Study On The Antioxidant Activity Of Two Types Of Natural Neolignans And1,2,4-oxadiazole Derivatives

Recently, study on antioxidant activity of natural antioxidants, including thesynthesis of natural antioxidants, was one of the central issues in physical organicchemistry. This thesis focused on three types of compounds, such as honokiol andmagnolol, ailanthoidol and related products, and1,2,4-oxadiazole derivatives. Tencompounds were prepared with different types and positions of substituents attached,and their antioxidant activities were studied.A variety of methods was employed to evaluate the antioxidant activity ofantioxidants, such as conjugated diene hydroperoxide method, chemiluminescencemethod, thiobarbituric acid method,2,2’-azinobis-3-ethylbenzthiazoline-6-sulfonicacid diammonium salt method,2,2-diphenyl-1-picrylhydrazyl method, galvinoxylmethod, ferric reducing antioxidant power method, and cyclic voltammetry method.Different methods were based on different principles, where each method showsseveral distinct features of the antioxidant under different conditions. But eachmethod has its own disadvantages and limitations. So far, there is no standard testingmethod for measure the total antioxidant capacity exactly in biological systems.Therefore, comprehensive assessment of various methods should be applied toapproach a satisfactory result.Present herein are free radical scavenging methods and inhibitory effect on lipidperoxidation applied to evaluate the antioxidant activites, and to comprehensively andsystematically study on the antioxidant activity of three types of antioxidants.Chemical kinetics were employed to treat the collected results from radicalscavenging. It leads to a new way to get antioxidant activites reliably and intuitively.The major work in this thesis has been carried out as the following aspects:1. Studies on the isolation of honokiol and magnolol and the evaluation of antioxidant activitiesA facile purification method was employed to isolate honokiol and magnolol.The comparison of their antioxidant actions and the influence of the position ofhydroxyl group on antioxidant capacity were explored in the experimental systems ofscavenging ABTS+, DPPH and galvioxyl free radicals, reducing1O2and ONOO-,bleaching β-carotene in linoleic acid and inhibit the oxidation of DNA induced byAAPH, Cu²⁺/GSH, and OH.Both honokiol and magnolol have strong antioxidant activities. Honokiol showedhigher activity to trap ABTS+and DPPH, to protect LH, and to inhibit AAPH-,Cu²⁺/GSH-and OH-induced oxidation of DNA than magnolol. The obtained resultssuggested that low antioxidant ability of magnolol may be related to theintramolecular hydrogen bond formed between di-ortho-hydroxyl groups, whichhindered the hydrogen atom in hydroxyl group to be abstracted by radicals. Therefore,the antioxidant capacity of magnolol was lower than that of honokiol. Both honokioland magnolol can reduce1O2and ONOO-. Unfortunately, honokiol and magnolol cannot trap galvinoxyl radical.2. Studies on synthesis and antioxidant activities of ailanthoidol and its modifiedproductAilanthoidol was synthesized by intramolecular Wittig reaction. Furthermore,ailanthoidol was modified by aldol reaction as a key step, a ferrocenyl group was usedto substitute the alcoholic hydroxyl group to form（E）-1-ferrocenyl-3-（2’-（4”-hydroxy-3”-methoxyphenyl）-7’-methoxybenzofuran-5’-yl）prop-2-en-1-one （FBF）. The effect of the alcoholic hydroxyl group and ferrocenemoiety on antioxidant capacity was explored in the experimental systems ofscavenging ABTS+, DPPH and Galvioxyl free radicals and inhibit the oxidation ofDNA induced by AAPH, Cu²⁺/GSH, and OH.The alcoholic hydroxyl group in ailanthoidol is not the antioxidant group.Ailanthoidol showed higher activity to trap DPPH and to inhibit Cu²⁺/GSH-and OH-induced oxidation of DNA than FBF. But ferrocenyl group enhances the abilityof ferrocene-appended ailanthoidol to scavenging ABTS+and to protect DNA againstAAPH-induced oxidation. Ailanthoidol and FBF can not trap galvinoxyl radical.3. Studies on synthesis and antioxidant activities of1,2,4-oxadiazole derivativesSix3,5-diaryl-1,2,4-oxadiazole derivatives were synthesized by cyclization as akey reaction. The antioxidant activity which derived from the interaction betweendiaryl groups and1,2,4-oxadiazole moiety was explored in the experimental systemsof scavenging ABTS+and DPPH and inhibit the oxidation of DNA induced by AAPH,Cu²⁺/GSH, and OH.In the presence of a vanillin group at A ring,1,2,4-oxadiazole derivative exhibitshigh antioxidant properties. Vanillin group or o-hydroxyl phenyl group as the B ring,compared with phenyl group, can enhance antioxidant activities, especially,o-hydroxyl phenyl group showed the highest activity to trap ABTS+and DPPH.Accordingly, the n value in protecting DNA against AAPH-induced oxidationprovided an order for antioxidant effectiveness as4-（5-（4-Hydroxy-3-methoxyphenyl）-1,2,4-oxadiazol-3-yl）-2-methoxyphenol （HMOP）>4-（5-（2-Hydroxyphenyl）-1,2,4-oxadiazol-3-yl）-2-methoxyphenol （2HOP）>4-（5-（2-Chlorophenyl）-1,2,4-oxadiazol-3-yl）-2-methoxyphenol （CHOP）>2-Methoxy-4-（5-（pyridin-3-yl）-1,2,4-oxadiazol-3-yl）phenol （PYOP）>4-（5-（3-Hydroxyphenyl）-1,2,4-oxadiazol-3-yl）-2-methoxyphenol（3HOP）²-Methoxy-4-（5-phenyl-1,2,4-oxadiazol-3-yl）phenol （PHOP）. An ortho-chloro group even possessed the highest ability to inhibit OH-induced oxidation ofDNA and the lowest ability to inhibit Cu²⁺/GSH-induced oxidation of DNA, while ameta-hydroxyl group at B ring acted as an efficient antioxidant factor to protect DNAagainst Cu²⁺/GSH-induced oxidation and an inefficient antioxidant factor to trapABTS+.