Synthesis And Antibacterial Activity Of Caraway Acid Derivatives Of A. Chinensis

Objective:Lophanic acid is one of the effective components of the fungal resistance of oh ga liang(Isodon flavida),which belongs to the abietane diterpenes.In the early stage of the investigation of Miao medicine,our group learned that the leaves of oh ga liang(I.flavida),a common herb of the Miao people in the area of Lei Gong Mountain in Qiandongnan,Guizhou Province,were used to treat beriberi,and the effect was better.The original plant,active components and antifungal activity were followed up,and the active components were found and isolated into lophanic acid.In order to find out and master the active sites in the molecular structure of the active component threaded lophanic acid,we should further explore the high efficiency,low toxicity and safe antibacterial activity new drugs or lead compounds,In this paper,we used the lophanic acid as the starting material for derivatization and evaluated the antibacterial activity of the synthesized compounds.Method:The main research contents and methods are as follows:1.design the synthesis route of the derivatives by analyzing the three-dimensional structure of the C-20 carboxyl groups,acylation of the C-13 hydroxyl groups,electrophilic addition of the intramolecular double bonds and condensation reaction of the acid matrix of the linear camellia ternata.2.molecular weight of all derivatives by IR、1H-NMR、13C-NMR and HRMS spectroscopy data structure for characterization.3.purity of all compounds was determined by HPLC combined evaporative light scattering detector.4.the antimicrobial activity of all derivatives was tested by micro broth dilution method,and the inhibition rate of each compound was calculated by using enzyme labeling instrument to measure its OD value.Result:Thirty-first lophanic acid derivatives were obtained by structural modification,fourteen C-20 carboxylate derivatives 3a-n(yield:85-98%),a primary alcohol derivative 5(yield:83%),eight ether derivatives 6a-h(yield:42-75%),one aldehyde derivative 7(yield:63%)and one dimer derivative 11(yield:23%)were synthesized by nucleophilic substitution of C-20 lophanic acid.Then,three tertiary alcohol acylated derivatives 4a-c(yield:15-75%)and one intracyclic diene derivative 9(yield:54%)were synthesized by acylation of C-13 hydroxyl groups.Two lactone derivatives 8(yield:90)and 10((yield:92%)were obtained by intramolecular double bond synthesis.The purity determination results showed that the purity of all 31 lophanic acid derivatives was higher than 95%.The antibacterial activity of all derivatives against T.rubrum,T.mentagrophytes,C.neoformans,S.sobrinus,E.coli and MRSA at 100 μg/mL concentration showed that the inhibition rate of compound 3b on T.mentagrophytes,C.neoformans was greater than 90%,and the inhibition rate of compounds 3d,3e,6c and 6h on T.mentagrophytes was greater than 85%.Compounds 3b,3d,6c and 6h had a good antibacterial effect on MRSA,and the inhibition rate was higher than 95%.Conclusion:All 31 lophanic acid derivatives were new compounds.Compound 3b had better antibacterial activity against T.mentagrophytes,C.neoformans and MRSA,and compounds 3d,6c and 6h also had obvious antibacterial effect against MRSA.More importantly,by comparing the bacteriostatic activity of C-20 carboxyl group,C-13 hydroxyl group and intramolecular double bond derivatives,this paper confirms that the C-20 carboxyl group is the active structural units,which is preliminarily speculated as the active sites of this compound.