Synthesis And Purification Of New Antihypertensive Drug Brown Algae Amino Acid

High blood pressure can lead to the disease of kidneys and heart, having serious harm to human beings health, and has already become the "number one killer". In recent years, due to the changes in human’s lifestyle and diet, the incidence of hypertension in young groups has also been increasing year by years. Brown algae amino acid is a kind of amino acid rarely existing in brown algae, which having a good effect on the prevention and treatment of hypertension. At present, the brown algae amino acid is not listed at home and abroad and is likely to become an effective and non-toxic new marine antihypertensive drug. Brown algae amino acid accounts only three over ten thousand in the brown algae. If this amino is extracted from brown algae, the cost of this method will be too much and will cause enormous waste. In this topic, the low toxic substance—dimethyl carbonate was used as methylating reagent and the preparation technology of lysine metal(zinc, copper) chelate and brown algae amino acid was explored. The research mainly included the preparation process optimization of zinc lysine chelate and lysine copper chelate, and the best DMC methylation in both atmospheric pressure and the high-pressure atmosphere has also been explored. The single factor and response surface experiments was used respectively to optimize the best preparation process of lysine zinc chelate and three methyl lysine zinc, and the pure brown algae amino acid was obtained by a variety of purification methods. The product was identificated by TLC, IR, melting point determination, HPLC and liquid MS analysis methods. The aim of this research is to obtain a synthesis route of brown algae amino acid with high yield rate and purity, vigorously promoting the China marine drug development and achieving effective industrial production of antihypertensive drug brown algae amino acid in large scale.Firstly the metal chelating experiment was adopted to protect the a-lysine amino, and the stability of two lysine metal chelate(lysine zinc chelated and lysine copper chelated) was compared. The best experimental conditions of lysine zinc and lysine copper was explored by single factor experiments and the system pH, reaction temperature and reaction time was identified as the largest experimental influence factors. On this basis, the response surface method was used to optimized the best synthesis crafts of lysine zinc chelate and the best synthesis conditions was obtained:the system pH of 7.5, the reaction temperature of 58 ℃, the reaction time of 2h, and the best reaction yield is 93.17%. Then DMC was choosed as the methylating reagent for lysine zinc methylation reaction. The best experimental conditions of DMC methylation reaction both in atmospheric pressure and the high-pressure atmosphere was explored by single factor experiments and the reaction temperature, stirring speed and the amount of potassium carbonate was found to be the largest impact factors of experiment. On this basis, the response surface method was used to optimized the best synthesis crafts of lysine zinc methylation reaction and the best synthesis conditions was obtained:the reaction temperature of 160℃, the stirring speed of 380r/min, the potassium carbonate using amount of 3.8%, and the best reaction yield is 45.52%, nearly double the previous reaction yield.Finally, the 732 alginic acid cation exchange resin was used to separate and purify the crude product. In order to get brown algae amino acid crude product, the brown algae amino acid reaction solution was isolated by distillation, extraction, column chromatography and crystallization methods. The static adsorption single factor experiments was used to explore the separate conditions of ion exchange chromatography and the best synthesis conditions was found:the initial elution pH of 12.5, the resin volume of 30ml, the experiment time of 30min, the adsorption temperature of 25 ℃, the best elution pH of 12.5. On this basis, the product was purified by dynamic adsorption experiments. By using thin layer chromatography, melting point determination, HPLC and LC-MS and IR spectra methods, the final product was confired as brown algae amino acid.