本文選題：甾體 + 甾體生物堿��； 參考：《貴州師范大學(xué)》2017年碩士論文

【摘要】：甾體是天然產(chǎn)物中一類重要化合物,具有多種生理活性,是重要的藥物分子或藥物原料。對具有活性的天然甾體分子進(jìn)行合成和結(jié)構(gòu)修飾,是開展甾體天然產(chǎn)物化學(xué)研究的重要工作。本論文開展了對幾個(gè)天然甾體分子的合成與結(jié)構(gòu)修飾,包含以下兩部分:(1)茄啶solanidine的合成:茄啶是一種結(jié)構(gòu)獨(dú)特的甾體生物堿,具有多種生物活性。田偉生課題組曾以薯蕷皂甙元為原料,采用Schmidt重排為關(guān)鍵反應(yīng)完成茄啶的合成。但在合成中出現(xiàn)了嚴(yán)重的C-25異構(gòu)化問題。本論文中,通過調(diào)整合成路線解決了異構(gòu)化反應(yīng)問題,并以發(fā)散式的方式完成茄啶和22-epi-茄啶兩個(gè)天然產(chǎn)物的合成。從薯蕷皂甙元醋酸酯出發(fā),經(jīng)開環(huán)置換的方式打開E環(huán)、C-25異構(gòu)化、選擇性內(nèi)酯接力還原、Schmidt重排/氮烷基化/立體選擇性亞胺鹽還原等九步反應(yīng),以24%總收率合成了茄啶。按類似的路線,在內(nèi)酯接力還原后,通過兩次分子內(nèi)氮烷基化反應(yīng)等共九步反應(yīng),17%的總收率完成22-epi-茄啶的合成。(2)甾體-托吡酯綴合物的合成:托吡酯為一種新型的抗癲癇藥,進(jìn)入臨床一線用藥品種,而青陽參總苷可以與苯妥英鈉共用臨床,其活性成分是C21甾體酯糖苷�；谇嚓枀⒖傑罩腥パ跆墙M成的糖鏈部分與托吡酯的糖衍生物(糖中羥基部分被低極性基團(tuán)覆蓋)的結(jié)構(gòu)特征,擬以托吡酯代替青陽參糖苷中的糖鏈部分,通過結(jié)構(gòu)修飾合成甾體-托吡酯綴合物,并同時(shí)模擬托吡酯活性基團(tuán)磺酰胺基,在甾體的C-3位置引入磺酰胺基。以青陽參C21甾體苷元告達(dá)庭和與其結(jié)構(gòu)類似而易得的C27甾體苷元及孕甾烷醇作為甾體部分,對其結(jié)構(gòu)改造和修飾,合成得到12個(gè)甾體新分子,其中包括了6個(gè)甾體-托吡酯綴合物和6個(gè)甾體氨基磺酸酯。
[Abstract]:Steroids are a kind of important compounds in natural products. They have many physiological activities and are important drug molecules or raw materials. The synthesis and structural modification of active natural steroids is an important work in the chemical research of steroids natural products. In this paper, the synthesis and structural modification of several natural steroids, including the following two parts: 1) Solanidine solanidine: Solanidine is a structurally unique steroidal alkaloid with a variety of biological activities. Tian Weisheng group used diosgenin as raw material and Schmidt rearrangement as the key reaction to complete the synthesis of solanidine. However, there is a serious problem of C-25 isomerization in the synthesis. In this paper, the isomerization reaction was solved by adjusting the synthesis route, and the synthesis of two natural products, Solanidine and 22-epi-solanidine, was completed in a divergent manner. Starting from diosgenin acetate and opening E-ring C-25 isomerization by ring-opening replacement, Solanidine was synthesized in 24% overall yield by selective lactone relay reduction, Schmidt rearrangement / nitroalkylation / stereoselective imine reduction. In a similar route, after lactone reduction, a total yield of 17% was obtained through two intramolecular nitrogen-alkylation reactions to complete the synthesis of 22-epi-solanidine steroid-topiramate conjugate: topiramate is a new antiepileptic drug. It can be shared with phenytoin sodium and its active component is C21 steroidal glucoside. Based on the structural characteristics of the sugar chain part of the total glucoside and the sugar derivative of topiramate (the hydroxyl group of the sugar is covered by the low polar group), topiramate is proposed to replace the sugar chain part of the glucoside. The steroid-topiramate conjugate was synthesized by structural modification, and the sulfonamide group of topiramate active group was simulated, and the sulfonamide group was introduced into the steroid C-3 position. Twelve steroidal new molecules were synthesized by modifying and modifying the steroidal glycosides of C21, C27 steroidal glycosides and pregnancy sterol, which are similar to the C21 steroidal glycosides. These include 6 steroidal-topiramate conjugates and 6 steroidal aminosulfonates.
【學(xué)位授予單位】：貴州師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O629.2

【參考文獻(xiàn)】

相關(guān)期刊論文 前7條

1 田偉生;史勇;;資源化學(xué)研究進(jìn)展[J];化學(xué)進(jìn)展;2010年04期

2 吳立文;呂瑞娟;;癲癇的藥物治療[J];中國神經(jīng)免疫學(xué)和神經(jīng)病學(xué)雜志;2010年02期

3 陳陽美,曾可斌,謝運(yùn)蘭,胡長林;青陽參對點(diǎn)燃癲癇大鼠腦內(nèi)c-fos、c-jun基因表達(dá)的影響[J];中藥藥理與臨床;2003年05期

4 章蘊(yùn)毅,王錦平,李佩芬,陳濱凌,李端,袁厚亮;黃楊寧改進(jìn)片增加動(dòng)物冠脈流量和抗心律失常作用[J];中國臨床藥學(xué)雜志;2001年05期

5 徐美娟;管致和;;番茄植株中生物堿類對菜青蟲(Pieris rapae L.)活性組分的分離和提純[J];北京農(nóng)業(yè)大學(xué)學(xué)報(bào);1994年02期

6 裴印權(quán),曹龍光,謝淑娟,蔡志基,木全章;青羊參的中樞藥理作用研究[J];北京醫(yī)學(xué)院學(xué)報(bào);1981年03期

7 匡培根;吳義新;孟繁瑾;匡培梓;邵道生;木全章;;青陽參治療癲癇大發(fā)作——附動(dòng)物實(shí)驗(yàn)觀察[J];中醫(yī)雜志;1980年08期

相關(guān)博士學(xué)位論文 前1條

1 李盛鈺;甾體皂苷糖鏈結(jié)構(gòu)修飾及抗腫瘤構(gòu)效關(guān)系研究[D];東北師范大學(xué);2007年

，

本文編號(hào)：1843762