本文關(guān)鍵詞：降血壓藥物—昆布氨酸合成方法的研究　出處：《青島科技大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

  更多相關(guān)文章： 昆布氨酸 賴氨酸銅螯合物 碳酸二甲酯 甲基化 陽離子交換樹脂

【摘要】：高血壓是中老年人群中最常見的心腦血管疾病。近幾年來,由于學(xué)習(xí)、工作、飲食等各方面原因,高血壓也出現(xiàn)在了年輕人群中。海帶(又名褐藻)中含有的昆布氨酸是一種具有降血壓、降血脂的作用的堿性氨基酸,對預(yù)防和治療高血壓和冠心病等心血管疾病作用良好。目前,作為國家一類新藥的昆布氨酸,國內(nèi)外對它的研究都很少,市售的昆布氨酸也還未出現(xiàn)。海帶中昆布氨酸的含量極少,提取的方法造價太高而且會造成很大的浪費,因此不適合工業(yè)化生產(chǎn)。本課題順應(yīng)綠色化學(xué)的要求,以安全低毒的“綠色”試劑碳酸二甲酯為甲基化試劑,采用化學(xué)全合成的方法制備昆布氨酸,并用響應(yīng)面法分析影響螯合反應(yīng)和甲基化反應(yīng)的各種因素以優(yōu)化二者的制備工藝,實現(xiàn)降血壓藥物-昆布氨酸清潔化生產(chǎn)。首先,本課題采用金屬離子螯合法保護賴氨酸中的α-NH2。探索了Ca2+、Mg2+、 Cu2+、Zn2+、Ni2+五種金屬離子分別與賴氨酸的螫合反應(yīng),確定了使用Cu2+對α-NH2進行保護。通過單因素實驗確定影響比較大的因素為反應(yīng)的溫度、時間以及體系pH,并通過響應(yīng)面實驗確定了合成賴氨酸銅的最優(yōu)工藝：反應(yīng)溫度為66℃,反應(yīng)時間為1.5h,pH值為7.5。以最優(yōu)方案合成的賴氨酸銅經(jīng)過80%的乙醇溶液分離提純,產(chǎn)率可達93.15%。其次,選用碳酸二甲酯做甲基化試劑制備ε-N三甲基賴氨酸。通過單因素實驗和響應(yīng)面實驗探索反應(yīng)溫度、時間、催化劑、反應(yīng)體系、相轉(zhuǎn)移催化劑等對甲基化反應(yīng)的影響,優(yōu)化了合成ε-N三甲基賴氨酸的最佳工藝條件：反應(yīng)溫度為111℃、丙酮用量為29%、反應(yīng)時間為3.5h,最高收率可達54.70%,較前人提高了9%。最后,采用732型陽離子交換樹脂對解蔽后的三甲基賴氨酸的反應(yīng)液分離純化。通過單因素實驗確定了吸附、解吸的最佳反應(yīng)條件：吸附時間為1.0h、吸附pH=5.0、溫度為25℃,初始解吸pH=10.0,洗脫劑為pH=10.8的稀氨水。并通過薄層色譜、熔點測定和紅外色譜對目標(biāo)產(chǎn)物進行了鑒定分析。
[Abstract]:Hypertension is the most common cardiovascular disease in the elderly. In recent years, due to learning, work, all aspects of diet, hypertension also appeared in the young crowd. Kelp (also known as brown algae) laminine contains a basic amino acid have lower blood pressure, blood lipid lowering effect. Good effect on prevention and treatment of hypertension and coronary heart disease and other cardiovascular diseases. At present, as a class of drugs of kelp ammonia acid, researches on it are rarely, commercially available laminine has yet to appear. Very little content of laminine in kelp, the extraction method of cost is too high and will cause a lot of waste, so it is not suitable for industrial production. This paper complies with the requirements of green chemistry, low toxicity to the "green" reagent dimethyl carbonate two as methylating reagent, preparation of laminine by total chemical synthesis, and response Analysis of the influence of various factors chelating reaction and methylation reaction surface method to optimize the preparation process of the two, the blood pressure lowering drug laminine clean production. First of all, this thesis adopts metal ion chelating protection alpha -NH2. lysine of Ca2+, Mg2+, Cu2+, Zn2+, Ni2+ five the metal ions respectively with lysine chelate reaction was determined for alpha -NH2 protection using Cu2+. Through single factor experiments, more important influencing factors as reaction temperature, time and pH system, and to determine the optimal process for the synthesis of Copper Lysine by response surface experiment: reaction temperature is 66 DEG C and the reaction time was 1.5h, pH value of Copper Lysine 7.5. to optimal solution synthesis of 80% ethanol solution after separation and purification, the yield is 93.15%. second, using two methyl carbonate prepared epsilon -N three methyl lysine as methylating reagent. Through single factor experiment and response The response surface experiments to explore the reaction temperature, time, catalyst, reaction system, the effect of phase transfer catalyst reaction of methyl, optimize the synthesis of -N three methyl lysine epsilon optimum conditions of acid ammonia: reaction temperature is 111 DEG C, amount of acetone was 29%, the reaction time is 3.5H, the highest yield of 54.70%, compared with the previous increase 9%. finally, the 732 type cation exchange resin of three methyl demasking after Lai reaction liquid acid ammonia separation and purification. The adsorption was determined by single factor experiment, the optimum reaction conditions were: adsorption time is 1.0h, the adsorption of pH=5.0, the temperature is 25 DEG C, the Initial Desorption of pH=10.0, eluent for dilute ammonia pH=10.8. And by TLC, determination of melting point and infrared spectrum analysis of the target product were identified.

【學(xué)位授予單位】：青島科技大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R914.5

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