Design,Synthesis And Bioactivity Studies Of Novel Pyrimidyl AHAS Inhibitors

Acetohydroxyacid synthase(Acetohydroxyacid,synthase,AHAS)is the key enzyme for the first step in catalyzing the biosynthesis of branched chain amino acid,so the commercialized inhibitors targeting this enzyme are widely used for its characters of high efficiency and low toxicity,broad spectrum of grass killing and high security.However,due to long-term and irrational abuse,the problem of resistance to herbicides of the enzyme is becoming more and more serious.The main reason for the resistance is the rite-directed mutagenesis of the AHAS conservative amino acid residues,in which the resistance caused by mutation of P197L and W574L is the most serious problem.Based on the analysis of the P197L,one of the most serious causes of resistance,combined the mechanism of action of AHAS with small molecule inhibitors,we designed and synthetize two types of novel AHAS inhibitors on the basis of prophase work of the commercialized inhibitor BS ethers,which caused the weakest resistance,and then tested its biological activity.The specific research work are as follows:1.Introduced the structure and function of AHAS and described the progress and development of AHAS inhibitors.2.Designed and synthesized two series of 57 new AHAS inhibitors,including 25 compounds containing indole ring fragment and 32 compounds containing pyrazole ring fragment.All target compounds were characterized by 1H NMR,13C NMR and HRMS analysis.3.The enzyme activity in vitro of synthesized target compounds and the activity of herbicidal in living bodies were respectively tested.The experimental results showed that a few compounds put up great inhibitory activity to Brassica juncea,Chenopodium serotinum at a concentration of 150 g ai/ha.The inhibitory activity of Compound Ⅱ-13(Y17429)in 150 g ai/ha to Brassica juncea,Chenopodium serotinum can respectively reach 80%,100%,80%,Among them,compounds Ⅱ-13(Y17429)and Ⅱ-24(Y17440)displayed the value for potential investigated and further optimization.This paper preliminarily summarizes the structure-activity relationship of the two kinds of inhibitors,and provides a meaningful reference for the subsequent design of a new type of AHAS inhibitor.