Design,Synthesis And Bioactivity Of Novel Phenylalanine Derivatives

Amino acids and their derivatives have a wide range of biological activities,such as antiviral,antifungal and antibacterial.In this study,two series of novel DL-phenylalanine derivatives were designed and synthesized from DL-phenylalanine on the basis of our previous work.In vitro activity of all target compounds against fungi were tested by mycelial growth rate method,and the EC₅₀ values of high active compounds were further tested.The mechanism of action against fungi was preliminarily explored.The first series of 28 target compounds containing"1,3,4-oxadiazole thioether"moieties were synthesized from DL-phenylalanine through esterification,Boc group protection,hydrazolysis,closed-loop,thioetherification and de-Boc group reaction processes.The second series of 28 dithioether compounds containing"acylhydrazone dithioether"moieties were synthesized through the reaction processes of esterification,hydrazolysis,substitution and thioetherification.The structures of all the target compounds were confirmed by ¹H NMR,¹³C NMR,¹⁹F NMR and HRMS,and the structures of each series of compounds were further determined by single crystal diffraction（X-ray）.Antifungal activities of target compounds against six kinds of plant pathogenic fungi（Thanatephorus cucumeris,Gibberella zeae（Schwein.）Petch,Botryosphaeria dothidea,Sclerotinia sclerotiorum（Lib.）de Bary,Gibberella saubinetii,and Alternaria solani）were carried out in vitro by the mycelium growth rate method,and the results revealed that the target compounds of series I exhibited over 50%inhibition rates against five kinds of fungi at the concentration of 100μg/m L.Among them,six compounds exhibited above 90%inhibition rates against Thanatephorus cucumeris,which was higher than azoxystrobin（90.6%）.The compounds of series II exhibited moderate activities against the six tested fungi.The EC₅₀ value of G₁₀ against T.cucumeris was 31.9μg/m L,and the EC₅₀ value of L₃ against Sclerotinia sclerotiorum was 30.4μg/m L.Preliminary antifungal mechanism study showed that compound G10 can affect the growth of mycelia by destroying the integrity of mycelia membrane,and the higher the concentration of G10,the greater the damage to the integrity of mycelia membrane,thus acting as an inhibition of mycelial growth.