Sulfonylurea discovery

Why have we put so much effort into the sulfonylureas Because we are convinced that available therapy can and will be improved. The problem of treating diabetes mellitus seemed once before to have been solved by the discovery and production of crystalline insulin in the early 1920 s. But the orally active sulfonylureas introduced 30 years later, though accepted initially with a great deal of caution and doubt, have now firmly entrenched themselves in the therapy of this disease. 

The use of microbes to discover targets of herbicide action is not limited to the sulfonylurea herbicides. Microbial experiments also have made Important contributions to the discovery of the sites of action of both glyphosate (45-48) and amlnotrlazole (49). With the development of sophisticated prokaryotic molecular genetics in numerous organisms that perform a variety of diverse functions, more and more processes will be dissected by microbial molecular biology. 

Levitt, G. Discovery of the Sulfonylurea Herbicides in Syndresis and Chemistry of Agrochemicals II,... 

Since the initial discovery of the first sulfonylurea herbicides by George Levitt at Du Pont in 1975, this compound class has attracted, and indeed continues to attract, very high interest and much activity within the agrochemical research domain. 

Since George Levitt s landmark discovery of herbicidal sulfonylurea herbicides at Du Pont in 1975 many hundreds of patents have been granted to Du Pont and, in addition, to over twenty other agrochemical companies. 

The discovery of the sulfonylurea herbicides, was certainly a dream fulfilled. As you will see, they provided ample opportunity to continue leaving footprints in the newly fallen snow. 

Figure 3 Sulfonylureas Tested Prior to Discovery of Plant Growth Activity...

The ultimate success of this discovery is demonstrated by the fact that there are fourteen commercialized and advanced candidate sulfonylurea herbicides. These compounds are useful in crops such as cereals, soybeans, rice, com, and canola as well as for noncrop use. TTieir low use rates favorable soil half-lives and low mammalian toxicity make them ideal products environmentally. These factors arc discussed in more detail by Brown and Kearney in the following chapter. 

The discovery of this site of action was quite consistent with the known very low animal toxicity of the sulfonylurea herbicides. Animals do not biosynthesize the branched-chain amino acids and do not possess the target enzyme acetolactate synthase. 

Conclusion. In this chapter, we have attempted a broad overview of the biochemical and environmental properties of the sulfonylurea herbicides. The history of these herbicides is distinguished by the apparently endless variation in structure leading to new weed control spectra, crop selectivities and soil degradation properties. They have already achieved significant use in j ctice, and it is likely that Dr. Levitt s discovery will continue to yield new herbicide tools offering viable solutions to the needs of world agriculture and of society. 

Levitt, G. "The Discovery of the Sulfonylurea Herbicides", this volume. Levitt, G. In Pesticide Chemistry Human Welfare and the Environment Miyamato, J. Kearney, P. C., Eds.Pergamon Press, New York, Vol. 1, 1983, 243. 

One of the many research programs which developed from George Levitt s discovery of herbicidal benzenesulfonylureas was the preparation and testing of bicyclic sulfonylureas 1. Their general structure contains a benzene ring, fused to a second ring in which the 3-position is attached via a carbon atom. X represents a heteroatom, or is a carbonyl group. 

As a result, a group of sulfonylurea compounds, which have (di)alkylaminocarbonyl group on the 3-position of pyridine ring, were found to be completely safe for com and hi ly active against most weeds. This discovery led to the invention of a potent sulfonylurea herbicide, SL-9S0 (3). (Scheme 1.)... 

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