(r)-alpha-lipoic Acid On The Synthesis Of New Technology And Bactericidal Activity

α-Lipoic acid can exist in R and S forms. The R-isomer is responsible for physiological function. (R)-α-Lipoic acid is an essential coenzyme in the oxidative dacarboxylation ofα-keto carboxylic acids. The limitations of traditional synthetic methods of (R)-α-lipoic acid include high cost and difficulty in utilization of invalid body. It is of great importance to develop a low-cost process for the preparation of (R)-α-lipoic acid. According to literatures, a new synthetic method for the preparation of (R)-α-lipoic acid was resigned. Antifungal activity of (R)-α-lipoic acid was tested firstly.Starting from ethyl 6-hydroxy-8-chlorooctanoate, (R)-α-lipoic acid was synthesized in six steps including hydrolysis, resolution, esterification, chloration, hydrolysis and substitution. The structures of intermediates and product were characterized by element analysis, IR and NMR. The reaction was monitored and quantitatively analysed by gas chromatography. Every step in the scheme was discussed in detail. The controlling reaction factors, such as molar ratio, temperature, adding time, catalyst, solvent were carefully analysed mainly in the resolution, chloration and substitution reactions. The optimized parameters were as follows: In the chiral resolution, the reactants molar ratio of [6-hydroxy-8-chlorooctanic acid : (R)-α-phenylethylamine] was 1 : 0.48, reaction temperature was 35°C. For the chloration reaction with catalyst, the reactants molar ratio of [(S)-ethyl 6-hydroxy-8-chlorooctanoate : thionyl chloride] 1 : 1.4, reaction temperature 35°C, and solvent petroleum ether were employed. In absence of catalyst, the reactants molar ratio of [(r)-ethyl 6-hydroxy-8-chlorooctanoate : thionyl chloride] 1 : 1.4, solvent petroleum ether, and a reaction temperature of 65°C were formed most suitable. In the substitution reaction, a molar ratio of (R)-dichlorooctanic acid to sodium disulfide 1 : 1.2, the reaction temperature 75°C, and adding time of 3.0 h provided the best result. The total yield of (R)-α-lipoic acid was 30%.Compared with traditional methods, both (5) and (R)-ethyl 6-hydroxy-8-ohlorooctanoate were converted into (R)-ethyl 6,8-dichlorooctanoate. The invalid body was utilized effectively with a reduction of cost. Antifungal activity of (R)-α-lipoic acid was tested and the result showed that it possessed high antifungal activity on three plant pathogenic fungi in vitro, which was parallel to Hymexozole at 500μg/mL.