Weed control method

Abstract

The present invention relates to a method of controlling the growth of monocotyledonous weeds that are resistant to ACC enzyme-inhibiting herbicides other than a compound of formula (I) at a locus, said method comprising applying to the locus a herbicide composition comprising a compound of formula (I).

Description

[0001] Herbicides that inhibit acetyl-CoA carboxylase (ACC enzyme) were introduced in the mid-1970s and are now widely used to control grass (monocot) weeds in many crops, including, for example, small grain cereals and dicotyledonous crops such as rice and soybean. Given that ACC enzyme-inhibiting herbicides (ACC enzyme herbicides - HRAC group 1) facilitated post-emergence management of grass weeds and offered a significant improvement over then-common selective grass weed control methods, they were quickly adopted. However, over time, extensive and repeated use of ACC enzyme herbicides led to resistance development in major grass weed species. Currently, there are numerous records of resistance to ACC enzyme herbicides in grass weeds, particularly in the genus *Lolium* (*Lysimachia*). Lolium ), see wheatgrass genus ( Alopecurus ) and oat genus ( Oats Resistance issues are particularly prominent in species.

[0002] Therefore, there is a need for alternative agricultural methods that can provide adequate control over these problematic monocotyledonous weeds resistant to currently available ACC enzyme-inhibiting herbicides (ACC enzyme-resistant weeds). Unexpectedly, it has now been found that certain ACC enzyme-inhibiting herbicides previously disclosed in WO 2019 / 158666 provide very good control over such ACC enzyme-resistant weeds. Therefore, according to the present invention, a method is provided for controlling the growth of monocotyledonous weeds resistant to ACC enzyme-inhibiting herbicides other than those having formula (I) in a site, the method comprising applying a herbicide composition comprising a compound having formula (I) to the site.

[0003]

[0004] Compounds having formula (I) are known from WO 2019 / 158666 and provide effective control of problem weeds in crops, especially cereal crops. Compounds having formula (I) are also known as 3-acetyl-9-[2,6-dimethyl-4-(1-propyn-1-yl)phenyl]-10-hydroxy-3-azaspiro[5.5]undec-9-en-8-one, with CAS number 2374705-11-8. Compounds having formula (I) may exist in alternative forms, as described below as compound (Ia):

[0005]

[0006] Also known as 3-acetyl-9-[2,6-dimethyl-4-(1-propyn-1-yl)phenyl]-3-azaspiro[5.5]undecane-8,10-dione, with CAS number 2374704-95-5. This invention is based on the finding that compounds having formula (I) (or (Ia)) are particularly effective in controlling monocotyledonous weeds resistant to ACC enzyme-inhibiting herbicides.

[0007] The term "site" is simply understood to refer to the location where ACC enzyme-resistant monocotyledonous weeds are present. Examples include gardens, paths, and railway tracks, but more commonly, a site will be a crop-cultivated area, such as a field. For the avoidance of ambiguity, it should be understood that a site may further include other weeds, including those susceptible to ACC enzyme herbicides. When the site is a crop-cultivated area, the method of the present invention has broad applicability in controlling monocotyledonous ACC enzyme-resistant weeds in a variety of crop plants. For example, the herbicide composition can be applied pre-planting (before the crop is planted in the field) to control monocotyledonous ACC enzyme-resistant weeds in a variety of crops subsequently planted at the site, including, for example, corn, cereal crops, cotton, and soybean crops. It should be understood that crop plants may optionally contain herbicide tolerance and / or insect tolerance and / or nematode tolerance traits. Furthermore, it should be understood that some monocotyledonous crop plants (e.g., cereal crops) are inherently resistant to compounds having formula (I), and therefore, in such cases, the herbicide composition can be applied while crop plants are present at the site. Such application can be carried out before emergence (where the crop has been planted at the site but has not yet emerged) or after emergence (or "foliar spraying," where the crop has already emerged at the site). It should be understood that a combination of pre-planting, pre-emergence, and post-emergence applications may be used, depending on the grower's specific needs.

[0008] Therefore, in a preferred embodiment of the invention, a method is provided in which the site further comprises cereal crops, and wherein the method selectively controls the growth of ACC-resistant monocotyledonous weeds at the site. Examples of such cereal crops include wheat, including its spring and winter varieties; and barley, including its spring and winter varieties, durum wheat, rye, and triticale. Wheat is particularly preferred, and includes herbicide-resistant cereal crops such as Clearfield™ wheat.

[0009] Several ACC enzyme herbicides are now commercially available to help growers combat grassy weeds, and these herbicides include, for example, cyclohexanediones (“Dim”), such as clethodim, thiamethoxam, and pyranofibrate; aryloxyphenoxypropionates (“Fop”), such as quizalofop-p-ethyl, haloxyfop-methyl, cyhalofop-butyl, quizalofop-butyl, and quizalofop-ethyl; and “Den”, such as clodinafop-propionate. Appropriate dose-response comparisons are used to characterize ACC enzyme-resistant weeds. Such weeds can be classified into target-based mechanisms and non-target-based mechanisms. Non-target mechanisms (NTSR) are, for example, metabolic-based resistance mechanisms that can be mediated, for example, via cytochrome p450 and / or glutathione S-transferase metabolism. The method of this invention can be used to control monocotyledonous ACC enzyme-resistant weeds characterized by resistance at target sites and / or non-target sites, and is particularly effective in controlling weeds resistant to various FOP, DIM, and DEN ACC enzyme herbicides. NTSR ACC enzyme-resistant weeds can also exhibit tolerance to herbicides of other modes of action, such as acetyllactate synthase (ALS) inhibitory herbicides (HRAC group 2).

[0010] Genetic studies have demonstrated that resistance to ACC enzyme herbicides can be accumulating through target site mutations within the ACC enzyme, and the method of this invention is particularly suitable for controlling monocotyledonous ACC enzyme-resistant weeds characterized by such target site resistance. Target site resistance is caused by a single amino acid change in the carboxyltransferase domain of the ACC enzyme. Many early resistance studies used *Alopecurus aequalis* (large spikelet *Alopecurus aequalis*). Alopecurus myosuroides This is done through [the process], therefore individual amino acid variations (although typically conserved across species) are usually observed based on plastids in the genus *Alopecurus* (*Alopecurus*). Alopecurus The ACC enzyme sequence was used for characterization. Those skilled in the art are familiar with sequence alignment software that can be used to identify the corresponding amino acids in other species.

[0011] Therefore, seven distinct single point mutation sites conferring resistance have now been identified in the ACC enzyme: Ile1781 (I1781); Typ1999 (W1999); Typ2027 (W2027); Ile2041 (I2041); Asp2078 (D2078), Cys2088 (C2088), and Gly2096 (G2096). Furthermore, at least 14 allelic variants are associated with resistance: I1781L / V / A / T; W1999C / L / S; W2027C; I2041N / V; D2078G, C2088R, and G2096A / S. It is further understood that species can be homozygous or heterozygous for the resistance trait. Compounds of formula (I) are expected to also effectively control weeds containing other target site mutations in the ACC enzyme. Those skilled in the art will understand that the observed level of resistance will depend in particular on the specific herbicide, the recommended field rate, the weed species, the plant growth stage, specific amino acid variations and gene copy number, and the mutant ACC enzyme allele.

[0012] According to the International Database of Herbicide-Resistant Weeds (www.weedscience.org), as of 2022, more than 250 unique cases of ACC enzyme-resistant weeds have been reported, including more than 50 unique cases of clodinafop-propargyl-resistant weeds. These include species of the genus *Alopecurus* (…). Alopecurus sp. (For example, the large ear of wheat ( Alopecurus myosuroides ), species of the genus Apila ( Apera sp. (For example, Apira grass ( Open ear of wind ), species of the genus Oat ( Oats sp. (For example, wild oats) Wild oats ), unreal wild oats ( Barren oats ), species of the genus *Brucea* ( Brachypodium sp. (For example, *Bruguiera gymnorhiza* () Brachypodium distachyon ), species of the genus *Lycium* ( Lolium sp. (For example, perennial ryegrass) Perennial ryegrass ), multiflora ryegrass ( Lolium multi-flowered Persian ryegrass ( Apricot Lolium ) and stiff ryegrass ( Rigid lolium ), species of the genus *Gnaphalium* ( Phalaris sp. (For example, small sedge ( Lesser Phalaris ), Qiqi grass ( Phalaris paradoxa ), species of the genus Po ( Poa sp. (For example, Kentucky bluegrass) Annual grass ), species of the genus *Clerodendrum* ( Polypogon sp. (For example, *Clerodendrum trichotomum*) Polypogon fugax )) and species of the genus *Setaria* ( Setaria sp.(For example, foxtail grass) Setaria green Even more preferably, the method of the present invention is used to control ACC enzyme-resistant *Alopecurus* species (e.g., *Alopecurus macrospinipes*), *Oat* species (e.g., wild oats, unfruited wild oats), *Rhizophora* species (e.g., perennial ryegrass, multiflora ryegrass, Persian ryegrass, and stiff ryegrass), *Gnaphalium* species (e.g., small gnaphalium, scabra), or *Setaria* species (e.g., foxtail), particularly in cereal crops. In many cereal-growing areas, ACC enzyme herbicides are commonly used to control grassy weeds. However, resistance to ACC enzyme herbicides has now been widely reported, and the resistance problem is expected to worsen further due to intensification and the lack of alternative solutions. The method of the present invention is particularly suitable for controlling ACC enzyme-resistant weeds, especially clodinafop-propargyl-resistant weeds, and especially those weeds containing the I1781, W2027, D2078, and / or C2088 mutations. ACC enzyme-resistant weeds controlled by the method of the present invention can also be resistant to non-ACC enzyme herbicides (such as glyphosate and / or acetyllactate synthase (ALS) inhibitors).

[0013] In the method of the present invention, compounds having formula (I) (or formula Ia) can be applied to the site at a rate of 1 to 500 g / ha. The actual application rate will depend on many considerations, including, for example, the time of application, the ACC enzyme-resistant weeds to be controlled, and the growth stage. For pre-planting application, a typical application rate may be 25 to 500 g / ha, more preferably 100 to 400 g / ha; for post-emergence application, a typical application rate may be 25 to 200 g / ha. It is envisioned that compounds having formula (I) be applied to the site in multiple applications, for example, in any given growing season, 200 g / ha may be applied to the site in the following manner: a single application of 200 g / ha or an application of 2 x 100 g / ha, etc. It should be further understood that the herbicide composition used in the method of the present invention may further comprise one or more additional pest control agents, such as herbicides, fungicides, insecticides, and / or nematicides. In a preferred embodiment of the invention, the herbicide composition further comprises one or more herbicides selected from the group consisting of sulfadiazine, mesosulfuron-methyl, and diflubenzuron. The herbicide composition may also comprise additional ACC enzyme-inhibiting herbicides, such as quizalofop-p-ethyl (including quizalofop-p-ethyl), haloxyfop-methyl (including haloxyfop-p-ethyl), and / or clodinafop-propargyl. The composition may also comprise a safener, such as quizalofop-p-ethyl or pyrazosulfuron-methyl. The composition may also contain adjuvants, such as tri(2-ethylhexyl) phosphate (TEHP), methylated rapeseed oil adjuvants such as Adigor®, ethoxylated sorbitol such as Tween® 20 and Tween® 80, and fatty alcohol ethoxylates such as Emulsogen® MTP090 (CAS 68002-96-0) and Marlox RT 64 (CAS 68002-96-0). Other tank-mix adjuvants, such as Assist and Ochima®, may also be used.

[0014] biological example

[0015] Various populations of *Lycium oryzae* were used in the study, with each homogeneous population characterized as containing one of the mutations known to be associated with resistance to ACC enzyme herbicides (I1781L, W2027C, D2078G, C2088R). A susceptible population, which was the reference population for the RF, was also included. Seeds from each population were sown in pots of standard soil. For each treatment, three replicate pots (one inch per pot, containing 20 plants) were sprayed at the 2–3 leaf stage. Clotrimazole and compound (I) were applied at doses of 3.25, 7.5, 15, 30, 60, 120, 240, and 480 g ai / ha, respectively. The test plants were then grown in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14-hour light; 65% humidity) and watered twice daily.

[0016] At 21 days post-application, visual damage to plants was assessed compared to untreated controls (0 = 0% damage; 100 = 100% damage). ED50 values ​​(estimated doses at which 50% damage was achieved) were obtained by linear regression analysis of the logit-transformed percentage of visual weed control against the logarithm of the application rate. RFs were then generated from the ratio of each ED50 to the ED50 of the susceptible population.

[0017] Table 1 Resistance Factors (RF) based on ED50 (LOLMU).

[0018]

[0019] Similar studies were conducted using various populations of *Alopecurus aequalis*, with each homogeneous population characterized as containing one of the mutations known to be associated with resistance to ACC enzyme herbicides (LL1781, CC2027). RFs were then generated from the ratio of each ED50 to the ED50 of the susceptible population, as previously described.

[0020] Table 2 Resistance Factors (RF) (ALOMY) based on ED50.

[0021]

[0022] Further studies were conducted using various populations of *Lycium chinense* that exhibited non-target site resistance (NTSR). Two separate populations were identified and sequenced in the UK to confirm the absence of ACC enzyme target site mutations and were characterized as having NTSR, as evidenced by their high resistance to the ACC enzyme inhibitory herbicide clodinafop-propargyl. Due to the extremely high level of resistance, the clodinafop-propargyl resistance factor could not be determined, but it was estimated to be >50.

[0023] Table 3 Resistance Factors (RF) based on ED50 (LOLMU - NTSR).

[0024] 。

Claims

1. A method for controlling the growth of monocotyledonous weeds resistant to ACC enzyme-inhibiting herbicides other than those having formula (I) in a site, the method comprising applying a herbicide composition comprising a compound having formula (I) to the site. 。 2. The method of claim 1, wherein the site further comprises monocotyledonous crop plants, and wherein the method selectively controls the growth of the monocotyledonous weeds resistant to ACC enzyme-inhibiting herbicides other than those having formula (I) in the site.

3. The method according to claim 2, wherein the crop is a cereal crop.

4. The method of claim 3, wherein the cereal crop is wheat or barley.

5. The method according to any one of the preceding claims, wherein the monocotyledonous weed is resistant to clodinafop-propargyl.

6. The method according to any one of the preceding claims, wherein the monocotyledonous weed contains one or more mutations in the ACC enzyme at amino acid positions selected from the group consisting of: I1781, W1999, W2027, I2041, D2078, C2088 and G2096.

7. The method of claim 6, wherein the monocotyledonous weed contains one or more mutations in the ACC enzyme at amino acid positions selected from the group consisting of: I1781, W2027, D2078, and C2088.

8. The method according to any one of the preceding claims, wherein the monocotyledonous weed is selected from the group consisting of: species of the genera *Alopecurus*, *Oat*, *Rhizophora*, *Gnaphalium*, and *Setaria*.

9. The method according to claim 8, wherein the monocotyledonous weed is selected from the group consisting of: large spike wild oat, wild oat, unfruitful wild oat, perennial ryegrass, multiflora ryegrass, Persian ryegrass, small clover, wild clover and foxtail grass.

10. The method of claim 9, wherein the monocotyledonous weed comprises ryegrass.

11. The method according to any one of the preceding claims, wherein the compound having formula (I) is applied to the site at a rate of 1 to 500 g / ha.

12. The method according to any one of the preceding claims, wherein the herbicide composition further comprises a herbicide safener.

13. The method according to any one of the preceding claims, wherein the herbicide composition comprises one or more additional herbicidal compounds.

14. The method of claim 13, wherein the one or more additional herbicides are selected from the group consisting of: sulfadiazine, mesosulfuron-methyl, and diflubenzuron.

15. Compounds having formula (I) Used for controlling monocotyledonous weeds resistant to ACC enzyme-inhibiting herbicides other than those having formula (I).

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