Synthesis Of Curcumin Derivatives And Studies On The Antioxidant Activity

In recent years, the total synthesis of natural products and the studies on their antioxidant activity is one of the hot topic in organic chemistry research. In this work, we selected curcumin as the research object, and synthesized a variety of compounds to it and half-curcumin as a precursor, and then curried out a study on their antioxidant activity.The methods to evaluate antioxidant activity are usually defined as two types: chemical systems and chemical simulation biological systems. The former is mainly used for rapid quantitative determination of the strength of antioxidant activity. But because of the difference between chemical-mimic biological systems, the results from the chemical systems can not be directly characterized as biological antioxidant activity, the latter will overcome these problems to some extent. In this work, the kinetic equation of chemical is introduced into chemical simulate of biological systems, which can be used in biological system to evaluate the activity of antioxidants quantitatively. Main works are as follows:1. Synthesis and studies on antioxidant activity of several major materialsThe testing on the antioxidant activity of several materials are carried out, and it is the basis for discussion in further experimental results.Protocatechualdehyde and 4-Benzyloxy-3-methoxybenzaldehyde are synthesized in this part. Then the antioxidant activity of Protocatechualdehyde, Vanillin and Acetylacetone are determined by using antiradical assays against 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, galvinoxyl radical, and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS+.) and by protecting DNA against 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) induced oxidation.The results revealed that these compounds have antioxidant activity to a certain extent, especially vanillin and protocatechuic aldehyde have a strong ability to the protect DNA against AAPH-induced oxidation.2. Synthesis and studies on antioxidation activity of curcumin and its derivativesThe aim of this work is to clarify the antioxidant abilities of phenolic and enolic hydroxyl groups in curcumin. 1,7-Bis(4-benzyloxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (BEC), 1,7-bis(4-hydroxy-3-methoxyphenyl)heptane-3,5-diol (OHC), 1,7-bis-(4-hydroxy-3-methoxyphenyl)heptane-3,5-dione (THC), and 1,7-bis(3,4-dihydroxyphenyl)-1,6-heptadiene-3,5-dione (BDC) are synthesized to determine the antioxidant activities by using antiradical assays against DPPH radical, galvinoxyl radical, and ABTS+. and by protecting DNA and erythrocyte against AAPH induced oxidation. The molecularstructure of curcumin and its derivatives are outlined in Figure 1.The phenolic hydroxyl is the main group for curcumin to trap DPPH, galvinoxyl and ABTS+. radicals. The conjugative system between enolic and phenolic hydroxyl groups is beneficial for curcumin to protect erythrocytes against hemin-induced hemolysis and to protect DNA against AAPH-induced oxidation, but is not beneficial for curcumin to protect erythrocytes against AAPH-induced hemolysis. More hydroxyl groups enhance the antioxidant effectiveness of curcumin in the experimental systems employed herein. Therefore, curcumin acts as an antioxidant through the phenolic hydroxyl group. In addition, compared with the raw materials, the antioxidant activities of curcumin and its derivatives have been strengthened.3. Synthesis and studies on antioxidant activity of half-curcumin and its derivatives The main purpose of this work is to clarify the antioxidant abilities of phenolic and enolic hydroxyl groups in half-curcumin, and the difference form that of curumin.Half-curcumin(Feruloylacetone), 6-(4-benzyloxy-3-methoxyphenyl)-5-he-xene-2,4-dione(BMFT), 6-(3,4-dihydroxyphenyl)-5-hexene-2,4-dione(DDFT), ethyl 2-(4-hydroxy-3-methoxybenzylidene)-3-oxobutanoate(EOFT), 6-(4-h-ydroxy-3-methoxyphenyl)hexane-2, 4-dione(DHFT), and 6-(4-hydroxy-3-met-hoxyphenyl)-5-hexene-2,4-diol(THFT) are synthesized to determine the anti-oxidant activities by using antiradical assays against DPPH radical, galvinoxyl radical, ABTS+., and 1O2 radical;β-carotene-bleaching; theprotection of methyl linoleate against AAPH-induced oxidation; protecting DNA againstAAPH, Cu2+/GSH, .OH-induced oxidation; and by protecting erythrocyte against AAPH, hemin-induced oxidation. The molecular structures of half-curcumin and itsderivatives are outlined in Figure 2.The results express that it is easy for FT,DDFT,DHFT and EOFT to donate H atom to N-centered radicals while the H atom in THFT can donate to O-centered radicals easily, and the antioxidation activities of half-curcumin and its derivatives are weaker than that of curcumin and its derivatives. In addition to the prooxidant role of half-curcumin in Cu2+/GSH-induced oxidation of DNA, half-curcumin used to behave as antioxidant, whose abilities are devoted to the reductive and radical-scavenging properties due to phenolic and enolic -OH. The enolic -OH does not possess any antioxidant property, and even promotes hemin-induced hemolysis. The antioxidant activity of phenolic -OH is not obvious either. The phenolic and enolic -OH contained in the same molecule enhances the antioxidant efficacy significantly when they are not connected by a conjugative system. Meanwhile, enolic -OH tautomerized fromβ-keto ester cannot increase the antioxidant ability of half-curcumin. Finally, more phenolic -OH increases the antioxidant capacity remarkably.