Evolution of Strobilurins as Agricultural Fungicides

Several aspects of strobilurin fungicides, including the natural lead-structures, have already been summarized [2-9]. The elegant path that led to the discovery 

From the BASF group, a first review concentrated on the discovery of BAS 490 F (kresoxim-methyl), on pharmacophore variations and on structure-activity relationships at the mitochondrial target level [7]. Another paper was focused more on biokinetic features, and their affect on final biological properties [8j. In 1999 a general review summarized the historical evolution from natural products to commercial strobilurins up to trifloxystrobin, and the international R D competition, including some dramatic patent races [9j. Additionally, strobilurins have been reviewed in Russian, Chinese and Indian journals [10-13]. 

Another structurally related group of natural antifungal substances are the myxothiazols, which also contain an (E)-) -methoxyacrylate moiety, this time 7 -linked. Their discovery, characterization and structure elucidation was first performed in the German groups of H. Reichenbach and G. Hofle [21-23]. Later, the same groups discovered the closely related melithiazols [24]. For a review on the naturally occurring 7 -methoxyacrylates see Ref. [25]. 

Obviously, natural evolution led to fungi that synthesize and excrete substances that fight against competing fungi, while at the same time being completely insensitive to the fungicides they produce (see Section 13.2.6). 

An important Rosetta Stone came from the discovery that strobilurin A, oudemansin A and myxothiazol A not only share a common structural feature, namely 

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