Synthesis,Characterization And Study On Biological Of Phenolic Nitrogen-containing Conjugates

Arbutin and salidroside are significant phenolic derivatives.Arbutin is a hydroquinone glucoside compound existing in various plants.It is widely used in pharmaceutical and cosmetic industries owing to its well-known skin-lightening property as well as anti-oxidant,anti-microbial,and anti-inflammatory activities.Salidroside is one important medicinal ingredient of Rhodiola rosea L,has multiple pharmacological effects,such as anti-cancer,anti-inflammatory and anti-oxidative properties,etc.Their biological activities are usually related to phenolic hydroxyl groups,and the introduction of nitrogen-containing fragments usually improves the bioavailability of drugs.At the same time,the position of phenolic hydroxyl groups and the length of the linkage will also affect the biological activity of the compound.Therefore,the dissertation used hydroquinone,catechol,2-(4-Hydroxyphenyl)ethanol and 3-(4-Hydroxyphenyl)-1-propanol as starting materials,through the protection of one side phenolic hydroxyl,then coupled with morpholine,N-methylpiperazine and N-Boc-ethylenediamine,last,removed the protecting groups to get twenty-five unreported compounds.The inhibitory activity of tyrosinase was tested on 25 compounds and 19 compounds were tested for anti-microbial activities,in order to get compounds with better biological activity.This dissertation is divided into three parts:Part ?:Reviewed the biological activities of arbutin and salidroside,and introduced the nitrogen-containing compounds such as piperazine.Part ?:Described the design,synthesis and characterization of phenolic nitrogen-contai-ning conjugates.1.Using hydroquinone,catechol,2-(4-Hydroxyphenyl)ethanol and 3-(4-Hydroxyphenyl)-1-propanol as starting materials.Through the protection of one side phenolic hydroxyl,we get four different key intermediates(p-HQ-2,o-HQ-2,S-2,L-2).2.With the other side phenolic hydroxyl of p-HQ-2 and o-HQ-2 coupling with methyl bromoacetate and reduction,we get two alcohol intermediates(p-HQ-4,o-HQ-4).3.The key intermediates p-HQ-5,o-HQ-5,S-3 and L-3 were obtained by the reaction of p-HQ-4,o-HQ-4,S-2 and L-2 with methanesulfonyl chloride,respectively.Then p-HQ-5,o-HQ-5,S-3 and L-3 were coupled with morpholine,N-methylpiperazine and N-Boc-ethylenediamine,and 12 compounds[p-HQ-6(a-c),o-HQ-6(a-c),S-4(a-c),L-4(a-c)]were obtained.4.Nine kinds of phenolic nitrogen-containing conjugates[p-HQ-7(a-c),o-HQ-7(a,c),S-5(a-c),L-5a]were obtained by the remove of benzyl group of[p-HQ-6(a-c),o-HQ-6(a,c),S-4(a-c),L-4a].25 new compounds were characterized by IR and ~1H NMR.Parts of compounds were characterized by ESI-MS spectrometer and measured value coincide with theoretical value.Part ?:25 compounds in vitro inhibition activities towards tyrosinase were evaluated and the results indicate that p-HQ-6b,p-HQ-6c,p-HQ-7a,p-HQ-7b,S-4b,S-4c,S-5a,S-5b,L-3,L-4b,L-4c and L-5a had inhibition to tyrosinase,and 11 compounds of them against tyrosinase are better than positive control a-Abutin.The antimicrobial activities of E.coli1628,S.a 4220 and S.m 3065 were tested for 19 compounds.The results showed that p-HQ-6c had antimicrobial activity on the above three kinds of bacteria.