Chemical Synthesis Of Novel γ-Butyrolactone Compounds And Preliminary Anti-inflammatory Activity Study

Objective:Many natural products that appear in the natural product have a basic core skeleton that contains aγ-lactone ring.Compounds containing aγ-butyrolactone ring generally exhibit a wide variety of biological activities.The purpose of this study was to design and synthesize compounds with multiple core skeletons asγ-lactone rings and detect their anti-inflammatory activity.Methods:Based on previous laboratory studies on halogenated lactones,this study designed 24 deactivated olefins 2a²x（α,β-unsaturated enones）,through the halogenation of 2a²x,a total of 28 novelγ-butyrolactone derivatives were obtained.The anti-inflammatory activity ofγ-butyrolactone derivatives was detected by reducing ROS and NO levels in RAW 264.7 cells.Results:1.24 novel deactivated olefins 2a²x（α,β-unsaturated enones）and 28 novelγ-butyrolactone derivatives were synthesized.A total of 62 new compounds were synthesized and the structures were all subjected to ¹H-NMR and ¹³C-NMR structures.It was confirmed that deactivated olefins（α,β-unsaturated enones）can also be brominated to giveγ-lactone rings and the yield is extremely high.2.Activity test results:（1）The target compounds 3h can significantly reduce ROS levels in RAW 264.7cells;（2）The target compound 3h and 3y can significantly reduce the NO level in RAW 264.7 cells.Only the dose of 3y-1 reaches 20mM,the NO level in RAW 264.7cells can be decreased,and ent-3h had no significant effect on the two assays.ConclusionExperiments have shown the compounds of theγ-butyrolactone ring structure are novel,simple synthesis method,high yield,and good anti-inflammatory activity.It has also been demonstrated that inactive olefins（α,β-unsaturated enones）can also be halogenated lactones into rings.And compounds 3h can be used as potentially potent anti-inflammatory agents.The structure of 24 novelα,β-unsaturated enones and 28novelγ-butyrolactone derivatives was confirmed by ¹H-NMR,¹³C-NMR and HRMS.