Design, synthesis and fungicidal activity of 11-alkoxyimino-5,6-dihydro-dibenzo[b,e] azepine-6-one derivatives

摘要

BACKGROUND: Macrocyclic compounds with an oxime ether side chain, discovered in Wang's group, showed good fungicidal activity. However, the long synthetic route makes the cost too high for them to be developed further as practical fungicides. Alternative compounds with good fungicidal activity and an easier synthesis than the above-mentioned macrolactams were sought, and a series of 11-alkoxyimino-5,6-dihydro-dibenzo[b,e]azepine-6-one derivatives (4) were designed and bioassayed. RESULTS: The structures were confirmed by ~1H NMR, ~(13)C NMR and LC-MS. The bioassay showed that about half of the 11-alkoxyimino-5,6-dihydro-dibenzo[b,e]azepine-6-one derivatives (4) displayed good fungicidal activity against Sclerotinia sclerotiorum (Lib.) de Bary, with EC_(50) values <15 μg ml~(-1), 11-(n-Butyloxyimino)-5,6-dihydro-dibenzo[b,e]azepine-6-one (4A-05), 11-(4-nitrobenzyloxyimino)-5,6-dihydro-dibenzo[b,e]azepine-6-one (4A-12) and 11-(2-chloro-6-fluorobenzyloxyimino)-5,6-dihydro-dibenzo[b,e]azepine-6-one (4A-21) displayed excellent fungicidal activity, with EC_(50) values of <2.5 μg mL~(-1), much better than the commercial fungicide chlorothalonil with an EC_(50) value of 7.16 μg mL~(-1). In addition, about half of the 11-alkoxyimino-5,6-dihydro-dibenzo[b,e]azepine-6-one derivatives (4) had good fungicidal activity against Botrytis cinerea (De Bary) Whetzel, with EC_(50) values of <10 μg mL~(-1).11-(2-Fluorobenzyloxyimino)-5,6-dihydro-dibenzo[b,e]azepine-6-one (4A-16), 11-(3-fluorobenzyloxyimino)-5,6-dihydro-dibenzo[b,e]azepine-6-one (4A-17) and 11-(2-chloro-6-fluorobenzyloxyimino)-5,6-dihydro-dibenzo[b,e]azepine-6-one (4A-21) displayed excellent fungicidal activity, with EC_(50) values of 3.73, 2.54 and 3.20 μg mL~(-1) respectively, comparable with the commercial fungicide procymidon with an EC_(50) value of 2.45 μg mL~(-1). Their structure-activity relationship is discussed. CONCLUSIONS: The present work demonstrates that the title compounds show promise as fungicides.