【作者】 门宝琴；

【导师】 张征林； 邹建忠；

【作者基本信息】 东南大学 ， 应用化学， 2005， 硕士

【摘要】 氨基酸酯及其衍生物的合成是近年来迅速发展起来的一个新研究领域,它们在医药、化工、食品、农业等方面有着越来越广泛的应用,可用作药物中间体、食品添加剂、化妆品添加剂、矿物浮选剂和杀菌灭虫合剂等,应用前景十分广阔。研究开发工艺可靠、成本合理的氨基酸酯及其衍生物制备技术具有重要的理论和实际意义。本文研究了12种氨基酸酯的制备工艺,并对L-丝氨酸甲酯盐酸盐的合成作了较为系统的研究,继而分别以甘氨酸乙酯盐酸盐和L-丝氨酸甲酯盐酸盐为原料合成了N-苄基甘氨酸乙酯盐酸盐和环丝氨酸。对产品进行熔点、旋光度、IR、元素分析、1H-NMR和HPLC等表征和含量分析,确定合成产物即为目标产物,其主要质量指标已达到相关标准。以氨基酸为原料采用亚硫酰氯法制备了12种氨基酸甲(乙)酯盐酸盐,即L-丝氨酸甲酯盐酸盐、甘氨酸乙酯盐酸盐、甘氨酸甲酯盐酸盐、L-缬氨酸甲酯盐酸盐、L-苯丙氨酸乙酯盐酸盐、L-苯丙氨酸甲酯盐酸盐、L-酪氨酸乙酯盐酸盐、L-酪氨酸甲酯盐酸盐、L-精氨酸甲酯二盐酸盐、L-亮氨酸甲酯盐酸盐、L-蛋氨酸甲酯盐酸盐和L-丝氨酸乙酯盐酸盐等。对亚硫酰氯法制备L-丝氨酸甲酯盐酸盐的影响因素进行试验及优化,较佳工艺条件下酯化收率可达85.0%以上,产品含量≥98.0%。同时对NKC-9干氢树脂催化法制备L-丝氨酸甲酯盐酸盐的工艺进行试验及优化,较佳工艺条件下酯化收率可达62.0%以上,产品含量≥98.0%。初步分析比较了亚硫酰氯法和树脂催化法的工艺特点和发展趋势。以甘氨酸乙酯盐酸盐为原料制备了N-苄基甘氨酸乙酯盐酸盐。甘氨酸乙酯盐酸盐在碱性条件下与苄氯反应生成N-苄基甘氨酸乙酯,然后用HCl气体处理可得到N-苄基甘氨酸乙酯盐酸盐。通过研究物料配比、反应时间和反应温度对反应收率的影响,确定了较佳工艺条件,收率可达61.0%以上,产品含量≥99.0%。以L-丝氨酸甲酯盐酸盐为原料制备了环丝氨酸。L-丝氨酸甲酯盐酸盐和五氯化磷在氯仿溶剂中进行氯代反应生成2-氨基-3-氯丙氨酸甲酯盐酸盐,后者和羟胺在碱性溶液中发生环合反应得到环丝氨酸。分别对氯代和环合步骤的影响因素进行试验及优化,确定了较佳工艺条件,产品总收率可达46.7%以上,产品含量≥99.0%。为最终合成D-环丝氨酸研究奠定了基础。更多还原

【Abstract】 Amino acids esters and their derivatives, of which the synthesis has rapidly become a new research field in recent years, have been extensively used as medical semi-product, food additives, cosmetic additives, mineral flotation additives, germicides, etc. So research on the synthesis of amino acids esters and their derivatives are of great significance both in theoretical and in practical side.Preparation technologies of a series of amino acids esters were studied systematically, then the synthesis of N-benzyl glycine ethyl ester hydrochloride and cycloserine was also studied using glycine ethyl ester hydrochloride and L-serine methyl ester hydrochloride as raw material respectively in this paper. Final products were characterized by melting point determination, rotation determination, IR, element analysis, 1H-NMR and HPLC and their main qualities correspond to the related standards.Esterification of amino acids using thionyl chloride affords twelve amino acids esters hydrochloride, such as L-serine methyl ester hydrochloride, glycine ethyl ester hydrochloride, L-valine methyl ester hydrochloride, L-phenylalanine ethyl ester hydrochloride, L-tyrosine ethyl ester hydrochloride, etc. The influentical factors on the synthesis of L-serine methyl ester hydrochloride with thionyl chloride were studied and optimized. The final yield was up to 85.0% and puritiy was more than 98.0%. The other synthesis technology, esterification of L-serine using strong acid resin as catalyst was studied as well. In the optimum reaction condition, the yield was up to 62.0% and puritiy was more than 98.0%. Theses two technologies were analyzed and summarized.N-benzyl glycine ethyl ester hydrochloride was prepared from glycine ethyl ester hydrochloride. Glycine ethyl ester hydrochloride reacted with benzyl chloride to give N-benzyl glycine ethyl ester in the presence of alkali, which then was treated with hydrochloric gas to afford N-benzyl glycine ethyl ester hydrochloride. The effects of stuff molar ratio, reaction time and tempreture on the yield were studied. The final yield was up to 61.0% and purity was more than 99.0%.Cycloserine was produced using L-serine methyl ester hydrochloride as raw material. L-serine methyl ester hydrochloride was chloridized with phosphorus pentachloride to afford 2-amino-3-chloride propanic acid methyl ester hydrochloride, which was cyclized with hydroxylamine in the presence of alkali to give cycloserine. The conditions of chlorination and cyclization were optimized in each step of reaction. The total yield of cycloserine was 46.7% and purity was more than 99.0%. The route laid an elementary foundation for the study of D-cycloserine synthesis.更多还原