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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。
In order to rapidly obtain lead compounds with high bactericidal activity, the bactericidal activity of N-substituted-2-oxo-2-phenylethanesulfonamides against Botrytis cinerea was studied by a combination of combinatorial chemistry and traditional methods . First acetophenone as raw material, after sulfonation, chlorination, prepared 2-oxo-2-phenyl ethanesulfonyl chloride, and then with aniline, benzylamine and alkylamine combination library reaction prepared 33 The combined library contains 105 compounds with yield of 60% -90% and purity of 70% -95%. Ten active libraries were screened for parallel synthesis, 29 compounds were obtained, and 10 of them were purified and structurally identified. Finally, all the combinatorial libraries and compounds were screened in vitro and in vivo with the Botrytis cinerea. The rapid determination of highly active lead compounds laid the foundation for further structural optimization.