Synthesis,characterization,Whitening And Anti-oxidant Activities Of Phenolic Nitrogen-containing Derivatives

Phenols and polyphenols show a variety of biological activities,such as whitening,anti-oxidation,anti-cancer,anti-inflammatory,and anti-allergy.Representative compounds are tea polyphenols,quercetin,resveratrol,salidroside and arbutin.Phenolic hydroxyl groups'number,position and different side chain are important to activitiesTo further study of the structure-activity relationship of phenolic nitrogen-containing derivatives.Based on the combination principle,this paper used p-hydroxybenzaldehyde,4-hydroxy-3-methoxybenzaldehyde,3,4-dihydroxybenzaldehyde,p-hydroxyphenylethanol and 3-(4-hydroxyphenyl)-1-propanol as starting materials,structurally modificated by inducing nitrogen-containing moiety to increase polarity,in order to obtain better whitening,anti-oxidant activity and low toxicity compounds.There are three parts in this dissertation:The first part:The biological activities of phenols and phenolic compounds were reviewed.The applications of nitrogen-containing compounds such as amino acids,morpholine and piperazine in the field of medicine were also introduced.The second part:Design,synthesis and characterization of phenolic nitrogen-containing derivatives.We synthesized 26 compounds,24compounds have not been reported.1.Using p-hydroxybenzaldehyde,4-hydroxy-3-methoxybenzaldehyde,3,4-dihydroxy-benzaldehyde,p-hydroxyphenylethanol and 3-(4-hydroxyphenyl)-1-propanol as starting materials.Five intermediates HB-1,HMB-1,DHB-1,HPE-1 and HPP-1 were obtained by phenolic hydroxyl protection.2.HB-2,HMB-2 and DHB-2 were synthesized by aldehyde group reduction of HB-1,HMB-1 and DHB-1.Three intermediates were prepared by reacting HB-2,HMB-2 and DHB-2 with methanesulfonyl chloride respectively.Because of the instability of the intermediates,they were not further purified and directly used in the next reaction.Six phenolic nitrogen-containing derivatives HB-3(a,b),HMB-3(a,b)and DHB-3(a,b)were synthesized by coupling the three intermediates with morpholine and N-methyl piperazine and removing acetyl groups.3.HPE-2(a,b)and HPP-2(a,b)were obtained by coupling two N-Boc amino acids with hydroxyl groups of HPE-1 and HPP-1,then HPE-3(a,b)and HPP-3(a,b)were obtained by removing benzyl protecting group,after removing the Boc protecting groups we get four target compounds HPE-4(a,b)and HPP-4(a,b).Twenty-four new compounds were characterized by IR,¹H NMR,¹³C NMR and ESI-MS.The third part:The tyrosinase inhibitory activity of twenty-four new compounds was tested.The results indicate that eight compounds HB-1,HB-3a,HB-3b,HMB-3a,HMB-3b,HPE-2b,HPE-3b and HPE-4b had inhibition to tyrosinase and six compounds of them against tyrosinase are better than positive control of?-Arbutin.The anti-oxidant activity of eight compounds with tyrosinase inhibitory activity was tested.The results showed that HB-3a,HB-3b,HMB-3a,HMB-3b,HPE-2b,HPE-3b and HPE-4b had anti-oxidant activities,and the anti-oxidant activities of HB-3b and HMB-3a were equally as well positive control of quercetin and lycopene.