvalerate, bifenthrin, and abamectin.

The main market trends for spirotetramat products are as follows:

Bayer is promoting spirotetramat as a next‑generation, long‑lasting acaricide for fruits, vegetables, and minor crops; as its patent expires, the company will gradually shift its focus to developing formulated combination products. When used in conjunction with the fast‑acting insecticides imidacloprid and flonicamid on these same crop segments, it delivers a synergistic effect, and the overall market outlook remains positive.

For domestic enterprises, it is essential to monitor the usage patterns of mainstream acaricides in key crop segments within target markets. In response to resistance and mite outbreaks, they should develop spirotetramat as a protective, long‑lasting active ingredient, as well as complementary formulations to complement existing acaricides.

The biocidal applications of spirotetramat will be progressively developed, encompassing uses in public health, turf and horticulture, veterinary medicine, and plantation protection, while its non‑agricultural applications are expected to expand.

6. Summary

In recent years, the market has placed increasingly stringent demands on the safety and environmental compatibility of insecticides. Consequently, a growing number of novel insecticides—praised for their high efficacy and safety—are gaining widespread acceptance. This underscores the continued need for insecticides that can effectively delay the emergence of resistance and target new modes of action. At present, field populations of pest insects exhibit only low levels of resistance to spirotetramat, and this innovative insecticide is poised to play a pivotal role in the management of agricultural pests. However, as application rates rise and its use expands, resistance among agricultural pests is likely to increase.

Going forward, the focus of its formulation development will be on formulating traditional fast‑acting insecticides to enhance efficacy and mitigate the risk of resistance. At the same time, it will explore applications in non‑agricultural sectors, such as public health products; this approach not only simplifies the registration process compared with agricultural uses but also helps expand market share to the greatest extent possible.

Drawing on the successful market introductions of spiromesifen and spirodiclofen, we will refine the market‑entry strategy for spirotetramat to mitigate competition from similar products.

References:

1. Research Progress on Resistance of Agricultural Pests to Spirotetramat Qian Yunong 2018.

2. Currently Registered Spirotetramat Products in China – Agricultural Market Information, 2017

3. Development of Spirotetramat, a Novel Systemic Insecticide with Bidirectional Translaminar Activity — Zhang Qingkuan, 2009

4. The spirotetramat market is booming; now more than ever, it’s crucial to stay true to fundamentals. Gu Qianqian, September 2018.

5. Analysis of the Current Patent Landscape for Spirotetramat, an Insecticide and Acaricide — Yang Linlin, Duan Jie, 2016

6. Spirotetramat: Pesticide Varieties Whose Patents Expired from 2016 to 2020 — Zhang Meifeng, Lü Xiu Ting, 2014

7. Synthesis and Process Route Study of Spirotetramat Li Du 2012

We also thank Qin Enhao for providing the materials.