【作者】 闫喜龙；

【导师】 冯亚青； 陈立功；

【作者基本信息】 天津大学 ， 应用化学， 2004， 博士

【摘要】 邻氨基醇类化合物是一类非常重要的化合物，随着人们对手性化合物的深入研究，手性邻氨基醇类化合物得到日益广泛地应用，本文对（S）-2-氨基丙醇和（S）-2-氨基丁醇及相关药物的合成进行了系统地研究。本文分别对（S）-2-氨基丙醇和左氟沙星的合成进行了研究，主要包括以下内容：以环氧丙烷为起始原料通过氨解开环、硫酸酯化成环和邻苯二甲酸酐开环制得外消旋的2-氨基丙醇；以硝基乙烷和甲醛为原料反应得到2－硝基丙醇再以骨架镍为催化剂，催化还原得到外消旋的2-氨基丙醇，收率为72.0％直接用硼氢化钠还原L-丙氨酸乙酯，并摸索出硼氢化钠还原的最佳工艺条件，（S）-（＋）-2-氨基丙醇的收率最高达84.7％。使用ZnCl2对硼氢化钾进行改性后，用于L-丙氨酸酯的还原，（S）-（＋）-2-氨基丙醇收率可达60.2％。采用金属钠和BER树脂还原L-丙氨酸乙酯，（S）-（＋）-2-氨基丙醇收率分别达到45.1％和32.6％。以2，3，4，5-四氟苯甲酸为起始原料合成左旋氧氟沙星，并对其工艺路线进行改进，总收率为14.1％，并合成了一系列左旋氧氟沙星的类似物，以用于生物活性评价。本文对抗结核药物盐酸乙胺丁醇的合成进行了系统地研究，包括原料（R，S）-2-氨基丁醇的合成、拆分，（R）-2-氨基丁醇的消旋以及L-(+)-酒石酸的回收。以1-丁烯、氯气和乙腈为原料，合成（R，S）-2-氨基丁醇，收率可达25%以上；选用L-(+)-酒石酸拆分（R，S）-2-氨基丁醇，得到酸式（S）-2-氨基丁醇的L-(+)-酒石酸盐，收率可达94%；滤液经处理后，得到酸式（R）-2-氨基丁醇的L-(+)-酒石酸盐晶体，收率可达99%；将得到的两种酸式2-氨基丁醇的L-(+)-酒石酸盐分别进行水解，得到（R）-2-氨基丁醇和（S）-2-氨基丁醇，总收率均达到85%；选用骨架镍催化剂，使（R）-2-氨基丁醇进行消旋化反应，收率可达70%<WP=3>以上，反应混合物无旋光；水解得到的酒石酸钠晶体用于L-(+)-酒石酸的回收，收率达70%以上。对以（S）-2-氨基丁醇和1,2-二氯乙烷为反应原料，合成产物乙胺丁醇的工艺路线进行了探讨，对不同的投料比，反应时间等工艺参数进行了优化，收率为81.25%。更多还原

【Abstract】 Vicinal amino alcohols are an important class of compounds . With the development of chiral compounds, chiral vicinal amino alcohols are widely . (S)-2-amino-1-propanol, (S)-2-amino-1-butanol and Related Pharmaceuticals were investigated in this paper. The synthesis of (S)-(+)-2-amino-1-propanol and Levofloxacin were investigated in this paper. The main work was described as following:(R,S)-2-amino-1-propanol was obtained from propylene oxide through treatment of propylene oxide with ammonia, esterification and cyclization with sulfuric acid and ring opening reaction with phthalic anhydride. Furthermore 2-amino-1-propanol was prepared in 72% yield from condensation of nitroethyane and formaldehyde, followed by hydrogenation with Raney Ni.(S)-(+)-2-amino-1-propanol was prepared in 84.7% yield by the reduction of ethyl L-alaninate with sodium borohydride, the reaction parameters were optimized.KBH4 was modified with ZnCl2, and employed as reducing agent for reduction of ethyl L-alaninate to afford (S)-(+)-2-amino-1-propanol in 60.2%.Sodium and BER resin were separately used to reduce ethyl L-alaninate to produce (S)-(+)-2-amino-1-propanol in 45.1% and 32.6% yield.Levofloxacin was synthesized in 14.1% total yield from 2,3,4,5-tetrafluoro-benzoic acid and the synthetic procedures were optimized. A series of derivatives of Levofloxacin were prepared for biological activities test.The synthesis of ethambutol hydrochloride used as an antituberculosis agent, was studied systematically in this paper, including the synthesis and resolution of (R,S)-2-aminobutanol, racemization of (R)-2-aminobutanol and the recovery of L-(+)-tartaric acid. The (R,S)-2-aminobutanol was synthesized from 1-butene, chlorine and <WP=5>acetonitrile in a yield of over 25%. The (S)-2-aminobutanol L-(+)-tartrate was obtained from the resolution of (R,S)-2-aminobutanol with L-(+)-tartaric acid in 94% yield, and (R)-2-aminobutanol L-(+)-tartrate was recovered in 99% yield by the treatment of the filtrate. The optically pure (S)-2-aminobutanol and (R)-2-aminobutanol were obtained over 85% yield by the hydrolysis of two 2-aminobutanol L-(+)-tartrate isomers separately. In the presence of racemization of (R)-2-aminobutanol proceeds effectively of Raney Ni to afford (R,S)-2-aminobutanol in a yield of over 70%. The mixtures have no optical rotation. The L-(+)-tartaric acid was recovered over 70% yield from sodium tartrate which was obtained through the hydrolysis of (R,S)-2-aminobutanol L-(+)-tartrate. What’s more, the synthesis of ethambutol from (S)-2-aminobutanol and 1,2-dichloroethane was investigated intensively. The process parameters, such as the ratio of starting materials and the reaction time, were optimized. Thus, the optically pure ethambutol was obtained in 81.25% yield under the optimum reaction conditions.更多还原