Studies On Synthesis And Antibacterial Activity Of Magnolol Derivatives

Magnolol is one of the main active components in Magnolia officinalis,which has a wide range of biological activities.The chemical structure of magnolol is diallyl substituted biphenol.Modifications on the magnolol’s phenolic hydroxyl and benzene group have been reported in many studies for a long time.However,synthesizing and biological activities research of allyl-modified magnolol derivatives were very few.In this paper,a series of magnolol derivatives were synthesized by phenolic hydroxyl substitution,phenyl substitution and allyl-oxidized.Then using magnolol as the positive control,the antibacterial activity of the synthesized magnolol derivatives were tested and discussed.The main researches contents are given as follows:1.Starting from magnolol and eugenol,a series of hydroxyl substituted and phenyl substituted magnolol derivatives were obtained.Then we oxidated allyl groups in the structure of magnolol derivatives to obtain the corresponding oxidanted magnolol derivatives.In this step,we found one efficient way to oxidate allyl to acrolein in the structure of magnolol derivatives with DDQ（2,3-Dichloro-5,6-dicyano-1,4-benzoquinone）.Through exploring the reaction conditions by using p-phenyl allylbenzene as the template,establishing the new reaction condition:0.2 equivalent of DDQ,oxygen and 0.2 equivalent of tert-butyl nitrite（^tBu ONO）as the combined oxidation catalysts,2.0 equivalent of H₂O,nitromethane（CH₃NO₂）as the solvent,stirred at 60℃for 24h.Finally,p-phenyl acroleinbenzene was obtained in the yield of 72%and the purity is over 95%.The structure and purity of each compound was verified by NMR analysis.Conforming the standards for the antibacterial activity research.2.The antibacterial activities of magnolol derivatives against Staphylococcus aureus,Escherichia coli,Enterococcus faecalis and Streptococcus agalactiae were determined by oxford cup method.The results showed that magnolol presented certain antibacterial activities against Staphylococcus aureus,Enterococcus faecalis and Streptococcus agalactiae,but do not against Escherichia coli.3,3’-di-O-allyl-5,5’-diacrolein magnolol（compound L）showed the better antibacterial effect on Staphylococcus aureus,slightly higher than magnolol,and it is also showed the better antibacterial effect on Enterococcus faecalis at the same time.2,2’-di-O-acetyl-3,3’-dimethoxy-5,5’-diacrolein magnolol（compound R）showed the better antibacterial effect on Escherichia coli.3,3’-dimethoxy-5,5’-diacrolein magnolol（compound S）showed the better antibacterial effect on Streptococcus agalactiae.The experimental results speculated that magnolol derivatives with acrolein on the structure of benzene may has better inhibitory effects on Gram-positive bacteria,and with allyl on the structure of the benzene may has better inhibitory effects on Gram-negative bacteria.