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题名: 几种活性寡糖及其衍生物和内酯类天然产物的合成与方法学研究
作者: 蔡超
学位类别: 博士
答辩日期: 2010
授予单位: 中国科学院研究生院
授予地点: 北京
导师: 杜宇国
关键词: 肝素 ; 寡糖合成 ; 硫酸皮肤素 ; (-)-Cleistenolide
中文摘要:       本文主要涉及到四个方面内容:综述了肝素类化合物的结构、活性、制备及化学修饰,天然产物MMP的全合成及糖脂间相互作用研究,硫酸皮肤素系列衍生物的合成,不饱和内酯类天然产物(-)-Cleistenolide的全合成研究。全文共分四章: 第一章 综述了近年来肝素类化合物的结构、活性、制备及化学修饰。 第二章 本章利用甘露糖施密特试剂作为供体,在TMSOTf催化下与硫苷受体进行高产率的偶联反应,经“4+4+4”的合成策略成功得到了MMP的十二糖及其半分子化合物,并对MMP与脂肪酸的相互作用做了质谱及SPR(表面等离子共振仪)研究,得到了其分子量相加的质谱图及MMP与长链脂肪酸作用的结合常数2.3×103 M-1。 第三章 本章设计合成了L-艾杜糖构型的糖醛酸,并对其官能团进行修饰后得到了三氯乙酰亚胺酯供体,通过X-ray衍射验证了其绝对构型,然后与氨基半乳糖受体反应得到肝素二糖。二糖既可作供体又可作为受体,偶联后变得到了硫酸皮肤素的四糖片断。硫酸皮肤素系列化合物的进一步修饰主要包括下面两个方面:(一)硫酸皮肤素二糖中的自由羟基硫酸酯化完成后,通过碱性条件下脱保护及鼓入氧气形成硫硫键,最后在加入氯酸金后硼氢化钠还原便得到了硫酸皮肤素二糖的纳米粒子。(二)以艾杜糖醛酸三氯乙酰亚胺酯和三氯乙氧甲酰基保护的氨基半乳糖硫苷为原料合成了含有叠氮基的硫酸皮肤素二糖及四糖片断,并以Cu(I)催化的1, 3-偶极环加成反应为基础构建了此单体的三价簇合物。 第四章 本章利用D-阿拉伯糖为手性模板,经过Wittig成稀反应,立体选择性1,3-反式异丙叉化反应,修饰后的Yamaguchi酯化反应等关键步骤,总共八步反应且总产率49%完成了对(-)-Cleistenolide的全合成工作。
英文摘要:       This dissertation is focusing on four part: The recent advances of structure, biological activity, preparation and chemical modification of Heparin. Total synthesis of MMP (3-O-methylmannose-containing polysaccharides) and the investigation of interaction between carbohydrate and fatty acid. Synthesis of dermatan sulfate derivatives. Total synthesis of (-)-Cleistenolide as natural unsaturated lactone. Four chapters are included as follows: In Chaper one, the recent advances of structure, biological activity, preparation and chemical modification of Heparin oligosaccharides were reviewed. In Chaper two, we describe that the mannose trichloroacetimidate as donor was coupled with acceptor in high yield using TMSOTf as catalyst. Though “4+4+4” synthetic strategy, we synthesize the dodeca- and hexasaccharide of MMP successfully. Then we investigated the interaction between carbohydrate and fatty acid using MS and SPR (Surface Plasmon Resonance). We got the molecular weight sum of MMP and fatty acid in mass spectrum, and the binding constant 2.3×103 M-1. In Chaper three, we designed and synthesized the sugar of L-iduronic acid, and it’s functional groups have been modified to achieve the trichloroacetimidate donor, which absolute configuration was verified by X-ray diffraction. With the coupling reaction of galactosamine acceptor, heparin disaccharide was obtained, and the disaccharide can be changed into donor or acceptor, then tetrasaccharide was achieved by coupling reaction.(i) the free hydroxyls of Dermatan Sulfate disaccharides were sulfated, and acyls were deprotected under basic conditions and oxygen was drumed into the solution to form sulfur-sulfur bond. After adding the Chloroauric acid, heparin disaccharide was attached to the nanoparticles by reduction of sodium borohydride. (ii) Dermatan sulfate di and tetrasaccharides containing azido group were prepared based on idopyranosiduronate trichloroacetimidate and Troc-protected galactosamine thioglycoside. Its trimer was also synthesized by using Cu(I) catalyzed 1, 3-dipolar cycloaddition reaction. In Chaper four, a facile stereoselective total synthesis of cleistenolide from natural chiral template D-arabinose has been achieved in eight steps and 49% overall yield, employing key steps including, Wittig olefination, selective 1,3-trans-acetal formation, and modified Yamaguchi esterification.
内容类型: 学位论文
URI标识: http://ir.rcees.ac.cn/handle/311016/35033
Appears in Collections:环境化学与生态毒理学国家重点实验室_学位论文

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Recommended Citation:
蔡超. 几种活性寡糖及其衍生物和内酯类天然产物的合成与方法学研究[D]. 北京. 中国科学院研究生院. 2010.
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