Synthesis Of Hydroxyphenyl Substituted α-methylene-γ-butyrolactone Derivatives And Their Antifugal Activities Research

Hydroxyphenyl y-substituted α-methylene-y-butyrolactone compounds show well antifungal activity.Meanwhile,phenyl ethers and phenyl esters of natural pesticide as the most important product categories pharmacophore has great value for further development.Therefore,the present study is to keep the benzene ring on the α-methylene-γ-butyrolactone structure and the introduction of hydroxyl groups on the benzene ring,connectingα-methylene-γ-butyrolactone pharmacophore and benzene by hydroxyl esters,benzyl ethers pharmacophore synthesis derivatization,and screen out highly active compounds by activity assays,meanwhile,analysis compounds and structure-activity relationship.The main results of this dissertation are as followed.1 There are design and synthesis 55 kinds of ester compounds and 7 kinds of ether compounds.These compounds structure were confirmed by 1HNMR and 13CNMR and HR-MS(ESI).All kinds of ester and ether compounds are all new compounds by search the SciFinder database.2.The in vitro antifungal activities of the analogues against the fungal pathogen Botrytis Cinerea and Colletotrichum lagenarium by a spore germination assay.Results revealed that all synthesized analogues showed better inhibitory activities against B.Cinerea than the control compounds tulipalin A.Compound 55 exhibited highest antifungal activity with EC50 value of 4.56 mg/L in ester compounds respectively.Results also revealed that all synthesized analogues showed better inhibitory activities against C.lagenarium than the control compounds tulipalin A.Compound 60 exhibited highest antifungal activity with EC50 value of 15.63 mg/L in ethers compounds respectively.Compare the activity of these two bacteria,Colletotrichum lagenarium to be higher than the Botrytis Cinerea activity of esters;while ethers compounds opposite.QSAR analysis showed that benzene substituted acid ester of biologically active better than esterified fatty acids,and the activity of benzene substituents F,Cl and other halogen atoms higher than introducing CH3O,CH3 and other groups.Ethers compounds which synthesized with the longer alkyl chain activity are slightly higher than the short-chain.3.The in vivo activity against B.Cinerea of thirty analogues were tested and the efficiency value of compounds 7,8,20,24,38,46,55 were 47.35%,57.31%,52.04%,45.53%,52.54%,48.64%,55.89%at the concertration of 300mg/L,which were significantly higher than others and lowe rthan control agent procymidone(efficiency value=86.67%).The in vivo activity against C.lagenarium of twenty analogues were evaluated and compounds7,8,19,20,38 and 55were effective than chlorothalonil(efficiency value=71.67%)with efficiency value of 72.69%,73.67%,74.32%,75.54%,75.36%and 75.69%.Besides above compounds,the efficiency of compounds 45 and 46 were not significantly different with control agent procymidone.The above results show that:with the α-methylene retention-γ-butyrolactone this configuration,ester and ether compounds were synthesized via hydroxyphenyl,both showed a composition of antibacterial activity,hydroxyphenyl γ-substitutedα-methylene-γ-butyrolactone and α-methylene-γ-butyrolactone skeleton can be used for further synthesis.