Study On The Biological Activities Of Axially Chiral 1,3-thiazine Compound

There are many of chiral pesticides have been used with the racemic form that contains at least two enantiomers at the present market.However,only a fewer chiral pesticide was used in a single configuration.The chiral pesticides have been attracted considerable attention and become very signifigant to find the active agrochemical because of this type of pesticides have some advantages,such as high efficiency,less dosage and safer enviroment due to it posssess single configuration.To the best of my knowledge,the aixal chiral compounds have been fewer reported as the agrochemical compare to the commercial or under research chiral pesticides that usually have asymmetric carbon as chiral stereocenter.Thiazide unit are siginificant moiety and have been widely found in nature,medicine and agrochemical with various biological activities,such as antibacterial,antiviral,antitumor,immunomodulatory activities,plant growth regulator and insecticides.Therefore,we designed a series of axial chirality compounds containing1,3-thiazide skeleton,and synthesied this type molecules using different substituents thiourea as substrates by nitrogen heterocyclic carbene（NHC）catalyzed.We also tested the obtained compound for toxicity against plant virius and insecticides.1.For Antibacterial:The total 39 target compounds were synthesized with three configurations（R,S,rac）.Four bacteria（blight of rice（Xoo）,citrus canker（Xac）and tobacco bacterial wilt.Virus（Rs）and kiwifruit bacterial canker（Psa））were tested for activity with turbidity method.The results showed that most of the synthesized ones had moderate to good inhibitory activity against B.oryzae（Xoo）,four compounds showed moderate inhibitory activity against Citrus canker（Xac）,and some others show only moderate inhibitory activity against R.solanacearum（Rs）and kiwifruit bacterial canker（Psa）.Among them,5f（S）showed good in vitro inhibitory activity against B.oryzae,the inhibition rate was as high as 92.16%at a concentration of 100μg/m L(EC₅₀=4.18),which was lower than that of the control drug thiophanate(EC₅₀=37.35),and metazole（EC50=16.22）.2.For Insecticidal:The synthesized target compounds were tested for activity against diamondback moth by leaf dipping method,among which 5d（rac）,5j（R）,5k（R）had high inhibitory activity at the concentration of 500μg/m L at 80%.3.Rice in vivo pot experiment:We selected 5c（S）and 5f（S）for the rice in vivo pot experiment test.The test results show that 5c（S）and 5f（S）have the ability to inhibit bacterial blight in rice.Better protection effect,its control effect was 39.00%,53.70%respectively,of which 5f（S）was better than the commercial agent equatazole（47.26%）and thiophanate copper（20.02%）.The target compounds 5c（S）and 5f（S）have a certain therapeutic effect on rice bacterial blight,and their control effects are 48.10%and 45.90%,respectively,which are better than the commercial agent thiophanate copper（37.22%）.4.Mechanism test:We used label-free quantitative proteomic analysis to further explore the mechanism of action of the highly active compound 5f（S）on rice and B.oryzae.The results of the mechanism of action of B.oryzae showed that the number of differential proteins in B.oryzae treated at a concentration of 100μg/m L was 125,including 69 up-regulated proteins and 36down-regulated proteins.Analysis of the experimental results,we speculate that compound 5f（S）affects the metabolic activity of the pathogen by regulating the metabolic process of nicotinate and nicotinamide,thereby inhibiting the growth of the pathogen.The experimental results of the mechanism of action on rice showed that when the rice was treated with the rice pot method at a concentration of 200μg/m L,there were 366 differential proteins,including 97 up-regulated proteins and 269 down-regulated proteins.The effects of 5f（S）are mainly concentrated in the metabolic process,cellular process,catalytic activation process and antioxidant process,etc.It has a significant impact.Through the analysis of KEGG pathway data,compound 5f（S）stimulates the immune system of rice,thereby inhibiting the proliferation and infection of pathogens..