Essential herbicidal activity

This paper traces in some detail the path which led to the discovery of a new class of herbicides, the 2-(5-oxo-2-imidazolin-2-yl)arylcarboxylates. The journey started when it was found that a phthalimide, a-isopropyl-a-methyl-l,3-dioxo-2-isoindoline-acetamide, had sufficient herbicidal activity to warrant further synthesis effort. This work led to a series of analogs essentially devoid of herbicidal activity yet possessing interesting plant growth regulating effects. Further chemical modifications resulted in the synthesis of two new groups of compounds, imidazoisoindolediones and dihydro-imidazoisoindolediones, and the return of herbicidal activity. The imidazoisoindolediones were in turn transformed into o-(5-oxo-imidazo-lin-2-yl)benzoates, the first members of a very interesting new class of herbicides. 

The discovery of the imidazolinotte herbicides had its beginnings in a random screening test some 12 years ago. The phthalimide 1 prepared originally as an anticonvulsant at Cyanamid s Lederle Laboratories had sufficient herbicidal activity to warrant the synthesis of additional members of this series. One of these, the chloro analog was essentially devoid of herbicidal activity but had instead a pronounced... 

Bipyridyliums with redox potentials in the range of -300 to -500 mV, such as diquat and paraquat, can accept electrons in competition with the acceptor of photosystem I (Figure 2, site 4) and have herbicidal activity. Interception of electron flow from photosystem I essentially shunts the electron transport chain. 

Therefore, it is difficult to define a reasonable basis for selecting any of the parent series previously examined by Fujita et al. (11) as a model for the TFMS series of the present study. Indeed, some initial Hansch analyses of our TFMS pre-emergence herbicidal activity data using Fujita s phenoxyacetic acid substituent n values produced very poor correlations. We thus deemed it prudent (if not essential) to determine experimentally w values for all substituents in the TFMS series. 

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. 

Another question that needed to be raised was whether the configuration at the C-3 carbon position where the benzyloxy group is attached to plays an important role in activity. The 3-epimer was synthesized and tested in our screens and was found to be essentially devoid of herbicidal activity. This result clearly demonstrated that a cis relationship between the ethyl group and the benzyloxy group is required for activity. 

Some essential oils are not only insecticidal but also possess strong phytotoxic effects. In many cases, this would be considered a serious drawback to the use of these essential oils for insect pest control however, this also opens the door to the use of some oils as herbicides. Although few studies have addressed this herbicidal activity, work completed by Tworkoski [25] demonstrated that the... 

The herbicidal activities varied with substituents Ri, R2 and R (Table 2.5.4). The a-hydrogen atom is, probably, essential for the herbicidal activity because the di-... 

Certain 1,3,4-thiadiazoles, particularly 2-ureido-derivatives, possess herbicidal activity. - l-Methyl-3-(5-t-butyl-l,3,4-thiadiazol-2-yl)urea controls a broad range of weeds when sprayed on the foliage of the seedlings or the surface of the soil at a dosage of 1—2 kg/hm . The 1,3,4-thiadiazole nucleus appears to play an essential part in the activity, since analogous thiazoles are ineffective. The urea derivatives (184) and (185) (previous... 

Verdeguer, M., D. Garcia-Rellan, H. Boira, E. Perez, S. Gandolfo, and M. A. Blazquez, 2011. Herbicidal activity of Peumus boldus and Drimys winterii essential oils from Chile. 16 403-411. 

Some of these phenylacetic esters exhibit excellent wheat selectivity and compound 1 (Ri=H, R2=CH3) was field tested for this utility several years ago. However, both a-substitution (Ri=CH3) and higher alkyl esters (R >C3) resulted in diminished overall levels of herbicidal efficacy. Furthermore, both the cinnamate esters of formula 2 and their dihydro analogs 3 were essentially devoid of herbicidal activity at commercially feasible application rates. 

Only the D-isomer of these compounds shows strong herbicidal activity, while the L-isomer is inactive, and any additional substituents on the benzene ring significantly decrease the activity (6). Thus we speculated that the phenoxypropanoic acid part of the structure is the essential moiety, which interacts with a receptor in plant tissues. And if this is so, the pyridinyloxy moiety may serve to optimize the hydrophobicity of the whole molecule for maximum herbicidal activity, enhancing the translocation of the molecule through the plant. 

The activity of anionic surfactants is intimately related to the configuration of their alkyl chains [267]. At concentrations at which surfactants differently affected herbicide activity, differences in surface activities and conductivities could be detected, but could not be correlated with the biological action Jansen concludes that surface activity does not affect the biological activity per se, but rather it is the solution properties of the surfactants which are influential. Solubility of the herbicides in surfactant solutions was found to be a useful guide to activity, but was not sufficiently related directly to it to make this one characteristic a foolproof pointer [268]. It is essential that precise physical data are obtained on herbicide-surfactant-water systems and that their ability to interact with lipoidal membranes is determined. 

The results of SAR analysis for IG were similar to those for IC-IF, i.e., substituents Yn on the phenoxy-benzene ring greatly affected the herbicidal activity, and 2- and 4-positions in the phenoxy-benzene ring were the most essential. It showed that the fur-2-yl group was beneficial to herbicidal activity when the compound had Y as 2,4-Cl2 in structure IG. 

Sodium l,l-dimethoxyethyl(methyl)phosphinate 2 was found to be the most effective herbicidal compound among plant PDHc El inhibitors by Baillie et al. s work. 2 was presumably hydrolyzed to sodium salt of acetyl(methyl)phosphinic acid 1-2 in vivo to exhibit herbicidal activity (Scheme 4.10). 1-2 displayed higher enzyme inhibition and herbicidal activity than 1-1. It has been found that 1-1 was a competitive inhibitor of PDHc, but 1-2 caused time-dependent inhibition. Baillie et al. gave a possible explanation for this result, the initial binding of inhibitors to the pyruvate site and subsequent reaction with thiamine pyrophosphate were rapid and reversible for both 1-1 and 1-2. In the case of 1-2, an enzyme-inhibitor complex was first formed and then underwent a time-dependent, essentially irreversible transformation to produce a more tightly bound form. In other words, 1-2 could act as a slow, tight binding inhibitor [1]. 

The Baillie et al. s study on plant PDHc El inhibitor showed the structure of acetylphosphonates made an essential contribution to the inhibition against plant PDHc El. It is interesting to compare the effect of substituents on enzyme inhibition and herbicidal activity in acetylphosphonates and alkylphosphonates lo. 

SAR analyses indicated that R R, and Y in the alkylphosphonates lo were the most essential sites for both enzyme inhibition and herbicidal activity. Me or Na as R and R, and 2,4-Cl2 as were most beneficial to activity. When 2,4-Cl2 were kept constant as Y , enzyme inhibition could be greatly enhanced by the chemical modification of R and R. Sodium salts IIB-2 and IID-10 exhibited more powerful enzyme inhibition than the corresponding alkyl phosphonates IC-22 and IG-21. However, good enzyme inhibition and herbicidal activity required an optimal combination of R, R, R, R", and Y in... 

Biorational approaches have proven useful in the development of classes of herbicides which inhibit essential metaboHc pathways common to all plants and thus are specific to plants and have low toxicity to mammalian species. Biorational herbicide development remains a high risk endeavor since promising high activities observed in the laboratory may be nullified by factors such as limitations in plant uptake and translocation, and the instabiHty or inactivity of biochemical en2yme inhibitors under the harsher environmental conditions in the field. Despite these recogni2ed drawbacks, biorational design of herbicides has shown sufficient potential to make the study of herbicide modes of action an important and growing research area. 

Thus, a synthetic source of promising allelochemicals is essential if we are to comprehensively study the agent s mode of activity and establish its basic structure-activity profile. The proposed work addresses this need. We will synthesize alleopathic natural products isolated from the sunflower (the heliannuols), and structurally related compounds, in optically pure form based on biomimetic phenol-epoxide cyclizations. The bioactivity of the targets and intermediates will be evaluated through laboratory tests on plant germination and growth. Bioassays will be performed on the synthetic intermediates to allow for the development of a preliminary structure-activity profile for these novel natural herbicides. 

In recent years, agribusiness firms have developed pf empirically several compounds that inhibit essential steps in the biosynthesis of amino acids found in plants but missing in animals. One of these compounds, glyphosate, is a highly specific inhibitor of 5-enol pyruvyl-shikimate-3-phosphate synthase (an enzyme needed for aromatic amino acid biosynthesis). Glyphosate is the active ingredient in the widely used herbicide Roundup. 

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