2-氧代-2-苯基乙磺酰胺化合物组合合成与杀菌活性研究

为了快速获得具有高效杀菌活性的先导化合物,利用组合化学与传统合成方法相结合的方案,研究了N-取代-2-氧代-2-苯基乙磺酰胺类化合物对灰霉病菌的杀菌活性。首先以苯乙酮为原料,经过磺化、氯化反应,制备得到2-氧代-2-苯基乙磺酰氯,再分别与苯胺、苄胺和烷基胺组合库反应,制备了33个组合库,其中包含105个化合物,收率在60%~90%之间,纯度在70%~95%之间。筛选其中的10个活性库进行平行合成,得到29个化合物,又对其中10个活性化合物进行了纯化与结构鉴定。最后用灰霉病菌Botrytis cinerea对所有组合库与化合物进行离体与活体双重筛选,快速确定了高活性先导化合物,为进一步的结构优化奠定了基础。

Combined synthesis and fungicidal activity evaluation of the 2-oxo-2-phenyl ethyl sulfonamide derivatives

In order to rapidly prepare novel lead compounds of fungicides, the method that involved both the combinatorial chemistry and the conventional synthesis was used. The fungicidal activity against Botrytis cinerea of the N-substituted-2-oxo-2-phenyl ethyl sulfonamide derivatives were investigated. Firstly, 2-oxo-2-phenyl ethyl sulfonyl chloride was prepared by the sulfonation and chlorination of acetophenone. Then 33 combinatorial libraries, which contained 105 compounds, were synthesized by the reaction of 2-oxo-2-phenyl ethyl sulfonyl chloride respectly with aniline, benzylamine or alkyl amine combination library. The yields ranged from 60% to 90% and the purity was 70%-95%. Twenty-nine compounds were synthesized in parallel with 10 active libraries, within which 10 active compounds were purified and identified. In vitro and in vivo, all combination libraries and compounds were screened by Botrytis cinerea. Finally, the high activity lead compound was quickly determined, which lay the foundation for further structural optimization.