Design, synthesis, and fungicidal activity of macrolactones and macrolactams with a sulfonamide side chain.
Four series of novel macrolactones and macrolactams12-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 (1)H NMR, IR, and elemental analysis. The bioassay showed that these compounds displayed fair to excellent fungicidal activity against Rhizoctonia solani Kuhn 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.
Zhu
Wei-Juan
WJ
Key Laboratory of Pesticide Chemistry and Application Technology, Department of Applied Chemistry, China Agricultural University, and Institute of Plant Protection, Chinese Academy of Agricultural Science Beijing, People's Republic of China.
Wu
Peng
P
Liang
Xiao-Mei
XM
Dong
Yan-Hong
YH
Zhang
Jian-Jun
JJ
Yuan
Hui-Zu
HZ
Qi
Shu-Hua
SH
Meng
Xiang-Qing
XQ
Wu
Jin-Ping
JP
Chen
Fu-Heng
FH
Wang
Dao-Quan
DQ
D001562:Benzimidazoles / Q000494:pharmacology; D002219:Carbamates / Q000494:pharmacology; D015195:Drug Design; D005659:Fungicides, Industrial / Q000138:chemical synthesis* / Q000494:pharmacology; D006860:Hydrogen Bonding; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D012232:Rhizoctonia / Q000187:drug effects
D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; D047029:Lactams, Macrocyclic; D007783:Lactones; D047028:Macrocyclic Compounds; C006698:carbendazim