Triketone discovery

The triketones (Fig. 20), the most recent class of herbicides, were discovered in 1986 and introduced commercially (e.g. sulcotrione) in 1991. While several papers report that the triketones herbicides were derived from the plant secondary metabolite leptospermone (Fig. 20) that was isolated from the bottlebrush plant [Callistemon spp.) [Ref. 101], there is a report that suggests that the discovery may have been more serendipitous. ... 

Three tetracyclo[5.5.1.02,6.010,13]tridecanes are known at present. The reaction of glyoxal with dimethyl 3-ketoglutarate in aqueous solution at room temperature and pH 5 to give after treatment with acid c/,s-bicyclo[3.3.0]octane-3,7-dione has been discussed previously. More careful study of this condesation has led to the discovery that the two tetracyclic triketones 486 and 487 are also formed in low... 

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. 

A most surprising discovery came in the early seventies from the independent investigations at Hoffmann-La-Roche [51] and ScheringBerHn [52]. (S)-ProHne (3% mol equiv.) catalyzes the intramolecular aldolization of triketone 12 (Scheme... 

This chapter aims to give an insight into the discovery of the triketone class of herbicides and their continuing development. A very qualitative picture of structure-activity relationships will be discussed and currently commercialized triketones, in terms of their use, weed spectrum, crop selectivity, environmental and toxicological profiles, and manufacture will be described. This chapter also contains an overview of the major companies activities in the field in the last two decades, focusing on compounds that are likely to be brought to the market, or were putatively close to development. 

Independent of this discovery, in 1982 scientists from the same company were working on a project aimed at preparing novel Acetyl-CoA carboxylase inhibitors, based upon the typical cyclohexanedione structure known for this class. The first targeted compound (2), prepared as shown in Fig. 4.3.1, showed some herbicidal activity and they thus attempted preparation of a phenyl analogue in a similar manner. This led not to the expected product (3), but to the triketone (4). This compound was devoid of herbicidal activity, but (luckily ) in safener screens the compound showed antidotal effects in Soya for thiocarbamate herbicides. A further round of synthesis optimization was undertaken and it was found that the compound (5) with an ortho-chloro substituent showed reasonable herbicidal activity. Furthermore, they noticed that it exhibited the same unique bleaching symptomology observed for leptospermone (1, Fig. 4.3.1) [4]. Further optimiza-... 

Since their discovery in the early 1980s, the triketone herbicides have been extensively studied over the last two and half decades. In view of this, it may surprise the reader that only three commercial products have appeared to date. However, as has been described, other triketone products are due to appear on the market (e.g., tembotrione), and related compounds with this mode of action (see Chapter... 

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