芳基丁酸酯类及杂季碳化合物不对称合成研究
发布时间：2018-11-01 20:43
【摘要】：(一)3-芳基丁酸酯类化合物不对称合成研究 1.通过对烯丙基砜的加成反应高立体选择性合成4-氟-3-芳基丁酸酯类化合物 本次研究发展了马来酸半硫酯(MAHTs)与2-芳基取代的烯丙基砜脱羧加成反应,并取得很好的效果。通过调节催化剂的pKa值,设计一系列的催化模型,最终运用以奎宁为基本骨架苄基取代的硫脲为催化剂催化该反应。经过对加成产物修饰最终合成一氟取代3-甲基茚酮和一氟取代姜黄酮等潜活性化合物。 2.通过对烯丙基砜的加成反应高立体选择性合成4-氟-2-羟基-2-烷基-3-芳基丁酸酯类化合物 本文发展了5H-恶唑-4-酮的迈克尔加成反应,高立体选择性合成了4-氟-2-羟基-2烷基-3-芳基丁酸酯类化合物。该研究的难点在于运用氢键诱导的烯丙基砜的加成反应,并且同时构建两个手性中心化合物；优点在于催化剂用量较低(1-10mol%),处理简单(过滤),适用于工业化生产；意义在于合成具有药物活性的含氟原子的α-羟基酸类、多羟基类、姜黄类等衍生物；证明存在非经典氢键作用时,反应的立体选择性会有效增强。 (二)含杂原子季碳中心化合物不对称合成研究 1.有机催化5H-恶唑-4-酮与硝基烯烃的不对称迈克尔加成 第一次用有机催化实现了5H-恶唑-4-酮和硝基烯烃的不对称迈克尔加成反应。运用易于制备的L-叔亮氨酸衍生的叔胺硫脲双官能团催化剂催化得到高立体选择性化合物,经过一步简单水解得到α-羟基α-烷基酸的衍生物。 2.有机催化异恶唑类化合物的不对称硫醚化 运用金鸡纳生物碱衍生的叔胺环状氨基化合物作为催化剂,4A分子筛作为添加剂,发展了第一例异恶唑类与N-(硫基)琥珀酰亚胺的不对称硫醚化反应。在此条件下4位烷基、苄基取代的异恶唑和N-(硫苄基、硫烷基、硫芳基)琥珀酰亚胺进行不对称硫醚化反应获得高立体选择性的产物(81-95%ee)。 3.5H-恶唑-4-酮与N-(硫基)琥珀酰亚胺的不对称硫醚化 运用金鸡纳生物碱衍生的叔胺环状氨基化合物作为催化剂,催化5H-恶唑-4-酮与N-(硫基)琥珀酰亚胺的不对称硫醚化取得很好的进展。这是第一例运用不对称催化手段构建生物活性中间体α-羟基α-巯基酸类衍生物。
[Abstract]:Study on Asymmetric Synthesis of (1) 3-arylbutyric Acid Ester 1. Synthesis of 4-fluoro-3-arylbutyric acid ester by stereoselective addition of allyl alcohol The study of compounds has developed the substitution of half-sulfur maleate (MAHTs) with 2-aryl. Allyl Methylene Addition Addition Reaction and Obtained A series of catalytic models are designed by adjusting the pka value of the catalyst, The reaction is catalyzed, and the addition product is modified to finally synthesize a fluorine substituted 3-methylpropone and a fluorine substituted curcumin and the like. synthesizing 4-fluoro-2-hydroxy-2-alkyl-3-In this paper, the aryl butyrate ester compound has been developed in this paper. Michael addition reaction of 4-ketone, high stereoselectivity synthesis of 4-fluoro-2-hydroxy-2-alkyl-3-arylbutyric acid ester compound. The difficulty in this study is to use hydrogen bond-induced addition reaction of allyl alcohol and simultaneously construct two chiral center compounds; the advantage is that the dosage of catalyst is low (1-10mol%), and the treatment is simple (too high). The method is suitable for industrial production; the invention is applicable to industrial production; the invention is characterized in that the derivative of the hydroxyl-hydroxy acid, the polyhydroxy compound, the curcumin and the like of the fluorine-containing atom with the medicinal activity is synthesized; and when the non-classical hydrogen bond is proved, the reaction The stereoselectivity can be effectively enhanced. Study on Asymmetric Synthesis of Sub-season Carbon Center Compounds 1. Organic Catalysis 5H-Malformation The asymmetric Michael addition of 4-one and nitroalkene has been achieved with organic catalysis for the first time. Asymmetric Michael addition reactions of 4-ketones and nitroolefins. A high stereoselectivity compound is obtained by using a readily prepared L-tert-leucine-derived tertiary amine or bis-functional catalyst to obtain a high stereoselectivity compound, Step simple hydrolysis to obtain derivatives of poly-hydroxy-2-alkyl-acid. 2. The asymmetric thioetherification of the organic catalytic isoenzymes compounds uses a tertiary amine cyclic amino compound derived from a gold chicken alkaloid as a catalyst, 4A molecular sieve as an additive, Asymmetric thioetherification of n-(thio) amber disulfides in a case of iso-evil pentanone and N-(thio) amber, under this condition, 4-bit alkyl, di-substituted isomyl and N-(thioalkyl, sulfur-alkyl, sulfur-aryl) amber are not symmetrical The thioetherification reaction yields a highly stereoselective product (81-95% ee). 3. 5H-Malformation-4-Ketone and N-(thio) Amber It is known that thioetherification utilizes a tertiary amine cyclic amino compound derived from a gold chicken alkaloid as a catalyst to catalyze 5H-The asymmetric thioetherification of p-4-one and N-(thio) amber is very good. This is the first
【学位授予单位】：河南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
本文编号：2305049
[Abstract]:Study on Asymmetric Synthesis of (1) 3-arylbutyric Acid Ester 1. Synthesis of 4-fluoro-3-arylbutyric acid ester by stereoselective addition of allyl alcohol The study of compounds has developed the substitution of half-sulfur maleate (MAHTs) with 2-aryl. Allyl Methylene Addition Addition Reaction and Obtained A series of catalytic models are designed by adjusting the pka value of the catalyst, The reaction is catalyzed, and the addition product is modified to finally synthesize a fluorine substituted 3-methylpropone and a fluorine substituted curcumin and the like. synthesizing 4-fluoro-2-hydroxy-2-alkyl-3-In this paper, the aryl butyrate ester compound has been developed in this paper. Michael addition reaction of 4-ketone, high stereoselectivity synthesis of 4-fluoro-2-hydroxy-2-alkyl-3-arylbutyric acid ester compound. The difficulty in this study is to use hydrogen bond-induced addition reaction of allyl alcohol and simultaneously construct two chiral center compounds; the advantage is that the dosage of catalyst is low (1-10mol%), and the treatment is simple (too high). The method is suitable for industrial production; the invention is applicable to industrial production; the invention is characterized in that the derivative of the hydroxyl-hydroxy acid, the polyhydroxy compound, the curcumin and the like of the fluorine-containing atom with the medicinal activity is synthesized; and when the non-classical hydrogen bond is proved, the reaction The stereoselectivity can be effectively enhanced. Study on Asymmetric Synthesis of Sub-season Carbon Center Compounds 1. Organic Catalysis 5H-Malformation The asymmetric Michael addition of 4-one and nitroalkene has been achieved with organic catalysis for the first time. Asymmetric Michael addition reactions of 4-ketones and nitroolefins. A high stereoselectivity compound is obtained by using a readily prepared L-tert-leucine-derived tertiary amine or bis-functional catalyst to obtain a high stereoselectivity compound, Step simple hydrolysis to obtain derivatives of poly-hydroxy-2-alkyl-acid. 2. The asymmetric thioetherification of the organic catalytic isoenzymes compounds uses a tertiary amine cyclic amino compound derived from a gold chicken alkaloid as a catalyst, 4A molecular sieve as an additive, Asymmetric thioetherification of n-(thio) amber disulfides in a case of iso-evil pentanone and N-(thio) amber, under this condition, 4-bit alkyl, di-substituted isomyl and N-(thioalkyl, sulfur-alkyl, sulfur-aryl) amber are not symmetrical The thioetherification reaction yields a highly stereoselective product (81-95% ee). 3. 5H-Malformation-4-Ketone and N-(thio) Amber It is known that thioetherification utilizes a tertiary amine cyclic amino compound derived from a gold chicken alkaloid as a catalyst to catalyze 5H-The asymmetric thioetherification of p-4-one and N-(thio) amber is very good. This is the first
【学位授予单位】：河南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5
【共引文献】
相关期刊论文 前2条
1 王汝一;张姝;谭艳红;洪伟耀;成波;陈庆鑫;朱蕴韬;冯连顺;;唾液酸衍生物的合成进展[J];有机化学;2014年03期
2 陈宝龙;邓旭;曾光尧;郭虹;周应军;;神经氨酸酶抑制剂抗流感病毒的研究进展[J];中国药学杂志;2015年01期
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1 王锐;;非天然氨基酸的手性合成及在多肽药物研发中的应用[A];2012年中国药学大会暨第十二届中国药师周论文集[C];2012年
相关博士学位论文 前2条
1 耿志聪;有机小分子催化的一些Michael加成启动的不对称串联反应研究[D];苏州大学;2014年
2 孟欣;双唾液酸化四糖抗原表位的化学酶法合成研究[D];山东大学;2014年
相关硕士学位论文 前2条
1 韩志强;金鸡纳生物碱衍生物催化的硫醚化及Mannich反应[D];河南大学;2013年
2 范昊坤;5，5-二甲基乙内酰脲二聚体的合成及晶体结构[D];广西大学;2013年
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