Study On The Synthesis And Antidepressant Bioactivity Of 4-O-Syringaresinol Derivatives

Cortex Albizziae,originated from the bark of the leguminous plant Albizzia Julibrissin Durazz.It has lots of functions,such as mind-tranquilizing,antitumor,swelling and regulating the body's immune.It is also used to treat depression and insomnia on TCM clinic.Existing studies have found that lignans' extracts from Cortex Albizziae are full of activity of antianxiety.(-)-Syringaresinol-4-O-?-D-glucopyranoside has been found with high activity of antianxiety by Professor Guoping Gan,from School of Pharmaceutical Sciences,Hubei University of Chinese Medicine.Taking the finiteness of extracting activity compounds from natural drugs and plants into account,we hope that it could make extracts as a lead compound,in order to find the sedative compound for clinical research which was effective and have few side effects.Purpose Taking the limitation of natural drugs with active ingredient content sources extracted from plants into account,the whole process needs lots of work,and it's inefficient.Researches of these compounds are limited both in domestic and overseas.Furthermore,synthesis of glucopyranoside is a difficult part.Here,we use simple benzaldehyde derivatives as the originalmaterial,in order to design and synthesis 4-O-syringaresinol as the important intermediate.The synthesis route has been improved efficiently;meanwhile,we will carry out structure modification for 4-O-syringaresinol.We also try to synthesis a little glucopyranoside in order to open a new way for the synthesis of glucopyranoside.By means of screening the anxiolytic activity of each compound,evaluating them separately,compounds which get optimal activity will be selected.Furthermore,the preliminary antidepressant activity of these compounds on mice will be studied.We also wish to establish a platform which is mainly serviced to research and develop lignans,and this platform gives priority to 4-O-syringaresinol.Methods and Results of Research 1.On this article,we search lots of documents in order to determine final synthesis route of 4-O-syringaresinol.We use syringaldehyde as the material,pyridine as the solvent to synthesis trans-sinapic acid with malonic acid through Knovevenagel condensation,trans-sinapic acid will be esterified by ethanol to get unsaturated ester,then hydrogenated by DIBAL-H in a low temperature to get sinapyl alcohol,and oxidative coupling will be conducted by light and air to get 4-O-syringaresinol with excellent form.2.4-O-syringaresinol has been regarded as a parent compound;two phenolic hydroxyls will be decorated by alkylation reaction and acylation reaction to synthesis a series of 4-O-syringaresinol derivatives purposefully,in order to seek the primary relationship between structure and activity.3.We will use acetobromglucose as an active sugar to synthesis syringaresinol-4-O-?-D-glucopyranoside by classic Koenigs-Knorr reaction,and we will not take chiral configurations of compounds into account.Finally,an efficient way for the synthesis of glucopyranoside will be opened primarily.4.We will use the Porsolt method to carry out forced swimming test and mouse tail suspension test,so that we could establish the model of antidepressant pharmacological test and evaluate the antidepressant activity of the synthesized compounds.Primary pharmacological experiments have showed that 4-O-syringaresinol can shorten the immobility time on tail suspension test significantly,which showed significant differences as compared with control group.Because of the time,our experiments had just done some primary work,mechanism of activity was not been researched deeply.However,this also provides a reference for further researches.Conclusion 1.The synthesis route of 4-O-syringaresinol is applied to the general synthesis in laboratory;reagents and materials are cheap and easy to get,experimental conditions are simple,and it's easy to carry out follow-up research.2.The products will be testified by instrumental analysis methods,such as 1H-NMR and 13C-NMR map resolution.The map can show that these compounds have been prepared successfully.3.A new way for the synthesis of glucopyranoside will be opened,which laid a strong foundation for the future work.4.Activity of anti-depression on 4-O-syringaresinol will be proven by primary experiments on mice.