Synthesis And Bioactivities Of Nitroxide Radiocals Spin-labeled Derivatives Of ?-Tocopherol,Salidroside And Resveratrol

?-Tocopherol, Resveratrol and Salidroside belong to pherols and glycosides, found in plants. These natural products possess a variety of bioactivities, such as anti-titumor, anti-inflammatory, antioxidant, radioresistance and so on. The researchers' attention for radioprotective property of these compounds has been attacted. And theirs natural structures have served as a foundation used to developing many novel drugs and studying its pharmacological activities. In recent years, a stable nitroxide free radicals, which have the characteristics of electron spin resonance, have been discoveried. This kind of compounds and its derivatives also possess antioxidant(superoxide dismutase mimic), anticancer and radioresistance. At present,it is reported that not only was the toxicity of spin-labeled natural products reduced, but also the bioactivities were improved. At the same time, spin labeling has been used for determining drug targets and mechanism in vitro and in vivo. To prepare a high efficiency and low toxicity radioprotective agents, we designed and synthesized spin-labled derivatives of ?-Tocopherol, Resveratrol and Salidroside.There are four chapters in my thesis:In chapter one, the radioprotective bioactivity of natural polyphenols, polysaccharide, flavonoids and saponins was introduced. The research progress of ?-Tocopherol, Resverate, Salidroside and nitroxides were reviewed, respectively.In chapter two, the synthetic route of spin-labeled ?-Tocopherol was designed and the target compound was prepared. Firstly, the substituent with aldehyde group was imported into ?-Tocopherol through esterification reaction. Secondly, the product of this reaction cyclize with 2, 3-bis(hydroxyamino)-2,3-dimethylbutane. Thirdly, the target compound was obtained by oxidizing product of the second step reaction.In chapter three, the synthetic route of spin-labeled Salidroside was designed and the target compound was prepared. The target compound was synthesized through nucleophilic substitution reaction of Salidroside with the intermediate compound, 4,4,5,5-tetramethyl-2[4'-(2-bromoethoxy)] phenyl-1-ox-3-oxyl-imidazoline.In chapter four, the last spin-labeled derivatives of Resveratrol were designed and synthesized. Firstly, the substituent with aldehyde group was imported into Resveratrol through nucleophilic substitution reaction of Resveratrol with 4-(2'-bromoethyoxyl)benzaldehyde in alkaline conditions. The intermediates compounds, R-1a, R-1b and R-1c, were obtained. Secondly, These three derivatives' aldehyde group react with 2,3-bis(hydroxyamino)-2,3-dimethyl- butane and such step products were oxidated by sodium periodate or lead peroxide. Purifying the spin-labeled derivatives of Resveratrol, the target compounds were prepared.In my thesis, HPLC, HR-MS, IR, 1HNMR, 13 CNMR, EPR was used to characterize the intermediates and target compounds. The cytotoxic and antioxidant activity of new compounds was preliminarily evaluated and two low toxicity of spin labeling derivatives were filtered out?A-3 and S. These two kinds of compounds' IC50 are 549.14 ?M, 119.23 ?M(lymphocyte), respectively. IC50 of S exceeds 347.67 ?M(HL-60). At the same time, the spin-labeled derivatives(A-3 and S) would be used to evaluate the radioprotective activity in vitro.