Synthesis and Fungicidal Activity of 2-Alkoxyimino-2-cyanoacetamide Derivatives

Abstract

A series of N-substituted 2-alkoxyimino-2-cyanoacetamide derivatives were synthesized and their fungicidal activities against cucumber downy mildew were assessed. Our studies of the structure-activity relationships revealed that fungicidal activity was the strongest when the substituents on the acetamide nitrogen were 4, 5-dihydroisoxazole groups. Among the compounds examined, 2-cyano-2-methoxyimino-N-(5, 5-dimethyl-4, 5-dihydroisoxazol-3-yl)acetamide (28) was more active than the original lead compound, cymoxanil.

Synthesis of biotin conjugates of the antifungal compound cymoxanil

“…The known acylisocyanate 7 appeared to be a suitable intermediate for the synthesis of 3 (Fig 2) and was prepared in two steps from the amide 5 following the literature procedure 13. Our initial plan was to react 7 with biotin derivative 2b to afford 3 directly.…”

“…Dimethyl sulfate (2.80 ml, 29.6 mmol) was added to a mixture of 2‐cyano‐2‐(hydroxyimino)acetamide ( 5 , prepared as in Reference 13; 3.00 g, 26.5 mmol), potassium carbonate (4.40 g, 31.8 mmol), and N,N ‐dimethylformamide (27 ml) at 5 °C, and the mixture was stirred at room temperature for 4 h. The mixture was then poured into water (175 ml) and extracted with ethyl acetate (2 × 175 ml). The organic layer was washed with brine (150 ml), dried over anhydrous magnesium sulfate, and concentrated to give an off‐white solid.…”

“…No syn/anti determinations were performed for compounds with an alkoxyimine moiety; however, 1 H and 13 C NMR spectra of the 3 and 4 indicate that they are single isomers and, by analogy with compounds prepared by similar methods (References 11–13), they are assumed to possess the E configuration.…”

“…In the design of bioconjugates, careful consideration must always be given to the site of attachment of the conjugated molecule, so that binding to the target protein is not disrupted. In the case of 1 this is particularly problematic since the structure–activity range is rather narrow10–13 and it was unclear where the biotin tag might be appended without preventing binding to the target site. Furthermore, a published study has suggested that an unidentified breakdown product of 1 is responsible for its antifungal activity;2 however, the structure of the active component has not been elucidated.…”

Synthesis and Fungicidal Activities of 2-(α-Methoxyiminobenzyl)-1-methylimidazole Derivatives

“…2,4) The fungicidal activity by preventive application was expressed as an index of 5, 4, 3, 2, 1 or 0, each corresponding to approximately 90% (cucumber powdery mildew) or 50%…”