Synthesis And Fungicidal Activity Of 2-Acylaminocycloalkylsulfonamides

As very important sulfur-containing analogs of amino carboxylic acids, β-aminoethanesulfonic acid derivatives have been widely used in areas such as medicine, natural products. While so far its derivatives are rarely reported. In order to discover highly active compound with novel structure, mainly taken Chesulfamide (Ⅲ-1) as the lead compound, by structure optimization, compound library of β-acylaminocycloalkylsulfonamides was constructed. Firstly, twelve 2-ocycloalkylsulfonamides (Ⅲ) were synthesized, and then by reductive amination, twelve novel 2-aminocycloalkylsulfonamides (Ⅳ) were obtained. Based on these synthesis work, compound 2-aminocyclohexylsulfonamide (Ⅳ-1) was chosen as the important intermediate, after reacted with numerous acyl chloride, forty-two novel 2-acylaminocycloalkylsulfonamides (V-1～V-42) were synthesized, and the most active acyl chloride group was screend out as trichloroacyl chloride in the later activity screening. So, it was considered as the active group, by active group splice with the other eleven 2-aminocyclohexylsulfonamides, eleven novel 2-acylaminocycloalkylsulfonamides (V-43～ V-53) were obtained. Finally, structure of the above fifty-three title compounds confirmed by 1H NMR, MS, IR and X-ray diffraction.In terms of bioassay, firstly against fourteen Botrytis cinerea strains collected from different areas of Liaoning province, fungicidal activity of the title compounds was tested; then three rounds screening in vitro was performed by mycelium growth rate method, fungicial spectrum and screening in vivo were conducted at last.Structure-activity relationship between acylamino, cycloalkyl group and fungicidal activity was studied meanwhile. Primary structure-activity relationship showed that activity was high if acyl chloride was substituent benzoyl chloride as well as one group of 2-methyl, 2,5-dimethyl,4-methoxyl,3-chloro,2,5-dichloro,2-trifiuoromethyl and 3-trifluoromethyl was on the benzene ring. Similarly, it was high when alkylacyl chloride was w-hexanoyl chloride or n-heptanoyl chloride. Halogenated chloride was generally higher,2-halogeno was higher than 3-halogeno, chloro was higher than bromo. In the meantime,2-alkoxyl and 2-alkylthiol acetyl chloride also showed high activity. From view of relationship between compounds V-30, V-31, V-32 and their ECso, it was indicated that fungicidal activity was gradually increased as the number of chloride atom increasing. Of which, performance of compound V-32 was outstanding, its EC50 against five Botrytis cinerea was from 0.41 mg/L～3.64 mg/L which was higher than both of the contrast agent Procymidone and the lead compound Chesulfamide. In the end, during the forty-two kinds of acyl chlorides, it was to be sure that trichloroacetyl chloride had the greatest contribution to activity, therefore, it was marked as the active in the later structure-activity relationship research of cycloalkyl group.As to the structure-activity relationship between cycloalkyl group and fungicidal activity, compounds with five, six, seven and eight membered cycloalkyl exhibited generally higher activity, especially the six membered was excellent, its EC50 was from 0.15 mg/L to 3.64 mg/L. Moreover, for compound from V-47 to V-53, it was concluded that when substituted alkyl group on cyclic ring increasing, activity was reduced. The location of alkyl group on the ring also made a big difference, for example, in order, activity was 4-methyl,5-methyl, 3-methyl.All above indicated that V-32 and V-43 was excellently active. In addition, six compounds showed high fungicidal activity after validation by pot test. Fungicidal activity of compound 2-trichloroacylaminocloalkylsulfonamide was excellent, apparently higher than the contrast agent Procymidone and the lead compound Chesulfamide. It was concluded that 2-acylaminocycloalkylsufonamides showed potential fungicidal activity.