肝素类寡糖合成研究进展

肝素(heparin,HP)和硫酸乙酰肝素(heparan sulfate,HS)是糖胺聚糖(glycosaminoglycans,GAGs)家族中的一类线性硫酸化多糖,其结构复杂、牛物活性多样.为了深入研究其结构序列与小同生物活性之间的关系,近年来针对肝素类寡糖的合成与功能研究成为糖化学和糖牛物学研究的一个热点领域,涌现出一些新的合成方法与合成策略.选取了2001年以来国际上一些在肝素类寡糖的化学合成和酶法合成方面的代表性工作予以综述.     

组合化学在功能材料合成方面的应用

组合化学方法是当今材料科学和化学领域的研究热点。组合化学方法首先在新药的合成领域得到应用, 很快就以其合成周期短、合成的样品数量大、节约经费等诸多优点而拓展到功能材料的合成等其它领域。组合化学的方法有许多种, 按照反应相的不同可以分为液相中的组合合成法和固相中的组合合成法, 固相组合合成又可以根据所选用的掩模方式的不同而分为二分阴影掩模法、四分阴影掩模法、可移动百叶窗式掩模法等几种, 可以根据材料合成的实际需求加以选择。     

无机功能材料的组合设计、制备和筛选

随着科学的不断发展和人类认识水平的提高,科学研究的手段必然要求高效和多能,研究的对象也日趋复杂和多样化,组合化学就是在这样的形势下发展起来的。组合化学最早被用于合成肽组合库,后来被用于药物的合成与筛选,也称组合合成,组合库和自动合成法。组合化学是一门集合成化学,组合数学和计算机辅助设计等多学科交叉形成的一门边缘学科。因此,组合化学可定义为利用组合论的思想和理论,将构建单元通过有机 /无机合成或化学法修饰,产生分子多样性的群体（库 ),并进行优化选择的科学。 组合化学从制药领域逐步发展到有机小分子 /高…     

寡糖的立体选择性合成策略

研究寡糖及缀合物的生物活性日益显现出重要的生物学意义, 采用化学合成方法研究特定的或糖苷键的构建对复杂寡糖及缀合物的合成极其重要. 到目前为止, 寡糖及其缀合物化学偶联立体选择性设计与合成策略是糖化学领域中十分活跃和引人注目的热点, 受到特别的关注. 综述了多年来高立体选择性寡糖的合成的研究进展.     

MALDI-TOF-MS用于组合化学肽库的鉴定

组合化学是一种快速制备大量相关化合物,并可快速对其进行生物活性筛选的革新性的技术和方法。组合化学法自问世以来在生命科学和医药科学技术等领域获得了飞速发展。组合化学肽库已成为同时制备大量不同序列多肽的方法,并已广泛用于抗原决定簇、生物分子相互作用、亲和抑制剂、新药筛选等研究。在亲和筛选研究中,合成组合肽库的评价以及结构鉴定是研究成败的关键步骤之一。     

几丁寡糖结构类似物的化学合成

合成了两个结构新颖的几丁寡糖结构类似物: β-1,3连接的乙酰氨基葡聚二糖和β-1,3连接的乙酰氨基葡聚三糖, 并通过核磁共振和质谱分析确证了其化学结构. 与天然的几丁寡糖不同, 本文所合成的葡聚二糖和葡聚三糖均采取了1→3糖苷键的连接方式, 为研究几丁寡糖诱导植物抗病活性与寡糖区域异构体之间的关系提供有用材料.     

阿拉伯、半乳和果呋喃寡糖的生物来源及合成进展

由呋喃型阿拉伯糖、半乳糖和果糖构成的寡糖及其糖缀合物广泛分布于自然界,主要存在于植物和低等生物,如细菌、原生动物、真菌,是细胞壁糖肽、糖脂和核苷酸糖类的重要组成部分,具有广泛的生物学意义,其合成和化学生物学研究一直备受关注.综述了近年这些呋喃寡糖的生物来源及合成研究进展.     

若干具有复杂结构的寡糖及其缀合物的合成

通过化学合成手段得到一定量的具有特殊活性的寡糖或其缀合物,及其改变结构的类似物不但有助于阐明糖基在生命过程中的作用,同时亦对有机合成化学提出了挑战,对生命科学和有机化学的发展都有很大的意义。我们实验室运用己有的和发展了的合成方法学对若干具有重要活性的复杂寡糖和中药活性成分的皂甙进行了合成,在这里报导了三个目标分子的工作结果。     

一种木葡聚糖类寡糖的化学合成及生物活性

天然木葡聚糖类寡糖是一类对植物生长具有调节作用的寡糖, 本文以3个单糖组分为原料, 经5步合成了一种木葡聚糖三糖(1)(总产率15%), 以及该三糖的糖苷缀合物1a及其异构体1b. 利用糖基化立体选择性原则, 一步偶联反应同时得到所需的α,β连接产物, 整个合成路线高效简捷. 活性测试结果表明, 3种目标寡糖在1 mg/L浓度下, 对烟草的生长均显示出一定的促进作用, 表明所合成的3种寡糖有望发展成为植物生长促进剂.     

催化不对称反应最新进展(Ⅱ)－组合化学方法之 应用

组合化学技术已经成为药物、新型固体材料和催化剂合成、评价和筛选的一种有力工具,最近它在催化不对称反应的手性催化剂高效率合成与筛选方面的应用也受到了重视,本文将综述组合化学技术在发展不对称合成新型催化剂方面的应用。第一部分主要介绍手性催化剂(或配体)库的固相平行合成;第二部分重点总结了所建立的手性催化剂库的高效率评价技术及其应用。     

Recent developments in oligosaccharide synthesis: tactics,solid-phase synthesis and library synthesis

Oligosaccharides, commonly found on the cell surfaces, are deeply involved in a variety of important biological functions, yet demanding difficulties synthesizing such structures limit the investigation of their functions. Technologies to chemically synthesize these oligosaccharides have dramatically advanced during the last two decades mainly due to the introduction of good anomeric leaving groups. In addition, tactical analyses have been addressed to enhance the overall efficiency of oligosaccharide synthesis. Based on the advancement of solution-phase chemistry, solid-phase technologies are being investigated in connection with the current trend of combinatorial chemistry and high throughput screening. This review summarizes the necessary solution-phase methodologies, the status of solid-phase synthesis of oligosaccharides, and combinatorial synthesis of oligosaccharide libraries.     

A Method of Orthogonal Oligosaccharide Synthesis Leading to a Combinatorial Library Based on Stationary Solid‐Phase Reaction

A new, efficient synthesis of oligosaccharides, which involves solid‐phase reactions without mixing in combination with an orthogonal‐glycosylation strategy, is described. Despite a great deal of biological interest, the combinatorial chemistry of oligosaccharides is an extremely difficult subject. The problems include 1) lengthy synthetic protocols required for the synthesis and 2) the variety of glycosylation conditions necessary for individual reactions. These issues were addressed and solved by using the orthogonal‐coupling protocol and the application of a temperature gradient to provide appropriate conditions for individual reactions. Furthermore, we succeeded in carrying out solid‐phase reactions with neither mechanical mixing nor flow. In this report, the synthesis of a series of trisaccharides, namely, α/β‐L ‐Fuc‐(1→6)‐α/β‐D ‐Gal‐(1→2/3/4/6)‐α/β‐D ‐Glc‐octyl, is reported to demonstrate the eligibility of the synthetic method in combinatorial chemistry.     

Glycopeptide and Oligosaccharide Libraries

Despite the burgeoning interest in the various biological functions and consequent therapeutic potential of the vast number of oligosaccharides found in nature on glycoproteins and cell surfaces, the development of combinatorial carbohydrate chemistry has not progressed as rapidly as expected. The reason for this imbalance is rooted in the difficulty of oligosaccharide assembly and analysis that renders synthesis a rather cumbersome endeavor. Parallel approaches that generate series of analogous compounds rather than real libraries have therefore typically been used. Since generally low affinity is obtained for interactions between carbohydrate receptors and modified oligosaccharides designed as mimetics of natural carbohydrate ligands, glycopeptides have been explored as alternative mimics. Glycopeptides have been proven in many cases to be superior ligands with higher affinity for a receptor than the natural carbohydrate ligand. High-affinity glycopeptide ligands have been found for several types of receptors including the E-, P-, and L-selectins, toxins, glycohydrolases, bacterial adhesins, and the mannose-6-phosphate receptor. Furthermore, the assembly of glycopeptides is considerably more facile than that of oligosaccharides and the process can be adapted to combinatorial synthesis with either glycosylated amino acid building blocks or by direct glycosylation of peptide templates. The application of the split and combine approach using ladder synthesis has allowed the generation of very large numbers of compounds which could be analyzed and screened for binding of receptors on solid phase. This powerful technique can be used generally for the identification and analysis of the complex interaction between the carbohydrates and their receptors.     

微波辅助组合合成的研究进展

微波辅助组合合成技术是近年来发展起来的一种新的制备化合物库的组合化学技术, 它不仅可以克服传统固相组合合成技术以及液相组合合成技术无法提高产物收率的不足, 而且利用该技术所制得的化合物库中对应的是高纯度的单一化合物, 采用高通量筛选技术可以快速直接地确定高活性结构, 极大地提高了新药开发的效率. 主要就近年来微波辅助组合合成技术的研究进展情况进行介绍, 内容包括固相组合合成、基于聚合物支载的催化剂的组合合成、液相组合合成、氟相组合合成以及组合平行合成等.     

液相组合合成研究进展

综述了近年来液相组合合成的研究进展,主要包括液相组合合成法(LPCS),氟合成,树状载体组合合成及高分子辅助试剂在液相组合合成中的应用等。     

Anomeric information obtained from a series of synthetic trisaccharides using energy resolved mass spectra

The majority of structural investigations of oligosaccharides based on mass spectrometry use naturally occurring oligosaccharides, which do not allow extracting any common feature associated with anomeric structures and linkage positions. In order to address the issue to find such characteristics possibly contained in oligosaccharide structure, a synthetic combinatorial trisaccharide library was analyzed. The trisaccharides used in the analysis consisted of L-fucose, D-galactose and D-glucose, in which individual glycosidic linkages existed in either alpha- or beta-anomers. The analysis of energy-resolved mass spectra (ERMS) and the scattered plot analysis of some parameters obtained from ERMS for a series of trisaccharides revealed that lower activation energy was required for the dissociation of alpha-glycosides of these sugars compared to those of the corresponding beta-anomers. It is suggested that this finding may be useful in structural analysis of natural oligosaccharides.     

Recent advances in liquid-phase combinatorial chemistry

In combination with high throughput screening, combinatorial organic synthesis of large numbers of pharmaceutically interesting compounds may revolutionize the drug discovery process. Although combinatorial organic synthesis on solid supports is a useful approach, several groups are focusing their research efforts on liquid-phase combinatorial synthesis by the use of soluble polymer supports to generate libraries. This macromolecular carrier, in contrast to an insoluble matrix, is soluble in most organic solvents and has a strong tendency for precipitation in particular solvents. Liquid-phase combinatorial synthesis is a unique approach since homogeneous reaction conditions can be applied, but product purification similar to the solid-phase method can be carried out by simple filtration and washing. This method combines the positive aspects of classical solution-phase chemistry and solid-phase synthesis. This review examines the recent applications (1995-1999) of soluble polymer supports in the synthesis of combinatorial libraries.     

Recent developments in the combinatorial synthesis of nitrogen heterocycles using solid phase technology

Recognizing the potential of combinatorial chemistry to accelerate drug discovery and development, most pharmaceutical and related industries are seriously looking toward combinatorial synthesis of compounds in order to facilitate the identification of 'lead' molecules. In particular, solid phase synthesis is the core technology for combinatorial chemistry and is widely used for generating libraries of structurally related compounds. Since many drugs contain the nitrogen heterocyclic component and since heterocycles possess a high order of structural diversity, a precise overview of recent progress in the combinatorial synthesis of nitrogen heterocycles using solid phase methodology would be useful. Since the progress in solid phase synthesis of organic molecules has been reviewed regularly from 1992 to 1998, only the development of solid phase combinatorial synthetic approaches of small nitrogen heterocycles since 1999 will be reviewed here. This review describes the solid phase synthesis of azepanes, benzodiazepines, benzimidazoles, benzothiazepines, cinnolines, indolizines, beta lactams, oxazepins, oxazoles including benzisooxazoles, hydantoins, piperidines, pyrimidines, pyrazolones, quinolones, trizolopyridazines and thiazoles.     

用不保护或少保护的糖基受体合成寡糖*

用不保护或少保护的葡萄糖、甘露糖、鼠李糖作为糖基受体,经由糖原酸酯的中间体,能高区选和立体选地合成寡糖. α-(1→6)-连接的甘露寡糖、β-(1→6)-连接的葡萄寡糖、3,6-支化的甘露寡糖及葡萄寡糖用此方法能用很简单步骤合成,如具有重要生物活性的寡糖植保素激活剂葡萄六糖、具有抗肿瘤活性的香菇多糖的活性片段,以及一些具有重要生理功能的多糖的重复单元等.本文同时简述了用少保护的半乳糖和氨基葡萄糖为糖基受体合成寡糖的进展.