Synthesis And Fungicidal Activity Of 2-Acyloxycycloalkylsulfonamides

On the former work, we had been working with the research of 2-Oxo droxycycloalkylsulfonamides. And they had better activity against Botrytis cinerea Pers. On the basis of this, Eleven novel 2-oxocycloalkylsulfonamides (3) and twenty-one novel 2-hydroxycycloalkylsulfonamides (4) derivatives were synthesized, and their structures were confirmed by1H NMR, IR, and Elemental analysis.The bioassay showed that the compounds 3 and 4 have excellent fungicidal activity against B. cinerea both in vitro and in vivo. From the aspect of structure-activity, the compounds containging a 7-membered ring (3C and 4C) and 8-membered ring (3D and 4D) make the most contribution than those containing a 5,6 or 12-membered ring of the fungicide activity, with reduction and increase of the rings' sizes, the activity is significantly decreased. Using the mycelium growth rate test, the best antifungal activity can be seen from compounds 3C,4C,3D and 4D, the EC50 value of which are 0.80,0.85,1.22 and 1.09 mg/L, respectively. The results of the spore germination test indicated that most of the compounds exhibited obvious inhibitory effects against B.cinerea. Compounds containing a small ring showed better activity than those containing a large ring. Furthermore, the inhibition rate of the 2-oxocycloalkylsulfonamides are higher than the 2-hydroxycycloalkylsulfonamides, among them, compounds 3A,3B17,3E,4A, with EC50 value of 4.21,4.21,3.24, and 5.29 mg/L, respectively. The results of the pot culture test showed that almost all compounds have a better control effects in vivo, and the 2-hydroxycycloalkylsulfonamides were obviously superior to the 2-oxocycloalkylsulfonamides, among them compounds 3E,4B17 and 4C have higher control efficacy than procymidone on cucumber plants.The bioassay showed that the compounds 2-hydroxycycloalkylsulfonamides have excellent fungicidal activity against B.cinerea Pers in vitro and in vivo. In our present work, the 2-position hydroxyl was converted to the corresponding acyloxy. Many new derivatives were designed and synthesized for the purpose of novel and effective pesticide discovery. The fungicidal activities of those new compounds against ten fungus were evaluated using the mycelium growth rate tests. The fungicidal activities of the compounds against B.cinerea were evaluated using the mycelium growth rate tests and pot culture tests.The synthetic route of compounds (6) is shown in Scheme 2. Twenty-six novel 2-acyloxycycloalkylsulfonamides derivatives were synthesized, and their structures were confirmed by 1H NMR, IR, and Elemental analysis.The results of the fungicidal spectrum test showed that all 2-acyloxycycloalkyl-sulfonamides exhibited a different extent of fungicidal activity at the concentration 50 mg/L. Among them the compounds 5B12,5B13,5B25 and 5B26 have better fungicidal activity and the inhibition ratio nearly reached 70%.According to the results of the mycelium growth rate test against B.cinerea, the EC50 and ECgo values of the compounds 5B8,5B12,5B13,5B18,5B21,5B22,5B25 and 5B26 were similar to or better than commercial fungicide procymidone. For example the EC50 and EC80 values of the compounds 5B25 were 4.17 and 11.35 mg/L, respectively, and were better than commercial fungicide procymidone which were 4.46 and 35.02 mg/L. The results of the pot culture test showed that the inhibition ratio of compounds 5B13,5B25,5B26 in vivo at the concentration 200 mg/L were better than commercial fungicide procymidone.Combinatorial chemistry is one of the important new methodologies developed by academics and researchers in the pharmaceutical, agrochemical, and biotechnology industries to reduce the time and costs associated with producing effective, marketable, and competitive new drugs.We devise 16 non-uniform libraries of the 2-acyloxycycloalkylsulfonamides by the principle of combinatorial synthesis, and their structures were monitored by GC-MS. The libraries will then be screened for fungicidal activity against B.cinerea Pers in vitro and in vivo and those compounds that show good activity will be identified and characterized.The results of the mycelium growth rate test against B.cinerea showed that all 2-acyloxycycloalkylsulfonamides from the 16 pots exhibited a different extent of fungicidal activity against B.cinerea. Among them, Pot I-5,I-7 and I-8 showed better fungicidal activity than commercial fungicide pyrimethanil. The results of the pot culture test showed that most of the 16 pots showed some fungicidal activities in vivo against the B. cinerea. Among them, Pots I-7 and I-8 showed the best fungicidal activities. The control efficiency of the compounds in libraryⅠis significantly better than the compounds in libraryⅡin vivo. From the results of the preliminary screening, it was decided that pots that exhibited better fungicidal activities both in vitro and in vivo would warrant further evaluation of their components individually. Thus, the 1-7 and 1-8 were synthesized and characterized separately, this is similar with the traditional synthesis but obviously improve the screening efficiency of the compounds.