Design, Synthesis, and Fungicidal Activity of Macrolactones and Macrolactams with a Sulfonamide Side Chain

• Published in: Journal of agricultural and food chemistry 2008-08, Vol.56 (15), p.6547-6553
• Main Authors: Zhu, Wei-Juan, Wu, Peng, Liang, Xiao-Mei, Dong, Yan-Hong, Zhang, Jian-Jun, Yuan, Hui-Zu, Qi, Shu-Hua, Meng, Xiang-Qing, Wu, Jin-Ping, Chen, Fu-Heng, Wang, Dao-Quan
• Format: Article
• Language: English
• Subjects: antifungal properties; Benzimidazoles - pharmacology; bioassays; Biological and medical sciences; Carbamates - pharmacology; chemical reactions; chemical structure; Crop and Animal Protection Chemistry; Drug Design; enzyme activity; Food industries; Fundamental and applied biological sciences. Psychology; fungicidal activity; fungicide; fungicides; Fungicides, Industrial - chemical synthesis; Fungicides, Industrial - pharmacology; Hydrogen Bonding; lactams; Lactams, Macrocyclic - chemical synthesis; Lactams, Macrocyclic - pharmacology; lactones; Lactones - chemical synthesis; Lactones - pharmacology; Macrocyclic Compounds - chemical synthesis; Macrocyclic Compounds - pharmacology; macrolactam; Macrolactone; pesticide; product development; Rhizoctonia - drug effects; Rhizoctonia solaniKühn; structure-activity relationships; sulfonamide; sulfonamides; synthesis; Thanatephorus cucumeris
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf800796z

Four series of novel macrolactones and macrolactams12-alkylsulfonamido-1,15-pentadecanlactones (5), 12-alkylsulfonamido-15-methyl-1,15-pentadecanlactones (6), 12-alkylsulfonamido-1,15-pentadecanlactams (7), and N-(alkylsulfonamidoethyl)-1,12-dodecanlactams (8)were designed and synthesized from readily available 2-nitrocyclododecanone or cyclododecanone. Their structures were confirmed by 1H NMR, IR, and elemental analysis. The bioassay showed that these compounds displayed fair to excellent fungicidal activity against Rhizoctonia solani Kühn and have a gradual increase of fungicidal activity in the order of 6, 7, 8, and 5. Among them, compounds 5a, 5b, and 5c displayed excellent fungicidal activity against R. solani comparable with the commercial fungicide carbendazim. Above results illustrated that the rule on the relationship between the activity and hydrogen-bonding, namely the macrocyclic compounds with a hydrogen-bonding acceptor and a hydrogen-bonding donor on the ring and having a three methylenes distance between two polarizable groups have the best fungicidal activity against R. solani, has a general suitability to the macrocyclic compounds, and pesticide molecules may combine with a target enzyme by hydrogen-bonding. The facts, which compound 6 has a much lower fungicidal activity against R. solani than compound 5 but their difference in chemical structure is only that there is a methyl group on the C15 for compound 6 and none but hydrogen atom on the C15 for compound 5, indicated that a methyl group plays an inhibitory role to the fungicidal activity. It suggests that the existence of a methyl group with a great volume between two polarizable groups would interfere in the interaction of pesticide molecules and the target enzyme.