Sulfonylurea herbicidal activity

Extensive use of two more recendy developed classes of herbicides will further dramatically reduce the amount of appHed to control weeds. The sulfonylurea herbicides are extremely active compounds first discovered in the mid-1970s at DuPont they have been discussed extensively (78). Sulfonjiurea herbicides have experienced a rapid and widespread success since thek commercial introduction in 1982 with chlorsulfuron (Table 5). The sulfonylureas are appHed at rates of 2—75 g/ha. The chemistry of the sulfonylurea molecule permits the synthesis of a very large number of useful analogues, consequentiy many new herbicides are anticipated for crop production. As of this writing (1996), over 350 patents have been issued to about 27 agricultural companies covering tens of millions of stmctures known or expected to be herbicidaHy active. 

Agrochemical Products. The principal thiophene derivative in herbicidal protection, one of a range of sulfonylurea herbicides, is Harmony [79277-27-3] (Du Pont) (60), based on the intermediate methyl 3-aminothiophene-2-carboxylate (9). The product is characterized by a rapid biodegradabHity in the soil. Many other thiophene derivatives have been shown to have agrochemical activity, but few of these have been developed to the commercial level. 

Sales of agricultural products were 600 million in 1984. Du Pont expects to double this amount by 1990. There are many new products in the pipeline. Several of these new products are weed killers based on sulfonylurea chemistry. This family of weed killers is characterized by very low toxicity to mammals and high herbicidal activity at very low application rates in the field—often less than an ounce per acre of cropland. 

Figure 1. Three chemical families known to exhibit herbicidal activity through the inhibition of acetolactate synthase. A. sulfonylurea (sulfometuron) B. imidazolinone (imazapyr) and C. A representative triazolopyrimidine.

The selective toxicity of sulfonylureas to certain weeds without damage to the cereal crop arises from their rapid metabolism in the crop plant to inactive compounds, whereas in sensitive weeds the metabolism is much slower. The very high herbicidal activity suggests a specific biochemical mode of action, which is concluded to be the inhibition of plant cell division. Sulfonylureas block the enzyme acetolacetate synthase (ALS), which catalyses the biosynthesis of the essential branched chain amino acids valine, leucine and isoleucine. 

Inhibits ALS activity by 50%. A good correlation exists between the herbicidal activity of sulfonylureas and their ability to inhibit acetolactate synthase (2). This in vitro assay using the target enzyme along with the three-dimensioFTI structure of the enzyme should aid in the generation of a substantial data base that can be used to design potent inhibitors. 

Lolium biotypes exist which have resistance to the sulfonylurea herbicides chlorsulfuron and metsulfuron methyl (4). The biotype used in the studies presented here is resistant to both these sulfonylurea herbicides. Sulfonylurea herbicides inhibit the chloroplastic enzyme acetolactate synthase (ALS), also known as acetohydroxyacid synthase (AHAS) (16). Inhibition of this enzyme results in disruption of the synthesis of the branched-chain amino acids valine and isoleucine (161. The imidazolinone herbicides also inhibit ALS Q2). In some species auxins can protect against chlorsulfuron inhibition (S. Frear, USDA North Dakota, personal communication) the mechanistic basis for this protection is not known. We have measured the ALS activity in the resistant and susceptible Lolium and have also checked for any induction of ALS activity following treatment with the sulfonylurea herbicide chlorsulfuron. 

Site-directed mutagenesis was used to make additional amino acid substitutions at these sites in yeast ALS. At some of the sites, e.g. alall7, prol92, or trp586, nearly any substitution for the wild type amino acid that was tested resulted in a herbicide-resistant enzyme (Table I). Each of the mutant enzymes was characterized by enzyme assays to compare its activity, and its sensitivity to the sulfonylurea herbicide chlorimuron ethyl, to the wild type enzyme. These analyses have indicated that some of the mutations have little adverse effect on the activity of the enzyme, while decreasing sensitivity to the herbicide from three to greater than one thousandfold. The characteristics of these mutant enzymes were further evaluated in vivo in order to investigate the utility of particular herbicide/mutant enzyme combinations (Falco et al., manuscript in preparation). 

Many of the characteristics which combine to make ALS an excellent target for engineering beneficial herbicide resistance in crop plants may also lead to the proliferation of herbicide-resistant weeds. These characteristics include the following sulfonylurea herbicide resistance is a semi-dominant trait that is carried on a nuclear gene(s) ALS is the single primary site of action there are multiple positions in ALS that can be mutated to confer herbicide resistance mutant ALS enzymes can possess full catalytic activity. The latter property results in engineered crop plants that are fit, but can equally well result in weed biotypes that are fit. 

The ALS activity in each line is related to the activity in the absence of a sulfonylurea herbicide which is taken as 100 percent. 

The close correlation between seedling growth and AHAS activity resistance profiles is compatible with AHAS being the only site of action in corn for imidazolinone and sulfonylurea herbicides. A single mutation can offer either cross-resistance to both the imidazolinones and the sulfonylureas, or resistance only to the imidazolinones. 

Acetolactate synthase inhibition by imidazolinones and triazolopyrimidines, 460 sensitivity to sulfonylurea herbicides, 460 Acetolactate synthase gene activity and inheritance of resistance in tobacco, 461... 

Field dosages often span a very broad range, and the typical application rates , shown in Table 8.1, are for general comparison only. Nevertheless, these numbers indicate how field a.i. rates have decreased historically, as more active molecules have been developed examples include the neo-nicotinoid insecticides, triazole fungicides and sulfonylurea herbicides, which are one to two orders of magnitude more active than the early organochlorine, copper and aryloxyalkanoic acid pesticides, respectively. 

The systemic morpholine fungicide Corbel with fenpropimorph as its active substance is frequently applied to cereal cropping. It is rapidly metabolized in soil to fenpropimorphic acid. For the assay of fenpropimorphic acid in soil, GC-MS coupling109 has been proposed. The GC technique was used to assure the best separation for the fenpropimorphic acid from the complex soil matrix. The MS technique is very sensitive and assures the best reliability of the analytical information. The same reliability is also achieved when the HPLC-MS tandem system is used for sulfonylurea herbicide assay in soil.110... 

Sulfonylurea herbicides (SUHs) are relatively new herbicides, introduced in the 1980s. Chlorsulfuron was the first sulfonylurea marketed in the United States, in 1982. World-wide, 19 sulfonylureas had been commercialized by 1994, and five more are being developed. This rapid increase is due to their very high and specific herbicidal activity, which results in extremely low application rates of 10 to 40 g/ha. Furthermore, as compared to other herbicides, sulfonylureas are less toxic and degrade more rapidly. Chemical structures of some representative sulfonylureas are presented in Figure 25.2. From a chemical point of view, these herbicides are labile and weakly acidic compounds. The common names, chemical formulas, water solubility, pKa, half-life in soil, and leaching potential through the soil (when available) of the most representative sulfonylureas are reported in Table 25.2. 

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