title: Design, synthesis and fungicidal activity of 11-alkoxyimino-5,6-dihydro-dibenzo[b,e] azepine-6-one derivatives.
abstract: 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 (1) H 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 EC50 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 EC50 values of <2.5 µg mL(-1) , much better than the commercial fungicide chlorothalonil with an EC50 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 EC50 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 EC50 values of 3.73, 2.54 and 3.20 µg mL(-1) respectively, comparable with the commercial fungicide procymidon with an EC50 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.
authors.affiliation: Key Laboratory of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, Beijing, PR China.
authors.forename: Yan-shuang
authors.initials: YS
authors.lastname: Xiao
authors.forename: Xiao-jing
authors.initials: XJ
authors.lastname: Yan
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Xu
authors.forename: Jia-xing
authors.initials: JX
authors.lastname: Huang
authors.forename: Hui-zhu
authors.initials: HZ
authors.lastname: Yuan
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Liang
authors.forename: Jian-jun
authors.initials: JJ
authors.lastname: Zhang
authors.forename: Dao-quan
authors.initials: DQ
authors.lastname: Wang
mesh_terms: D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D005658:Fungi / Q000187:drug effects; D005659:Fungicides, Industrial / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D005659:Fungicides, Industrial