| Photodynamic therapy (PDT) is a kind of new technology to diagnose and treat of diseases using photodynamic effect. Photo sens itizers are important material of PDT.5-aminolevulinic acid and its derivatives, the second generation photodynamic drugs, are the hottest point for the developing of photodynamic drug. In this thesis, the synthesis of 5-arninolevulinic acid and its derivatives were studied, and the synthetic route was optimized and improved. The main work in this thesis was as follows:The synthesis of 5-arninolevulinic acid using levulinic acid as the starting materia were studied. The progresses mainly include three reaction steps:the first step was bromination reaction, the second was Gabriel reaction and last was hydrolysis reaction using hydrochloric acid as the solvent.Levulinic acid was brominated with MeOH as solvent to give methyl 5-bromolevulinic acid. The bromination mixtures were qualitatively analyzed by GC-MS and quantitatively analyzed by GC. The highest yield was 59.4%. The optimal conclusions were as follows:n(Br2):n(LA) 1:1, temperature 30℃, reaction time for 6 h, Bromine drops adding was 12 min/ml.Methyl 5-bromolevulinic acid is treated with potassium phthalimide in DMF as solvent, giving intermediate methyl 5-phthalimido levulinate and the reaction yield was 81%. The optimal conclusions were as follows: the molar ratio of K2CO3 and phthalimide and Methyl 5-bromolevulinic acid was 1.5:1.3:1, temperature was 40℃, reaction time was 3 h. Methyl 5-phthalimido levulinate was hydro lyzed with HCl to get 5-arninolevulinic acid and the reaction yield was 78.1%. The optimal conclusions were as follows:reaction time was 12 h and the concentration of HCl was 7 M.The synthesis of 5-Aminolevulinic Acid ester derivatives were prepared directly by esterification reaction using 5-Aminolevulinic Acid and alcohol. ALA methylester, ALA propylester, ALA n-butylester, ALA hexylester were made by this method, the reaction yield were 67.4%, 61.2%,83.5% and 73.8% respectively. |
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