Herbicides discovery

Three approaches may be taken to discover new herbicides. They are (a) the random screening of chemicals, (b) the use of known herbicides as lead compounds for a synthesis program, and (c) the design of compounds interfering with known metabolic processes - the "rational" approach. There are no publications in the field of herbicide discovery that would suggest that the latter approach has advanced very much beyond the theoretical stage. The second approach, sometimes referred to as the "me-too" approach, has both positive and negative features. The... 

I would like to acknowledge the many contributions made by members of Dr. B. Cross and my Organic Synthesis Groups, the support and data provided by Drs. D. R. Ciarlante and P. L. Orwick and the Herbicide Discovery Group and the nmr analysis provided by Mr. F. Heim and Dr. P. C. Mowery of the Physical and Analytical Research Section. 

Copping G.L. Herbicides discovery. In Weed Management Handbook. BCPC. Blackwell Publishers, UK. 2002. 

Synthetic Herbicides. Most commercial phytotoxins (herbicides) have been discovered through random screening programs, followed by derivative synthesis and activity studies when a potential chemical candidate Is discovered. Seldom has a bloratlonal approach for herbicide discovery been achieved or used. Over the past 4S-50 years, perhaps close to a million compounds have been screened for herbicldal activity. The number of compounds screened has continually Increased and estimates for the 1980 s suggest that 12 to 15 thousand compounds per year were synthesized and screened for each compound reaching the market (28). In the 1990 s, the ratio may Increase 5-fo1d. 

Evaluation of natural compounds has been a relatively small part of the herbicide discovery effort of most companies involved in pesticide discovery. In some cases, the company has put significant effort into isolation of phytotoxic compounds from various organisms as part of a bioprospecting effort. This activity has led to several commercial herbicides, including glufosinate, bialaphos, the triketones, and pelargonic acid. 

The need exists to expand the repertoire of tools available for weed management systems. What little we know of the molecular target sites of natural phytotoxins indicates that they are inhibitors of a broad array of enzymes and other molecular targets that have not been the focus of herbicide discovery efforts [1]. At present, commercially available herbicides target a relatively limited number of enzymes and metabolic pathways. The discovery of new target sites is a growing emphasis of pesticide companies, especially since the U.S. Food Quality Protection Act has combined food tolerance levels of pesticides with the same molecular target sites. 

Our understanding of the biology and biochemistry of resistance allows the development of new concepts in herbicide discovery and development that reduce or eliminate resistance concerns. 

Figure 2 shows the early phase of research for flubendiamide. In 1989, Dr. T. Tsuda, at Osaka Prefecture University in Japan, reported that some pyrazinedicarbox-amide derivatives showed moderate herbicidal activity [5]. From 1990, the research for herbicide discovery was conducted at NNC Research Center. In the course of this research, a lead compound for an insecticide was discovered in 1993 from the class of benzenedicarboxamides as shown in Figure 2. This compound provided insecticidal activity on lepidoptera at the relatively high dose of 50-500 mg a.i./L. Moreover, it did not show activity against other species such as Hemiptera or Aca-rina. Although the level of activity was not satisfactory, this compound attracted the attention of researchers for both the novelty of its chemical structure and the characteristic insecticidal symptoms such as gradual contractions of the insect body. We therefore started the study for further optimization of this lead compound.

The authors would like to thank the members of the herbicide discovery effort at FMC for providing the initial lead and for the many helphil discussions from synthetic melhods to biological testing. 

Dayan, F. E., D. K. Owens, and S, 0, Duke, 2012. Rationale for a natural products approach to herbicide discovery. Pest Manage. Set, 68 519-528. 

RENDINA AND ABELL Biochemical Approaches to Herbicide Discovery 413... 

Hao GF, Zuo Y, Yang SG, Yang GF (2011) Protoporphyrinogen oxidase inhibitor an ideal target for herbicide discovery. Chimia 65 961-969... 

A ring-fused 2-pyridinone library was designed and syntiiesized for herbicide discovery. As a lead generation effort, tiiis library achieved its goal of producing actionable chemistry that warranted synthetic follow iq>. Substituents for tile library were chosen based on hrabicide lead-like properties and irqiut from product team scientists. The library produced molecules with herbicidal activity in broad leaf and grass weeds. 

The use of natural products as herbicides or as lead structures for herbicide discovery programs is another alternative. Spinosads are an example of outstanding success in this approach. However, natural products in general are more complex in stmcture and more difficult to synthesize. In most case, this approach is not cost-effective. 

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