本文選題：螺環(huán)化合物 + 硫葉立德�。� 參考：《成都學院》2017年碩士論文

【摘要】：螺環(huán)骨架是藥用化合物中非常重要的一類結構骨架。由于其高效的藥用價值,螺環(huán)骨架也一直是有機化學中的研究熱點。本文通過硫葉立德和BINOL手性磷酸,成功的合成了螺環(huán)環(huán)丙烷產(chǎn)物,和N-雜螺環(huán)產(chǎn)物,為螺環(huán)化合物的研究和發(fā)展提供了有力的參考借鑒。本文的第一章對環(huán)丙烷的研究進展進行了系統(tǒng)的綜述,包括環(huán)丙烷的理化特性、藥用價值、參與的主要化學反應和主要構建方法等。環(huán)丙烷對藥物體內(nèi)代謝的影響主要包括增加整體結構的穩(wěn)定、延緩化合物的氧化代謝,以及改變藥物的親脂性等。目前,多種含有環(huán)丙烷骨架的化合物已作為安全有效的藥物進入了臨床使用,包括抗癌藥物Lenvatinib,抗HCV藥物Boceprevir和Ledipasvir等。從結構上分析,環(huán)丙烷的C-C鍵與烯烴的C=C具有相類似的反應活性,在催化劑的作用下能夠發(fā)生開環(huán)反應,生成1,3-兩性離子中間體,進而與親核試劑或者親電試劑發(fā)生反應構建各類雜環(huán)體系。目前,已報道的環(huán)丙烷的構建方法主要是Simmons-Smith反應、過渡金屬催化的成環(huán)丙烷反應,以及Michael-initiated關環(huán)反應。本文的第二章報道了一種基于硫葉立德構建螺環(huán)環(huán)丙烷骨架的方法。該實驗以穩(wěn)定的硫葉立德和缺電子環(huán)烯酮為底物,合成了一系列螺環(huán)環(huán)丙烷產(chǎn)物。該實驗具有反應活性高、高產(chǎn)率和高非對映選擇性等優(yōu)勢,同時反應條件溫和,操作簡便。并且通過手性誘導的方式,合成了具有對映選擇性的螺環(huán)環(huán)丙烷產(chǎn)物,該手性系列產(chǎn)物的反應同樣具有高產(chǎn)率。本文的第三章論述了BINOL手性磷酸的合成及應用。對制備手性BINOL磷酸的工藝路線進行了簡單的優(yōu)化,得到了一條高效、簡便的合成路線。使用所制備的BINOL磷酸催化劑實現(xiàn)了缺電子環(huán)烯酮和吖內(nèi)酯衍生物的[2+3]成環(huán)反應,得到了系列N-雜五元螺環(huán)產(chǎn)物。該反應不但具有高產(chǎn)率,同時具有很高的立體選擇性。
[Abstract]:Snail cytoskeleton is one of the most important structural skeletons in medicinal compounds. Because of its efficient medicinal value, snail skeleton has been a hot spot in organic chemistry. In this paper, the products of spirocyclic propane and N-heterospira were successfully synthesized by using sulfurylide and BINOL chiral phosphoric acid, which provides a useful reference for the research and development of spirocyclic compounds. In the first chapter, the research progress of cyclopropane is reviewed systematically, including the physicochemical properties, medicinal value, main chemical reactions and construction methods of cyclopropane. The effects of cyclopropane on drug metabolism mainly include increasing the stability of the whole structure, delaying the oxidative metabolism of compounds, and changing the lipophilicity of the drug. At present, many kinds of compounds containing cypropane skeleton have been used as safe and effective drugs, including the anticancer drugs Lenvatinib, HCV drugs Boceprevir and Ledipasvir and so on. The structure analysis shows that the C-C bond of cyclopropane has a similar activity to that of alkenes, and the ring opening reaction can take place under the action of catalyst to form an intermediate of 1 ~ (3) -amphoteric ion. Furthermore, various heterocyclic systems were constructed by reaction with nucleophilic reagents or electrophilic reagents. At present, the construction methods of cyclopropane are mainly Simmons-Smith reaction, transition metal catalyzed cyclopropane reaction and Michael-initiated ring closing reaction. In the second chapter, a method of constructing the framework of spirocyclic propane based on Sulphur is reported. In this experiment, a series of spirocyclic propane products were synthesized by using stable ylide and electron-deficient cycloketene as substrates. The experiment has the advantages of high reaction activity, high yield and high enantioselectivity. The reaction conditions are mild and the operation is simple. The enantioselective products of spirocyclic propane were synthesized by chiral inducement. The reaction of the chiral series was also of high yield. In chapter 3, the synthesis and application of BINOL chiral phosphoric acid are discussed. A simple and simple synthetic route of chiral BINOL phosphoric acid was obtained. Using the prepared BINOL phosphoric acid catalyst, the [23] ring formation reaction of electron-deficient cyclienone and acridine derivatives was carried out, and a series of N-hetero-pentagonal spiroring products were obtained. This reaction not only has high yield, but also has high stereoselectivity.
【學位授予單位】：成都學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R914.5

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1 Jeerang Wongtrakul;Atchara Paemanee;Phitchayapak Wintachai;Chutima Thepparit;Sittiruk Roytrakul;Thananya Thongtan;Kanokwan Janphen;Khuanchai Supparatpinyo;Duncan R.Smith;;Nevirapine induces apoptosis in liver(HepG2) cells[J];Asian Pacific Journal of Tropical Medicine;2016年06期

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本文編號：1847534