本文選題：4 + 5-二取代-2-哌啶酮�。� 參考：《重慶大學(xué)》2014年碩士論文

【摘要】：手性4,5-二取代-2-哌啶酮化合物是一類C4、C5取代的含羰基的六元哌啶雜環(huán)化合物，其作為手性合成子不僅能夠合成多種具有藥理活性和生物活性的哌啶衍生物，同時(shí)還能通過化學(xué)轉(zhuǎn)化，制備多種藥用天然產(chǎn)物，如抗抑郁藥帕羅西丁，細(xì)胞毒性和鈣調(diào)素拮抗劑Pseudodistomin A、B，和降血壓藥物利血平等。另外手性4,5-二取代-2-哌啶酮由于結(jié)構(gòu)中含多個(gè)官能基，可以通過發(fā)生C2羰基還原、C3烯醇烷基化、C4芳基化、C5碳鏈延長(zhǎng)反應(yīng)等構(gòu)建更復(fù)雜的骨架，因而在合成上具有廣泛的應(yīng)用價(jià)值。 本論文以鄰苯二甲酰胺保護(hù)的化合物70為原料，運(yùn)用Evans教授發(fā)展的VA唑烷酮誘導(dǎo)的烯醇烷基化反應(yīng)引入C5位手性中心制備化合物72a；化合物72a經(jīng)7步反應(yīng)制備了醛107，并隨即與乙酸甲酯發(fā)生Aldol反應(yīng)延長(zhǎng)一個(gè)碳鏈形成化合物109；化合物109發(fā)生內(nèi)酰胺反應(yīng)分別以14步、22%和21%的總收率制備了4,5-二取代-2-哌啶酮1和2。中間體1和2通過硅膠柱進(jìn)行純化分離。經(jīng)手性柱分析1和2，我們發(fā)現(xiàn)其為消旋體，說明醛107在堿作用下α位極易消旋，造成化合物1和2的C5位發(fā)生消旋。在本論文中，我們也對(duì)消旋化的可能機(jī)理進(jìn)行了討論。
[Abstract]:Chiral 4o 5-disubstituted -2-piperidinone compounds are a class of C4C5-substituted hexagonal piperidine heterocyclic compounds. As chiral synthesizers, they can not only synthesize many kinds of piperidine derivatives with pharmacological and biological activities.At the same time, many kinds of medicinal natural products can be prepared by chemical transformation, such as paroxetine, cytotoxicity and calmodulin antagonist Pseudodistomin Afib, and antihypertensive drug reserpine.In addition, chiral 4o 5- disubstituted -2-piperidinone has many functional groups in its structure, so it can be used to form a more complex skeleton by C _ 2 carbonyl reductive C _ 3 enol alkylation, C _ 4 arylation of C _ 4 aromatization and C _ 5 C _ 5 chain prolongation.Therefore, it has wide application value in synthesis.In this paper, phthalamide protected compound 70 was used as raw material.The alkylation of enol induced by VA azolone developed by Professor Evans was introduced into the chiral center of C 5 to produce 72a, and compound 72a was prepared by 7 steps reaction, and then extended a carbon chain by Aldol reaction with methyl acetate.Compound 109 was synthesized by lactam reaction of compound 109 in the total yield of 14 steps 22% and 21% respectively to prepare 4o 5-disubstituted -2-piperidinone 1 and 2.Intermediates 1 and 2 were purified by silica gel column.By analyzing 1 and 2 by chiral column, we found that they are racemes, indicating that aldehydes 107 are easily racemic at the 偽 position under the action of alkali, which results in the racemization of C 5 of compounds 1 and 2.In this paper, we also discuss the possible mechanism of racemization.
【學(xué)位授予單位】：重慶大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 王澍;;營(yíng)造瑣記[J];世界建筑;2012年05期

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本文編號(hào)：1742782