The Progress towards Novel Herbicide Modes of Action and Targeted Herbicide Development

Abstract

To date, effectively controlling resistant weeds has been a great challenge in modern agricultural production. Developing new modes of action of herbicides would be an efficient, convenient, and timely means of controlling resistant weeds. In particular, new modes of herbicide action do not appear to have evolutionary resistance or cross-resistance with existing herbicides. However, a few successful herbicides with new modes of action (MoAs) have been marketed in the past 20 years. In this paper, we analyzed limiting factors for the slow development of novel herbicide MoAs. We then summarized the positive herbicide targets for the herbicides that have been discovered in recent years, such as Solanyl Diphosphate Synthase (SPS), Fatty Acid Thioesterase (FAT), Plastid Peptide Deformylase (PDEF), and Dihydroxy-Acid Dehydratase (DHAD). Some commercial herbicide varieties have been obtained based on novel herbicide targets, such as Homogentisate Solanesyltransferase (HST) and Dihydroorotate Dehydrogenase (DHODH). This provides a new reference and idea for herbicide molecular design in the future. In addition, some practical and efficient methods were mentioned for the rational design, discovery, and development of targeted herbicides development. In order to overcome the adverse conditions of compound druggability, prodrug strategies are also used in herbicide development, which can optimize the administration, permeability, absorption, and distribution of the original drug molecule or a candidate compound and may provide more possibilities for the development of new herbicides. The development of new herbicides is fascinating, the challenges and rewards are great, and the path to success is becoming more apparent.

Synthetic Approaches to the 2019–2020 New Agrochemicals

“…6 It efficiently controls important grass weeds in paddy field rice through inhibition of dihydroorotate dehydrogenase (DHOD), hereby blocking the de novo pyrimidine biosynthesis, which is a new mode of action for the herbicide market (Figure 4). 37,38 Template for SYNTHESIS Thieme…”

“…43 As nicofluprole is reported to act, just as cyproflanilide (30), as a selective antagonist of insect -aminobutyric acid (GABA) receptors, its pyrazole ring can be seen as cyclic isostere of one of the two meta-diamide functions (Figure 7). 53 The synthesis of nicofluprole (37) starts with the diazotization of the aniline 39 and the subsequent reaction of this diazonium ion with L-ascorbic acid. The obtained oxalhydrazide 40 is then transformed with tetramethoxypropane under basic conditions into the N-arylated pyrazole 41, which upon treatment with 1,3diiodo-5,5-dimethylhydantoin undergoes regioselective iodination to the 4-iodopyrazole derivative 42.…”

“…6 It efficiently controls important grass weeds in paddy field rice through inhibition of dihydroorotate dehydrogenase (DHOD), thereby blocking the de novo pyrimidine biosynthesis, which is a new mode of action for the herbicide market (Figure 4). 37,38 Figure 4 The herbicide tetflupyrolimet (18) The synthesis of tetflupyrolimet (18) starts with the alkylation of N-methylbenzylamine with 3-(trifluoromethyl)phenacylbromide (19). The ketone function of the resulting product 20 is then stereoselectively reduced to the (R)alcohol 21, which is converted into a mesylate leaving group and then treated with dimethyl malonate to afford the intermediate 22.…”

“…Nicofluprole (37) was announced by Bayer AG as a new insecticide in 2020. 6 It combines structural motifs of two insecticide classes: the fiproles, 51 such as fipronil (38), 52 and the meta-diamides, 44 such as broflanilide (31).…”

Design, Synthesis, and Biological Activity Determination of Novel Phenylpyrazole Protoporphyrinogen Oxidase Inhibitor Herbicides Containing Five-Membered Heterocycles

“…There are a wide variety and a large number of weeds worldwide, most of which pose a threat to agricultural production, leading to a significant reduction in food crop yields and becoming one of the important factors affecting agricultural production. , Although the first generation of herbicides promoted the process of agricultural production, the widespread use of herbicides, especially the repeated use of single herbicides or herbicides with the same mechanism of action, has led to a series of difficult to overcome problems, such as phytotoxicity, − pesticide residues, − the emergence of resistant weeds, − and the adverse impact on ecological environments such as water sources and soil, and even posed a threat to human health. − The emergence of a series of problems has posed more severe challenges to the development of chemical herbicides. Therefore, the development of new herbicides requires not only the advantages of target specificity, high efficiency, and strong targeting but also the characteristics of low toxicity, low pollution, low usage rate, and environmental friendliness. − …”