【摘要】：(一)3-芳基丁酸酯類化合物不對(duì)稱合成研究 1.通過(guò)對(duì)烯丙基砜的加成反應(yīng)高立體選擇性合成4-氟-3-芳基丁酸酯類化合物 本次研究發(fā)展了馬來(lái)酸半硫酯(MAHTs)與2-芳基取代的烯丙基砜脫羧加成反應(yīng),并取得很好的效果。通過(guò)調(diào)節(jié)催化劑的pKa值,設(shè)計(jì)一系列的催化模型,最終運(yùn)用以奎寧為基本骨架芐基取代的硫脲為催化劑催化該反應(yīng)。經(jīng)過(guò)對(duì)加成產(chǎn)物修飾最終合成一氟取代3-甲基茚酮和一氟取代姜黃酮等潛活性化合物。 2.通過(guò)對(duì)烯丙基砜的加成反應(yīng)高立體選擇性合成4-氟-2-羥基-2-烷基-3-芳基丁酸酯類化合物 本文發(fā)展了5H-惡唑-4-酮的邁克爾加成反應(yīng),高立體選擇性合成了4-氟-2-羥基-2烷基-3-芳基丁酸酯類化合物。該研究的難點(diǎn)在于運(yùn)用氫鍵誘導(dǎo)的烯丙基砜的加成反應(yīng),并且同時(shí)構(gòu)建兩個(gè)手性中心化合物；優(yōu)點(diǎn)在于催化劑用量較低(1-10mol%),處理簡(jiǎn)單(過(guò)濾),適用于工業(yè)化生產(chǎn)；意義在于合成具有藥物活性的含氟原子的α-羥基酸類、多羥基類、姜黃類等衍生物；證明存在非經(jīng)典氫鍵作用時(shí),反應(yīng)的立體選擇性會(huì)有效增強(qiáng)。 (二)含雜原子季碳中心化合物不對(duì)稱合成研究 1.有機(jī)催化5H-惡唑-4-酮與硝基烯烴的不對(duì)稱邁克爾加成 第一次用有機(jī)催化實(shí)現(xiàn)了5H-惡唑-4-酮和硝基烯烴的不對(duì)稱邁克爾加成反應(yīng)。運(yùn)用易于制備的L-叔亮氨酸衍生的叔胺硫脲雙官能團(tuán)催化劑催化得到高立體選擇性化合物,經(jīng)過(guò)一步簡(jiǎn)單水解得到α-羥基α-烷基酸的衍生物。 2.有機(jī)催化異惡唑類化合物的不對(duì)稱硫醚化 運(yùn)用金雞納生物堿衍生的叔胺環(huán)狀氨基化合物作為催化劑,4A分子篩作為添加劑,發(fā)展了第一例異惡唑類與N-(硫基)琥珀酰亞胺的不對(duì)稱硫醚化反應(yīng)。在此條件下4位烷基、芐基取代的異惡唑和N-(硫芐基、硫烷基、硫芳基)琥珀酰亞胺進(jìn)行不對(duì)稱硫醚化反應(yīng)獲得高立體選擇性的產(chǎn)物(81-95%ee)。 3.5H-惡唑-4-酮與N-(硫基)琥珀酰亞胺的不對(duì)稱硫醚化 運(yùn)用金雞納生物堿衍生的叔胺環(huán)狀氨基化合物作為催化劑,催化5H-惡唑-4-酮與N-(硫基)琥珀酰亞胺的不對(duì)稱硫醚化取得很好的進(jìn)展。這是第一例運(yùn)用不對(duì)稱催化手段構(gòu)建生物活性中間體α-羥基α-巰基酸類衍生物。
[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
【學(xué)位授予單位】：河南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5

【共引文獻(xiàn)】

相關(guān)期刊論文 前2條

1 王汝一;張姝;譚艷紅;洪偉耀;成波;陳慶鑫;朱蘊(yùn)韜;馮連順;;唾液酸衍生物的合成進(jìn)展[J];有機(jī)化學(xué);2014年03期

2 陳寶龍;鄧旭;曾光堯;郭虹;周應(yīng)軍;;神經(jīng)氨酸酶抑制劑抗流感病毒的研究進(jìn)展[J];中國(guó)藥學(xué)雜志;2015年01期

相關(guān)會(huì)議論文 前1條

1 王銳;;非天然氨基酸的手性合成及在多肽藥物研發(fā)中的應(yīng)用[A];2012年中國(guó)藥學(xué)大會(huì)暨第十二屆中國(guó)藥師周論文集[C];2012年

相關(guān)博士學(xué)位論文 前2條

1 耿志聰;有機(jī)小分子催化的一些Michael加成啟動(dòng)的不對(duì)稱串聯(lián)反應(yīng)研究[D];蘇州大學(xué);2014年

2 孟欣;雙唾液酸化四糖抗原表位的化學(xué)酶法合成研究[D];山東大學(xué);2014年

相關(guān)碩士學(xué)位論文 前2條

1 韓志強(qiáng);金雞納生物堿衍生物催化的硫醚化及Mannich反應(yīng)[D];河南大學(xué);2013年

2 范昊坤;5，5-二甲基乙內(nèi)酰脲二聚體的合成及晶體結(jié)構(gòu)[D];廣西大學(xué);2013年

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本文編號(hào)：2305049