Synthesis And Antifungal Activity Of Pyrimidine Derivatives Bearing Pyridine Ring Moiety

In recent years,the grain production was increased due to the extensive use of pesticides,while serious pollution was caused at the same time,which threatens the human health and resluts in the drug resistance.Nitrogen-containing heterocyclic compounds,due to their excellent biological activity,such as high efficiency,low toxicity have become important directions for the development of green pesticides.Among them,pyridine compounds and pyrimidine compounds are often used as two important heterocyclic compounds that also have strong systemic absorption,a unique mode of action and a broad spectrum of biological activity,such as fungicidal,insecticidal and herbicidal activities in agriculture.It gains widespread attention due to its function in anti-cancer,anti-inflammatory and anti-diabetics in medicine field.Two kinds of active groups were combined on the basis of rational molecular design and active sub-structure connection to design and synthesize two series of target compounds.The antifungal activity against two fungals containing B.cinerea and S.sclerotiorum was tested by mycelial growth rate method.The main research contents and results of this article are as follows:1.2-Mercapto-6-methylpyrimidin-4-ol was prepared by the reaction of ethyl acetoacetate and thiourea in the presence of KOH.the intermediate was reacted with pyridin-3-ylmethylchloride hydrochloride in an alkaline medium to yield 6-methyl-2-?pyridiny-3-methylthio?pyrimidin-4-ol.Then it was treated with POCl₃ to give 4-chloro-6-methyl-2-?pyridin-3-ylmethyl?thiopyrimidine,followed by reaction with substituted aniline in dioxane to afford the target compound N-?substituted phenyl?-6-methyl-2-??pyridin-3-ylmethyl?thio?pyrimidin-4-amine?I?.2.Ethyl 4-hydroxy-2-?methylthio?pyrimidine-5-carboxylate was prepared by the reaction of diethyl ethoxymethylenemalonate with S-methyl isothiourea sulfate in the presence of NaOH,followed by halogenation with POCl₃ to convert to its 4-chloro derivative.Subsequently,it was reacted with 3-picolyl amine to yield ethyl 2-methyl thio-4-??pyridin-3-ylmethyl?amino?pyrimidine-5-carboxylate,which was then hydrolyzed and acidified to give the substituted pyrimidine-5-carboxylic acid.Finally,it was reacted with different substituent amines or benzylamines to afford the target compound N-?substituented phenyl/benzyl?-4-??pyridin-3-ylmethyl?amino?pyrimidine-5-carboxamides?II?.3.The mycelial growth rate method was used to test the in vitro antibacterial activity of target compounds against B.cinerea and S.sclerotiorum.The experimental results showed that two series target compounds had certain antifungal activity against B.cinerea and S.sclerotiorum,and some were even better than the control agent.At the concentration of 50?g/mL,I_a had good antifungal activity against B.cinerea and S.sclerotiorum,the inhibitory rates of it were 79.88%and 62.35%respectively.At the concentration of 100?g/mL,I_a?I_d?I_g showed better antifungal activity,the inhibitory rates were 93.71%?89.66%and88.59%respectively,and antifungal activity was better than the control agent.The target compound of series II exhibited moderate inhibitory rate against B.cinerea and high inhibitory rate against S.sclerotiorum.At the concentration of 100?g/mL,the inhibitory rate of most compounds against S.sclerotiorum.was more than 90%,and the antifungal effect was better than that of the control agent.