点击化学及其应用

点击化学反应选用易得原料,通过可靠、高效化学反应快速合成大量新化合物,且反应条件温和、产物收率高和不需要专门的分离提纯。本文介绍了点击化学（click chemistry）的一些基本概念,综述了点击化学作为一种新的合成方法在药物中的先导化合物库、糖类化合物、天然化合物、生物大分子和高分子中聚合物上的应用,并对其发展前景进行了展望。     

Relationships between the Chemistry of Dispersed Metals and Chemical Syntheses with Metal Atoms

An interesting and topical question in modern inorganic chemistry is: To what extent are the well-known chemistry of dispersed metals and the new technique of chemical synthesis with free metal atoms interrelated? Or in other words: Where, do these two facets of metal chemistry meet? In an attempt to glean an answer to this question three important aspects are considered: metal sols, activated metals as powders, and deposits in vacuum processes (evaporation and cathodic sputtering of metals).     

Organometallic Syntheses with Diazoalkanes

In recent years, aliphatic diazo compounds have proved to be more and more versatile as reagents in the preparative chemistry of organometallic complexes. As readily accessible compounds, they are not only suitable for the synthesis of known kinds of metal complexes but also open fresh routes to novel complex systems. The comparatively new field of diazoalkane complex chemistry exhibits numerous unexpected and novel reactions, and introduces interesting and promising aspects into the chemistry of carbonylmetal compounds.     

分子识别指导下的有机分子设计、合成和组装——世纪交替时代的有机化学

在21世纪即将来临之际,有机化学将面临生命科学、环境科学和材料科学越来越多的挑战。本文回顾了在分子识别指导下的有机分子的设计、合成和组装这个新领域的诞生和发展,认为这个领域将成为新世纪有机化学发展的一个重要方向。它的发展和应用不仅使得有机化学可能较好地面对新挑战,同时能推动有机合成化学自身的发展。     

硫醇-烯/炔点击化学合成功能聚合物材料

点击化学具有反应条件温和、产率高、速率快、产物容易分离以及高度选择性等优点,成为国内外研究的热点之一。硫醇-烯/炔光化学反应作为新型高效的点击反应近年来备受关注,通过这种方法制备高性能及功能性聚合物材料也是新材料领域的前沿研究内容。本文综述了近年来硫醇-烯/炔点击化学在功能聚合物材料合成中的研究成果,详细介绍了硫醇-烯/炔点击化学的特点、优势及其反应机理,重点归纳了利用硫醇-烯/炔点击化学合成线型、超支化、交联等分子结构的功能聚合物材料的研究进展,并对由这种方法合成功能聚合物的单体特点、反应路线及产物应用进行了阐述,最后对硫醇-烯/炔点击化学的进一步应用前景做了展望。     

Green chemistry: state of the art through an analysis of the literature

Abstract

The literature of green chemistry has undergone a dramatic increase in the new millennium. Besides that, in ad hoc journals, papers of this type are published in journals of general, organic, and catalytic chemistry. The high proportion of communications within this area indicates that this is a hot topic. These reports mainly concern more environment-friendly synthetic methods, based on better catalytic systems, less harmful solvents and, more rarely, “alternative” physical techniques. Although the compliance with the green chemistry postulates is still partial, a trend in this direction is recognizable. For example, the number of preparative papers that introduce an environmental assessment is rapidly increasing.     

有机化学知识在高分子材料合成创新实验中的运用——分享几个实例

针对目前教学中存在的理论课程之间、实验课程与理论课程之间关联不够紧密等问题,探索了通过"知识关联"将有机化学基本知识运用到高分子材料合成创新实验中的教学思路。以新试剂合成及应用、荧光聚酯合成、聚酰胺合成、聚酯水解等为例,介绍了如何将有机化学新理论、新方法、新试剂应用于本科高分子化学和高分子材料实验教学,以及如何将有机化学的理论知识和实验手段应用于高分子材料合成教学中。实践表明:通过"知识关联",将有机化学基础理论知识和实验技能应用于高分子合成实验中可以提高学生对所学知识的理解和运用能力,增强学生的实验探索兴趣,有效改进了高分子材料合成实验教学的课堂气氛。     

Organocatalytic Asymmetric Synthesis of Organophosphorus Compounds

240 Years have passed since the discovery of elemental phosphorus. During that time organophosphorus chemistry has emerged as an interesting and exciting field of research. Recently organophosphorus chemistry has been raised to a new level. Organophosphorus compounds have found applications in asymmetric organocatalysis for the synthesis of optically active compounds of synthetic or biological importance. The aim of this review article is to present recent contributions to this developing field of chemistry and to point out synthetic advantages of methodologies developed so far.     

Metalloenzyme-Mediated Thiol-Yne Addition Towards Photoisomerizable Fluorescent Dyes

Proteins are able to irreversibly assemble biologically active ligands from building blocks bearing complementary reactive functions due their spatial proximity, through a kinetic target-guided synthetic process (also named in situ click chemistry). Although linkages thus formed are mostly passive, some of them have shown to significantly contribute to the protein binding through for instance hydrogen bonding and stacking interactions. Biocompatible reactions and click chemistry are a formidable source of inspiration for developing such new protein-directed ligations. This study reports a proximity-induced thiol-yne synthesis of carbonic anhydrase inhibitors. Not only this example widens the arsenal of kinetic target-guided synthesis (KTGS) eligible reactions, but the obtained product displayed unsuspected photophysical properties. The corresponding vinyl sulfide linkage conjugated to a coumarin core proved to be engaged in a monodirectional Z to E photoisomerization process. Further investigations guided by theoretical calculations showed that fine-tuning of the nature of the substituents on the coumarin moiety allows to obtain a bidirectional photochemical process, thus discovering a new photoswitching moiety, displaying moreover fluorescence properties. Due to the spectral tunability of coumarin derivatives, this work should open new opportunities for the design of vinyl sulfide-based photoswitch systems with modular photophysical properties.     

Synthetic Strategies for Constructing Two‐Dimensional Metal‐Organic Layers (MOLs): A Tutorial Review

Two‐dimensional (2D) metal‐organic layers (MOLs) are the 2D version of metal‐organic frameworks (MOFs) with nanometer thickness in one dimension. MOLs are also known as 2D‐MOFs, 2D coordination polymers, ultrathin MOF nanosheets (UMOFNs) or coordination nanosheets in literature. This new category of 2D materials has attracted a lot of interests because of the opportunity in combining molecular chemistry, surface/interface chemistry and material chemistry of low dimensional materials in these systems. Several synthetic strategies have been developed for the construction of 2D MOLs, but the general synthesis of MOLs still presents a challenge. This tutorial level review summarizes the recent progress in the fabrication of novel 2D MOLs and aims to highlight challenges in this field.     

Nitrogen-Containing Six-Membered Heterocycles: Solid-Phase Synthesis

Solid-phase organic synthesis is a rapidly expanding area of synthetic chemistry that is being widely exploited in the search for new medicinally important compounds using combinatorial techniques. In recent decades, a large number of reports related to solid-phase synthesis of heterocycles have appeared because of the wide variety of their biological activity. In this review, we report the important role of solid-phase synthesis in the synthesis of nitrogen containing six-membered ring heterocycles.     

Solid-Phase Synthetic Approach Toward the Synthesis of Oxygen-Containing Heterocycles

Solid-phase organic synthesis is a rapidly expanding area of synthetic chemistry which is being widely exploited in the search for new medicinally important compounds using combinatorial techniques. In recent decades, a large number of reports related to solid-phase synthesis of heterocycles have appeared because of the wide variety in their biological activity. In this review, we report the important role of solid-phase synthesis in the synthesis of oxygen-bearing heterocycles.     

天然产物化学研究的挑战和机遇

本文论述了目前我国天然产物化学研究中所存在的问题以及面临的挑战和机遇,同时就如何促进我国天然产物的新结构、新功能及其合成化学等方面的原始性创新研究和相应的对策进行了评述。     

Identification of Inhibitors for Mycobacterial Protein Tyrosine Phosphatase B (MptpB) by Biology‐Oriented Synthesis (BIOS)

Protein phosphatases have recently emerged as important targets for research in chemical biology and medicinal chemistry, and new classes of phosphatase inhibitors are in high demand. BIOS (biology‐oriented synthesis) employs the criteria of relevance to nature and biological prevalidation for the design and synthesis of compound collections. In an application of the BIOS principle, an efficient solid‐phase synthesis of highly substituted indolo[2,3‐a]quinolizidines by using a vinylogous Mannich–Michael reaction in combination with phosgene‐ or acid‐mediated ring closure was developed. Screening of this library for phosphatase inhibitors yielded a new inhibitor class for the Mycobacterium tuberculosis phosphatase MptpB.     

Click Chemistry: Diverse Chemical Function from a Few Good Reactions

Examination of nature's favorite molecules reveals a striking preference for making carbon–heteroatom bonds over carbon–carbon bonds—surely no surprise given that carbon dioxide is nature's starting material and that most reactions are performed in water. Nucleic acids, proteins, and polysaccharides are condensation polymers of small subunits stitched together by carbon–heteroatom bonds. Even the 35 or so building blocks from which these crucial molecules are made each contain, at most, six contiguous C−C bonds, except for the three aromatic amino acids. Taking our cue from nature's approach, we address here the development of a set of powerful, highly reliable, and selective reactions for the rapid synthesis of useful new compounds and combinatorial libraries through heteroatom links (C−X−C), an approach we call “click chemistry”. Click chemistry is at once defined, enabled, and constrained by a handful of nearly perfect “spring‐loaded” reactions. The stringent criteria for a process to earn click chemistry status are described along with examples of the molecular frameworks that are easily made using this spartan, but powerful, synthetic strategy.     

A Chemical Approach to Protein Design—Template-Assembled Synthetic Proteins (TASP)

Advances in methodology in both chemistry and molecular biology allow us to take a fresh look at protein science. Chemical synthesis of peptides and site-directed mutagenesis are now standard research tools, paving the way for the construction of new proteins with tailor-made structural and functional properties. The decisive hurdle on the way lies not in the synthesis of the molecules proper but rather in a better understanding of the complex folding pathways of polypeptide chains into spatially well-defined structures. Can the chemist use his synthetic tools to bypass the notorious “folding problem?” In this article, we present a new approach developed in our laboratory, which opens a chemical route to artificial proteins with predetermined three-dimensional structures, allowing a first step towards the synthesis of new proteins with functional properties.     

Organic Chemistry on Solid Supports

Until recently, repetitive solid-phase synthesis procedures were used predominantly for the preparation of oligomers such as peptides, oligosaccharides, peptoids, oligocarbamates, peptide vinylogues, oligomers of pyrrolin-4-one, peptide phosphates, and peptide nucleic acids. However, the oligomers thus produced have a limited range of possible backbone structures due to the restricted number of building blocks and synthetic techniques available. Biologically active compounds of this type are generally not suitable as therapeutic agents but can serve as lead structures for optimization. “Combinatorial organic synthesis” has been developed with the aim of obtaining low molecular weight compounds by pathways other than those of oligomer synthesis. This concept was first described in 1971 by Ugi.^[56f,g,59c] Combinatorial synthesis offers new strategies for preparing diverse molecules, which can then be screened to provide lead structures. Combinatorial chemistry is compatible with both solution-phase and solid-phase synthesis. Moreover, this approach is conducive to automation, as proven by recent successes in the synthesis of peptide libraries. These developments have led to a renaissance in solid-phase organic synthesis (SPOS), which has been in use since the 1970s. Fully automated combinatorial chemistry relies not only on the testing and optimization of known chemical reactions on solid supports, but also on the development of highly efficient techniques for simultaneous multiple syntheses. Almost all of the standard reactions in organic chemistry can be carried out using suitable supports, anchors, and protecting groups with all the advantages of solid-phase synthesis, which until now have been exploited only sporadically by synthetic organic chemists. Among the reported organic reactions developed on solid supports are Diels–Alder reactions, 1,3-dipolar cycloadditions, Wittig and Wittig–Horner reactions, Michael additions, oxidations, reductions, and Pd-catalyzed C? C bond formation. In this article we present a comprehensive review of the previously published solid-phase syntheses of nonpeptidic organic compounds.     

Towards the optimal screening collection: a synthesis strategy

The development of effective small-molecule probes and drugs entails at least three stages: 1) a discovery phase, often requiring the synthesis and screening of candidate compounds, 2) an optimization phase, requiring the synthesis and analysis of structural variants, 3) and a manufacturing phase, requiring the efficient, large-scale synthesis of the optimized probe or drug. Specialized project groups tend to undertake the individual activities without prior coordination; for example, contracted (outsourced) chemists may perform the first activity while in-house medicinal and process chemists perform the second and third development stages, respectively. The coordinated planning of these activities in advance of the first small-molecule screen tends not to be undertaken, and each project group can encounter a bottleneck that could, in principle, have been avoided with advance planning. Therefore, a challenge for synthetic chemistry is to develop a new kind of chemistry that yields a screening collection comprising small molecules that increase the probability of success in all three phases. Although this transformative chemistry remains elusive, progress is being made. Herein, we review a newly emerging strategy in diversity-oriented small-molecule synthesis that may have the potential to achieve these challenging goals.     

咪唑环番仿生新体系研究进展

仿生化学是当今化学的挑战性领域之一。咪唑环番是构筑仿生体系的优良基体,但迄今研究工作极少。本文简要评述了咪唑的选择性反应和咪唑衍生物的选择性合成、新型咪唑环番和咪唑鎓环番的设计合成及仿生功能研究的一些新进展。