Design,Synthesis And Biological Activity Of The Novel Triketone Class Of HPPD Inhibitors

In the 1990s,p-Hydroxyphenylpyruvatedioxygenase(HPPD)was first identified as the herbicide target with a novel mode of action.HPPD is an important enzyme in the catabolism of tyrosine,which can catalyze the conversion of p-hydroxyphenyl pyruvic acid(HPPA)into homogentisic acid(HGA),and HGA is an important precursor for biosynthesis of plastoquinone and tocopherols.Once HPPD inhibited,the photosynthesis of plant will be blocked,making the plant appear albino symptoms and ultimately death.Herbicides targeting HPPD had various advantages such as high efficiency,low toxicity,high crop safety,broad-spectrum weed control(including some resistant weeds),good environmental compatibility,and safety to after-reap crops.In order to search for novel and more potent HPPD inhibitors,in this thesis,we have systematically summarized about HPPD and its inhibitors(based on the latest research progress),and the design and synthesis of a series of novel triketone-aryloxyphenyl hybrids Ⅱ(41 compounds)triketone-quionline hybrids Ⅲ(11 compounds).All the target compounds were systematically characterized through 1H NMR,13C NMR and HRMS.The syntheized compounds were evaluated for their in vitro AtHPPD inhibitory activity and green house herbicidal activity,and further established their structure-acvity relationships.The results of in vitro experiments showed that most of the target compounds displayed strong inhibitory activity against AtHPPD.In particular,the enzyme inhibitory activities of compounds II-7-a7(IC50=0.031± 0.004μM)and II-7-b14(IC50=0.031±0.006 μM)were nearly 10 times when compared to commercial herbicide Mesotrione(IC50=0.342±0.010μM).The green house herbicidal activity results indicated that some of the compounds showed good to excellent post emergence herbicidal activity at the application rate of 150 g ai/ha.In particular,four compounds II-7-b15,II-7-b17,Ⅱ-7-b18、Ⅱ-7-all.Ⅲ-12-a2 and Ⅲ-12-a3 were exhibited higher activity(>80%inhibition rate)against broadleaf weeds such as Mustard,Peony,and Sorrel weeds.