Study On Bioactive Components Of Myristica Fragrans Houtt And Their Chemical Transformations

This thesis is composed of three chapters:Chapter 1 is about the chemical constituents and biological activities of Myristica fragrans Houtt.;Chapter 2 represented the synthesis of natural product myristriol（10）;Chapter 3 summarized the research progress in chemical conversion of phenylpropanoid compounds.In the chapter 1,the chemical constituents of M.fragrans were separated and purified by silica gel,reversed phase silica gel,gel,preparative thin layer chromatography and semi preparative high performance liquid chromatography,and their structures were identified by NMR,MS,IR,ECD and other spectroscopic methods.Finally,52 compounds were isolated from the petroleum ether and the ethyl acetate extracts of M.fragrans,including 5 new compounds（Compound 10 is a phenylpropanoid compound,compound 35 is an aryltetralin lignans,and compounds 42-44 are heterocyclic compounds）;twelve compounds（compounds 11,12,13,14,31,32,33,34,38,39,40,45）were isolated from this genus for the first time.The types of compounds isolated are phenylpropanoid,lignan,diarylalkane,fatty acid,flavonoid,heterocyclic compound,and others.According to the previous experimental results of the research group,the diarylpropane compounds in M.fragrans exhibited good anti-inflammatory activities.In this study,the inhibitory effects of M.fragrans volatile oil,petroleum ether extracts,ethyl acetate extracts,and 45 compounds on NO production were evaluated by lipopolysaccharide（LPS）-induced RAW 264.7 macrophage cells.The petroleum ether and ethyl acetate extracts showed certain inhibitory activity;compound 38 has strong inhibitory activity on LPS-induced NO production in RAW 264.7 cells with IC₅₀ value of 8.57±0.11μmol·L^-1,significantly stronger than positive control L-NMMA(IC₅₀=11.18±0.46μmol·L^-1),and compound 36 also showed a good inhibitory activity with IC₅₀ value of 12.01±1.27μmol·L^-1,which was close to the positive control.In addition,antifungal and anti-hepatitis B virus activities of isolated heterocyclic compounds were also studied.As a result,all compounds tested had no effect on sensitive and resistant strains of Candida albicans;at the same time,the combination of these heterocyclic compounds with fluconazole also showed no synergistic antibacterial effect on fluconazole-resistant Candida albicans.These compounds also had no inhibitory effect on HBs Ag.In the chapter 2,myristriol（10）is a new natural product isolated.The planar structure of 10 is determined by spectroscopic analysis.It is found that there may be two relative configurations for its C2/C3,namely,erythro-configuration and threo-configuration.Through chiral HPLC analysis,it was found that 10 was resolved as a pair of 1:1 enantiomers,and then determined as racemates.Therefore,in order to confirm whether the relative configuration of C-2/C-3 of compound 10 is erythro-configuration or threo-configuration,we utilized an abundant compound myristicin（1）as the starting material to prepare erythro-10 and threo-10 through Pd Cl₂ catalyzed double-bond transposition,Shibuya’s allyl oxidation,Luche reduction,Sharpless dihydroxylation,and other reactions.Finally,the relative configuration of C2/C3 in natural product 10 was determined to be etythro-configuration by comparison the spectroscopic data of synthetic erythro-10 and threo-10with those of natural 10.In the chapter 3,the chemical conversion of phenylpropanoid compounds was reviewed.