Design,Synthesis And Herbicidal Activity Of Two Types Of Amide Derivatives

1.The control of resistant weeds is a challenge in the management of weeds.The development of novel herbicides with multiple action mechanisms is one of the potential approaches to control resistant weeds.In this study,guided by a multi-target drug design strategy,a series of isoxazolidamides were designed based on the structures of HPPD herbicide isoxaflutole（IFT）and N-isobutylbenzylamide mitosis inhibitor reported by Kumai Company.A total of 61 derivatives were synthesized,and their structure characterization and herbicidal activity were investigated.The herbicidal activity of the target compounds was evaluated by Petri dish test.SI-26and SII-23 showed 100%growth inhibition activity against Portulaca oleracea and Abutilon theophrasti under the dose of 10 mg·L^-1,and the action symptom is similar to that of N-isobutylbenzylamide mitosis inhibitor.The pre-and post-emergence herbicidal activities of the target compound were evaluated by pot experiment.SI-05 displayed excellent post-emergence herbicidal activity against Echinochloa crusgalli and A.theophrasti at 150 g a.i./ha,and induced bleaching effects similar to that of isoxaflutole.The exogenous addition test was carried out with Chlamydomonas reinhardtii.The results showed that the addition of homogentisate（HGA）could reverse the bleaching effect caused by SI-05,which indicated that the compound could inhibit the formation of HGA.The results of activity test in vitro enzyme showed the active entity of SI-05 inhibited HPPD enzyme activity with the IC₅₀ of 1.05μM,which proved that the compound was an inhibitor of HPPD enzyme.The interaction between the SI-05 active entity and HPPD enzyme was further studied by molecular docking method.The results showed that Fe²⁺in active site were chelated with two oxygen atoms of ligand,and the aromatic rings of benzylamine or aniline formed sandwich-shapedπ-πinteraction with Phe360 and Phe403 residues of the target enzyme.In addition,the cyanide bond of the compound SI-05 had an additional hydrogen bond interaction with Asn261.2.The enzymes involed in carotenoid biosynthesis pathway are an important type of herbicide targets.N-（3-fluorobenzyl）-3-methylbenzoamide discovered in our research group throughout a random screening procedure is a kind of novel carotenoid biosynthesis inhibitor.In this paper,lead optimization was carried out based on the structure of N-（3-fluorobenzyl）-3-methylbenzoamide.A total of 56 derivatives were designed and synthesized,and their herbicidal activity and SAR were investigated.The preliminary activity tests showed that compounds SIII-03 and SIII-21 led to a complete bleaching effect against E.crusgalli and P.oleracea at 3.13 mg·L^-1.The action of active title compound was faster than that of commercial herbicide diflufenican,and the leaves showed bleaching symptoms after 24 h of application.The results of structure-activity relationship showed that the group size and location of substituents on benzylamine benzene ring had significant effects on herbicidal activity.Introducing small substituents at meta-or para-position was beneficial to herbicidal activity,whereas the presence of groups at ortho-position resulted in the complete loss of herbicidal activity.Furthermore,introducing additional substituents at benzene ring of 3-methylbenzoyl decreased herbicidal activity of the derivatives.It should be noted that the change of amide side chain length significantly affected the mechanism of herbicide action.N-acylaniline derivatives inhibited the root and shoot growth of weeds,but did not cause bleaching symptom.