Cyclic polymers: Methods and strategies

Cyclic polymers have different physical properties compared to their linear counterparts of the same molecular weight. These different properties could have potential impact in the production of new and exciting polymer products. For industry to commercialize such materials, cyclic polymers need to be made on large scales, have controlled molecular weight distributions, and have versatile chemical composition. This highlight article describes many of the synthetic methods and strategies for obtaining highly pure cyclic polymers, and presents kinetic attributes for some of the processes. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Chemistry and Biology of the Enediyne Anticancer Antibiotics

Novel, biologically active substances from nature often provide excitement, stimulation, challenges, and opportunities for the scientific and medical communities. Experience and wisdom dictate investigation of their chemistry and pursuit of their chemical synthesis for more often than not, the rewards for both chemistry and medicine are great. The enediyne anticancer antibiotics are a rapidly emerging class of such compounds derived from bacterial sources. Combining unprecedented and highly unusual molecular architecture, phenomenal biological activities and fascinating modes of action, these DNA cleaving compounds burst onto the scene in the latter half of the 1980s when their structures became known, and they rapidly moved to center stage. Today the enediyne family includes the neocarzinostatin chromophore, the calicheamicins, the esperamicins, and the dynemicins, and soon the number of family members is certain to increase. These molecules elicited extensive research activities in chemical, biological, and biomedical circles and inspired the design of a number of novel molecular assemblies to probe and mimic their chemical and biological actions. A new body of synthetic technology and several novel synthetic strategies have already been devised to address the challenges posed by these molecules, and several new DNA cleaving agents have been designed and synthesized. This article summarizes the chemistry and biology of the enediynes and discusses mechanistic, synthetic, molecular design, and DNA cleavage aspects associated with the field.     

A Challenging Pie to Splice: Drugging the Spliceosome

Since its discovery in 1977, the study of alternative RNA splicing has revealed a plethora of mechanisms that had never before been documented in nature. Understanding these transitions and their outcome at the level of the cell and organism has become one of the great frontiers of modern chemical biology. Until 2007, this field remained in the hands of RNA biologists. However, the recent identification of natural product and synthetic modulators of RNA splicing has opened new access to this field, allowing for the first time a chemical‐based interrogation of RNA splicing processes. Simultaneously, we have begun to understand the vital importance of splicing in disease, which offers a new platform for molecular discovery and therapy. As with many natural systems, gaining clear mechanistic detail at the molecular level is key towards understanding the operation of any biological machine. This minireview presents recent lessons learned in this emerging field of RNA splicing chemistry and chemical biology.     

Chemoselective Ligation and Modification Strategies for Peptides and Proteins

The investigation of biological processes by chemical methods, commonly referred to as chemical biology, often requires chemical access to biologically relevant macromolecules such as peptides and proteins. Building upon solid‐phase peptide synthesis, investigations have focused on the development of chemoselective ligation and modification strategies to link synthetic peptides or other functional units to larger synthetic and biologically relevant macromolecules. This Review summarizes recent developments in the field of chemoselective ligation and modification strategies and illustrates their application, with examples ranging from the total synthesis of proteins to the semisynthesis of naturally modified proteins.     

Modern Synthetic Avenues for the Preparation of Functional Fluorophores

Biomedical research relies on the fast and accurate profiling of specific biomolecules and cells in a non‐invasive manner. Functional fluorophores are powerful tools for such studies. As these sophisticated structures are often difficult to access through conventional synthetic strategies, new chemical processes have been developed in the past few years. In this Minireview, we describe the most recent advances in the design, preparation, and fine‐tuning of fluorophores by means of multicomponent reactions, C−H activation processes, cycloadditions, and biomolecule‐based chemical transformations.     

Femtochemie. Elementare Schritte chemischer Reaktionen

Femtochemistry is about the investigation and control of ultrafast elementary molecular dynamics, which are the basis of every chemical reaction. The processes finally resulting in breaking of chemical bonds or molecular structure changes take place on a time scale of only femto to picoseconds. Solely femtosecond laser pulses are fast enough to resolve these fast processes. Different techniques were developed, which make use of a combination of femtosecond pulses having a relative temporal delay, in order to get access to the dynamics even in complex molecules. The knowledge of the elementary processes allows for a better understanding of the reaction mechanisms and their dependence on environmental conditions. The interaction with the molecules even before the final reaction path is entered, opens up new exciting possibilities for the control of chemical processes. A specific manipulation of the molecular dynamics using adapted pulse shapes appears to be realistic also for complex reactions and systems. The evolutionary optimization strategies, which exploit the experimental results as feedback, make selective chemistry come true even without knowledge of all system parameters.     

Lipidated ras and rab peptides and proteins--synthesis, structure, and function

Chemical biology can be defined as the study of biological phenomena from a chemical approach. Based on the analysis of relevant biological phenomena and their structural foundation, unsolved problems are identified and tackled through a combination of chemistry and biology. Thus, new synthetic methods and strategies are developed and employed for the construction of compounds that are used to investigate biological procedures. Solid-phase synthesis has emerged as the preferred method for the synthesis of lipidated peptides, which can be chemoselectively ligated to proteins of the Ras superfamily. The generated peptides and proteins have solved biological questions in the field of the Ras-superfamily GTPases that are not amendable to chemical or biological techniques alone.     

Cooperative self-assembly: producing synthetic polymers with precise and concise primary structures

The quest to construct mechanically interlocked polymers, which present precise monodisperse primary structures that are produced both consistently and with high efficiencies, has been a daunting goal for synthetic chemists for many years. Our ability to realise this goal has been limited, until recently, by the need to develop synthetic strategies that can direct the formation of the desired covalent bonds in a precise and concise fashion while avoiding the formation of unwanted kinetic by-products. The challenge, however, is a timely and welcome one, as a consequence of, primarily, the potential for mechanically interlocked polymers to act as dynamic (noncovalent) yet robust (covalent) new materials for a wide array of applications. One such strategy which has been employed widely in recent years to address this issue, known as Dynamic Covalent Chemistry (DCC), is a strategy in which reactions operate under equilibrium and so offer elements of "proof-reading" and "error-checking" to the bond forming and breaking processes such that the final product distribution always reflects the thermodynamically most favourable compound. By coupling DCC with template-directed protocols, which utilise multiple weak noncovalent interactions to pre-organise and self-assemble simpler small molecular precursors into their desired geometries prior to covalent bond formation, we are able to produce compounds with highly symmetric, robust and complex topologies that are otherwise simply unobtainable by more traditional methods. Harnessing these strategies in an iterative, step-wise fashion brings us ever so much closer towards perfecting the controlled synthesis of high order main-chain mechanically interlocked polymers. This tutorial review focuses (i) on the development of DCC-namely, the formation of dynamic imine bonds-used in conjunction with template-directed protocols to afford a variety of mechanically interlocked molecules (MIMs) and ultimately (ii) on the synthesis of highly ordered poly[n]rotaxanes with high conversion efficiencies.     

FDCA基聚酯的合成、性能及应用研究进展

生物质资源是一种储量丰富的可再生资源。生物质资源的高效利用不仅具有非常巨大的经济和生态价值,而且对新能源与生物基合成材料的可持续发展战略具有重大意义。由植物纤维素等生物质材料经生物或者简单化学过程处理,可获得丰富的生物基单体2,5-呋喃二甲酸(FDCA)。FDCA可用于生物基聚酯材料的合成。FDCA系列聚酯材料性能优异,可作为由石油基单体对苯二甲酸(PTA)而合成的芳香族聚酯材料(例如PET)的一种潜在的高性能生物可降解替代材料。本文简要说明了生物基单体FDCA的物性及制备方法,并重点阐述了包括聚呋喃二甲酸乙二酯(PEF)与聚呋喃二甲酸丁二酯(PBF)等一系列FDCA基聚酯材料的合成及性质,同时对FDCA基聚酯材料的应用进展进行了简要介绍,最后对FDCA基聚酯生物基合成材料的发展前景作了初步展望。     

Synthesis,structure, and function of internally functionalized dendrimers

The past three decades have witnessed an exponential increase in the structural diversity and applications of dendrimers, spanning across drug delivery and diagnostics, protein, and enzyme mimicry, solubility enhancement, coatings, light harvesting, and catalysis. The dendrimer community has recently focused on internally functionalized dendrimers (IFDs) owing to their advanced design and functionality. The synthesis of IFDs relies on advanced orthogonal chemistries and/or (de)protection schemes, as well as careful purification to minimize polydispersity of composition and molecular weight. The studies published on IFDs, however, lay scattered across the chemical literature, and a comprehensive presentation of structural rationale, synthetic procedures, and technologically relevant applications is missing. To address this need, this review presents a comprehensive collection and discussion of all available studies on IFDs, detailing their methods of synthesis and their structure–function correlations. The wide variety of internal functionalities, including hydroxyl, amine, carboxylic acid, allyl, alkyne, and imidazole groups, enables myriad applications in biochemistry, chemical and biomedical engineering, and material science. Particular focus is given to IFDs that are amenable to modular synthetic strategies, which promote higher synthetic yield and scalability, and therefore possess stronger translational and commercial potential. As such, this review guides research groups pursuing the difficult task of IFD rational design and synthesis providing them a concise roadmap to their mission.     

Tackling the chemical diversity of microbial nonulosonic acids – a universal large-scale survey approach

Nonulosonic acids, commonly referred to as sialic acids, are a highly important group of nine-carbon sugars common to all domains of life. They all share biosynthetic and structural features, but otherwise display a remarkable chemical diversity. In humans, sialic acids cover all cells which makes them important for processes such as cellular protection, immunity and brain development. On the other hand, sialic acids and other nonulosonic acids have been associated with pathological processes including cancer and viral infections. In prokaryotes, nonulosonic acids are commonly associated with pathogens, which developed through molecular mimicry a strategy to circumvent the host''s immune response. However, the remarkably large chemical diversity of prokaryotic nonulosonic acids challenges their discovery, and research on molecular characteristics essential for medical applications are often not feasible. Here, we demonstrate a novel, universal large-scale discovery approach that tackles the unmapped diversity of prokaryotic nonulosonic acids. Thereby, we utilize selective chemical labelling combined with a newly established mass spectrometric all-ion-reaction scanning approach to identify nonulosonic acids and other ulosonic acid-like sugars. In doing so, we provide a first molecular-level comparative study on the frequency and diversity across different phyla. We not only illustrate their surprisingly wide-spread occurrence in non-pathogenic species, but also provide evidence of potential higher carbon variants. Many biomedical studies rely on synthetic routes for sialic acids, which are highly demanding and often of low product yields. Our approach enables large-scale exploration for alternative sources of these highly important compounds.

A novel large-scale survey approach for microbial nonulosonic acids (sialic acids) including a first molecular level comparative study is presented.     

Adventures in Carbohydrate Chemistry: New Synthetic Technologies, Chemical Synthesis, Molecular Design, and Chemical Biology A list of abbreviations can be found at the end of this article. Telemachos Charalambous was an inspiring teacher at the Pancyprian Gymnasium, Nicosia, Cyprus

The field of carbohydrate chemistry has occupied the minds and hearts of many scientists for over a hundred years and, as we enter the twenty-first century, it continues to be both vigorous and challenging. Among the most exciting aspects of organic chemistry in the last few decades has been the interplay between the specialized subdisciplines of carbohydrate chemistry and total synthesis, each enabling and advancing the other in new directions and towards greater heights. In this review article we highlight our own adventures at the interface of these disciplines, which were driven for the most part by objectives in chemical synthesis and chemical biology. Specifically, we describe our interests and efforts to utilize carbohydrates as starting materials for total synthesis, to invent and develop new synthetic technologies for carbohydrate synthesis, to construct complex oligosaccharides in solution or on solid support, and to utilize carbohydrate templates as scaffolds for peptide mimetics and for molecular diversity construction. Finally, applications of the developed synthetic strategies and enabling technologies towards the solution of biologically significant problems are discussed.     

Stabilization of p-block organoelement terminal hydroxides, thiols, and selenols requires newer synthetic strategies

Metal hydroxides represent a very interesting and highly useful class of compounds that have been known to chemists for a very long time. While alkali and alkaline earth metal hydroxides (s‐block) are commonplace chemicals in terms of their abundance and their use in a chemical laboratory as bases, the interest in Brønsted acidic molecular terminal hydroxides of p‐block elements, such as aluminum and silicon, has been of recent origin, with respect to the variety of applications these compounds can offer both in materials science and catalysis. Moreover, these systems are environmentally friendly, relative to the metal halides, owing to their ‐OH functionality (resembling that of water). Design and conceptualization of the corresponding terminal thiols, selenols, and tellurols (M? SH, M? SeH, and M? TeH) offer even more challenging problems to synthetic inorganic chemists. This concept summarizes some of the recent strategies developed to stabilize these otherwise very unstable species. The successful preparation of a number of silicon trihydroxides a few years back resulted in the generation of several model compounds for metal–silicates. The recent synthesis of unusual aluminum compounds such as RAl(OH)₂, RAl(SH)₂, and RAl(SeH)₂ with terminal EH (E=O, Se, or Se) groups is likely to change the ways in which some of the well‐known catalytic conversions are being carried out. The need for very flexible and innovative synthetic strategies to achieve these unusual compounds is emphasized in this concept.     

Supramolecular Strategies for Controlling Reactivity within Confined Nanospaces

Nanospaces are ubiquitous in the realm of biological systems and are of significant interest among supramolecular chemists. Understanding chemical behavior within nanospaces offers new perspectives on biological phenomena in nature and opens the way to highly unusual and selective forms of catalysis. Supramolecular chemistry exploits weak, yet effective, intermolecular interactions such as hydrogen bonding, metal‐ligand coordination, and the hydrophobic effect to assemble nano‐sized molecular architectures, providing reactions with remarkable rate acceleration, substrate specificity, and product selectivity. In this minireview, the focus is on the strategies that supramolecular chemists use to emulate the efficiency of biological processes, and elucidating how chemical reactivity is efficiently controlled within well‐defined nanospaces. Approaches such as orientation and proximity of substrate, transition‐state stabilization, and active‐site incorporation will be discussed.     

Recent Advances in One-Pot Modular Synthesis of 2-Quinolones

It is known that 2-quinolones are broadly applicable chemical structures in medicinal and agrochemical research as well as various functional materials. A number of current publications about their synthesis and their applications emphasize the importance of these small molecules. The early synthetic chemistry originated from the same principle of the classical Friedländer and Knorr procedures for the preparation of quinolines. The analogous processes were developed by applying new synthetic tools such as novel catalysts, the microwave irradiation method, etc., whereas recent innovations in new bond forming reactions have allowed for novel strategies to construct the core structures of 2-quinolones beyond the bond disconnections based on two classical reactions. Over the last few decades, some reviews on structure-based, catalyst-based, and bioactivity-based studies have been released. In this focused review, we extensively surveyed recent examples of one-pot reactions, particularly in view of modular approaches. Thus, the contents are categorized as three major sections (two-, three-, and four-component reactions) according to the number of reagents that ultimately compose atoms of the core structures of 2-quinolones. The collected synthetic methods are discussed from the perspectives of strategy, efficiency, selectivity, and reaction mechanism.     

Hydratases involved in nitrile conversion: screening, characterization and application

The discovery of new enzymes with greater activity and specificity opens new, simple routes for synthetic processes, and consequently, new methods to solve environmental problems. A number of nitrile-related enzymes have been screened over the past few years for use in developing synthetic applications. Microbial nitrile hydratase (NHase) has great potential as a catalyst in organic chemical processing because the enzyme can convert nitriles to the corresponding higher value amides under mild conditions, and has now been applied to the industrial productions of acrylamide and nicotinamide. Particularly, the former production is the first successful example of a bioconversion process for the manufacture of a commodity chemical. The characterization of the enzyme at the molecular level has provided new insights into how the molecular structure determines the enzyme function, and how the regulatory system controls the expression of the enzyme genes to improve the enzyme and the NHase-dependent process.     

Rational design and functional evolution of targeted peptides for bioanalytical applications

The complicated, highly dynamic and diverse nature of biosystems brings great challenges to the specific analysis of molecular processes of interest. Nature provides antibodies for the specific recognition of antigens, which is a straight-forward way for targeted analysis. However, there are still limitations during the practical applications due to the big size of the antibodies, which accelerate the discovery of small molecular probes. Peptides built from various optional building blocks and easily achieved by chemical synthetic approaches with predictable conformations, are versatile and can act as tailor-made targeting vehicles. In this mini review, we summarize the recent developments in the discovery of novel peptides for bioanalytical and biomedical applications. Progresses in peptide-library design and selection strategies are presented. Recent achievements in the peptide-guided detection, imaging and disease treatment are also focused.     

Transient Substrate‐Induced Catalyst Formation in a Dynamic Molecular Network

In biology enzyme concentrations are continuously regulated, yet for synthetic catalytic systems such regulatory mechanisms are underdeveloped. We now report how a substrate of a chemical reaction induces the formation of its own catalyst from a dynamic molecular network. After complete conversion of the substrate, the network disassembles the catalyst. These results open up new opportunities for controlling catalysis in synthetic chemical systems.     

Green Synthetic Approach: An Efficient Eco-Friendly Tool for Synthesis of Biologically Active Oxadiazole Derivatives

Green synthetic protocol refers to the development of processes for the sustainable production of chemicals and materials. For the synthesis of various biologically active compounds, energy-efficient and environmentally benign processes are applied, such as microwave irradiation technology, ultrasound-mediated synthesis, photo-catalysis (ultraviolet, visible and infrared irradiation), molecular sieving, grinding and milling techniques, etc. Thesemethods are considered sustainable technology and become valuable green protocol to synthesize new drug molecules as theyprovidenumerous benefits over conventional synthetic methods.Based on this concept, oxadiazole derivatives are synthesized under microwave irradiation technique to reduce the formation of byproduct so that the product yield can be increased quantitatively in less reaction time. Hence, the synthesis of drug molecules under microwave irradiation follows a green chemistry approach that employs a set of principles to minimize or remove the utilization and production of hazardous toxic materials during the design, manufacture and application of chemical substances.This approach plays a major role in controlling environmental pollution by utilizing safer solvents, catalysts, suitable reaction conditions and thereby increases the atom economy and energy efficiency. Oxadiazole is a five-membered heterocyclic compound that possesses one oxygen and two nitrogen atoms in the ring system.Oxadiazole moiety is drawing considerable interest for the development of new drug candidates with potential therapeutic activities including antibacterial, antifungal, antiviral, anticonvulsant, anticancer, antimalarial, antitubercular, anti-asthmatic, antidepressant, antidiabetic, antioxidant, antiparkinsonian, analgesic and antiinflammatory, etc. This review focuses on different synthetic approaches of oxadiazole derivatives under microwave heating method and study of their various biological activities.     

Facile synthesis of a diverse library of mono-3-substituted β-cyclodextrin analogues

Substituted cyclodextrins (CDs) have many applications, but synthetic challenges have limited the derivatives that can routinely be accessed. In particular, although there is considerable interest in selective derivatization at the 2- and 3-hydroxyls on the secondary face, since bulky guest molecules are most likely to project through this larger aperture, syntheses of such derivatives have required arduous procedures that afford poor yields, limiting their accessibility and utility. We address this challenge via synthetic strategies that allow facile creation of diverse libraries of water-soluble mono-3-substituted-β-cyclodextrins, via the commercially available mono-3-amino-β-cyclodextrin. The power of these strategies is confirmed through synthesis of twenty water-soluble cyclodextrin analogues with amide, thioureas or urea linkers, using one-pot reactions producing ≥55% yields and purifications that do not require chromatography. This work opens new possibilities for the design of selective host molecules for use in supramolecular chemistry, chemical separations, pharmaceutical formulations, and calibration of molecular simulations.