The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion

Structurally diverse macrocycles and medium‐sized rings (9–24 membered scaffolds, 22 examples) can be generated through a telescoped acylation/ring‐expansion sequence, leading to the insertion of linear fragments into cyclic β‐ketoesters without performing a discrete macrocyclization step. The key β‐ketoester motif is regenerated in the ring‐expanded product, meaning that the same sequence of steps can then be repeated (in theory indefinitely) with other linear fragments, allowing macrocycles with precise substitution patterns to be “grown” from smaller rings using the successive ring‐expansion (SuRE) method.     

Synthesis of Unprecedented Scaffold Diversity

Building a better library : The synthesis of a library of natural‐product‐like small molecules with unprecedented scaffold diversity has been reported (see scheme; Ns=nosylate). The library represents a significant advancement in the capability of synthetic chemists to generate structurally diverse and complex small molecules in a rapid manner.

     

Synthesis and Spectra of Bichromophore Compounds Containing Oxazole or Oxadiazole Ring

Fifteen of the bichromophore compounds containing oxazole or oxidation ring have been synthesized. Their structures have been identified by IR, 1H NMR spectra and elemental analysis. The UV spectra, fluorescence spectra and the laser conversion efficiencies have been determined . The results of determination show that the absorption and emission spectra Pf the bichromophore compounds are different from those of the corresponding single chromophore compounds.     

Diversity‐Oriented Approach for Chemical Biology

Synthetic molecules that modulate and probe biological events are critical tools in chemical biology. Utilizing combinatorial and diversity‐oriented synthetic strategies, access to large numbers of small molecules is becoming more and more feasible, and research groups in this field can take advantage of the power of chemical diversity. Since the majority of early studies were focused on the discovery of compounds that perturb protein functions, diversity‐based approaches are often considered as therapeutic lead discovery tactics. However, the diversity‐oriented approach can also be applied to advance distinct aims, such as target protein identification, or the development of imaging probes and sensors. This review provides a personal perspective of the chemical‐diversity‐based approach and how this principle can be adapted to various chemical biology studies.     

A Retrospective on the Design and Synthesis of Novel Molecules through a Strategic Consideration of Metathesis and Suzuki–Miyaura Cross‐Coupling

Synergy in synthesis : Strategic consideration of metathesis and Suzuki–Miyaura (SM) cross‐coupling for C? C bond‐formation processes has opened up new and “green” synthetic routes to various complex targets. The use of this synergistic combination for the synthesis of supramolecular ligands, polyaromatic compounds, and complex natural products is covered in this Focus Review.

     

Applications of Multicomponent Reactions to the Synthesis of Diverse Heterocyclic Scaffolds

The sequencing of multicomponent reactions (MCRs) and subsequent cyclization reactions is a powerful stratagem for the rapid synthesis of diverse heterocyclic scaffolds. The optimal MCR is sufficiently flexible that it can be employed to generate adducts bearing a variety of functional groups that may then be selectively paired to enable different cyclization manifolds, thereby leading to a diverse collection of products. The growing interest in diversity‐oriented synthesis has led to increased attention to this paradigm for library synthesis, which has inspired many advances in the design and implementation of MCRs for the construction of diverse heterocyclic scaffolds.     

Searching Hit Potential Antimicrobials in Natural Compounds Space against Biofilm Formation

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces and thus play a significant role in the persistence of bacterial infection and resistance to antimicrobial. About 65% and 80% of microbial and chronic infections are associated with biofilm formation, respectively. The increase in infections by multi-resistant bacteria instigates the need for the discovery of novel natural-based drugs that act as inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved in the biofilm formation, represents a potential approach for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. This study aimed to search for natural products capable of inhibiting the Caulobacter crescentus enzyme PleD. For this purpose, 224,205 molecules from the natural products ZINC15 database, have been evaluated through molecular docking and molecular dynamic simulation. Our results suggest trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new inhibitors of the PleD protein and hence blocking the biofilm formation.     

Supramolecular Tools to Improve Wound Healing and Antioxidant Properties of Abietic Acid: Biocompatible Microemulsions and Emulgels

Abietic acid, a naturally occurring fir resin compound, that exhibits anti-inflammatory and wound-healing properties, was formulated into biocompatible emulgels based on stable microemulsions with the addition of a carbamate-containing surfactant and Carbopol^® 940 gel. Various microemulsion and emulgel formulations were tested for antioxidant and wound-healing properties. The chemiluminescence method has shown that all compositions containing abietic acid have a high antioxidant activity. Using Strat-M^® skin-modelling membrane, it was found out that emulgels significantly prolong the release of abietic acid. On Wistar rats, it was shown that microemulsions and emulgels containing 0.5% wt. of abietic acid promote the rapid healing of an incised wound and twofold tissue reinforcement compared to the untreated group, as documented by tensiometric wound suture-rupture assay. The high healing-efficiency is associated with a combination of antibacterial activity of the formulation components and the anti-inflammatory action of abietic acid.     

萘磺酸型离子配合物的合成及其分子识别性能

常温反应条件下制备了4个基于乙二胺和1,5-萘二磺酸的配位化合物[M(en)(H_2O)_4]·1,5-nds·(H_2O)_2(M=Ni(1),Co(2),Cd(3),Cu(4),nds=1,5-萘二磺酸;en=乙二胺),并通过红外光谱、元素分析、X射线单晶衍射、X射线粉末衍射和热重分析等技术手段确定了其晶体结构。结构分析表明,该系列配合物属于同构体系,单斜晶系,C2/c空间群。以配合物1为例,其晶胞参数为a=1.69026(19)nm,b=1.01373(11)nm,c=1.3448(3)nm,α=90°,β=120.2650°,γ=90°,V=1.9901(5)nm~3,Z=4,Dc=1.713 g/cm~3,F(000)=1072,R_1=0.0326,wR_2=0.0867。该系列配合物的中心金属为六配位模式,与来自乙二胺的2个N原子和4个H_2O中的氧原子配位。游离水与磺酸氧和配位水之间存在着丰富的氢键作用,构筑成三维的网络结构。测定了以Cd为中心金属配合物3的荧光光谱,发现其在对于甲醇的小分子识别性能方面具有应用前景。     

新型吡啶环液晶化合物的合成及性能

以2-溴-5-吡啶甲醛和5-溴-2-吡啶甲醛为起始原料,合成出4种新型含吡啶环二联芳基和三联芳基化合物,总收率20%~30%。 热性能研究结果表明,二联芳基化合物未呈现出液晶相,而三联芳基化合物在加热和冷却过程中均表现向列相液晶态,且当氮原子位于正丁基的间位时,其与不含氮原子的三联苯化合物(2c)相比,熔点降低了11.7 ℃,清亮点升高6.3 ℃,液晶相区拓宽了18 ℃,表现出了良好的热性能。 光电性能测试结果表明,用吡啶环替代苯环后,化合物的光学各向异性值均较参比化合物(1c或2c)增大;当N原子位于正丁基的邻位的化合物,介电各向异性值较参比化合物增大,且液晶的阈值电压、饱和电压均降低。 通过对三环同分异构体化合物的不同构象能量态的计算分析,解释了介电各向异性的变化规律。     

Combinatorial chemistry approach to chiral catalyst engineering and screening: rational design and serendipity

An efficient asymmetric catalyst relies on the successful combination of a large number of interrelated variables, including rational design, intuition, persistence, and good fortune-not all of which are necessarily well-understood; this renders such practice largely empirical. As a result, the possibility of using combinatorial chemistry methods in asymmetric catalysis research has been widely recognized to be highly desirable. In this account, we attempt to show the principle and application of combinatorial approach in the discovery of chiral catalysts for enantioselective reactions. The concept focuses on the strategy for the creation of a modular chiral catalyst library by two-component ligand modification of metal ions on the basis of molecular recognition and assembly. The self-assembled chiral catalyst with two different ligands indeed exhibited synergistic effects in terms of both enantioselectivity and activity in comparison with its corresponding homocombinations in many reactions. The examples described in this paper demonstrated the powerfulness of combinatorial approach for the discovery of novel chiral catalyst systems, particularly for the development of highly efficient, enantioselective, and practical catalysts for enantioselective reactions. We hope this concept will stimulate further work on the discovery of more highly efficient and enantioselective catalysts, as well as unexpected classes of catalysts or catalytic enantioselective reactions in the future with the help of a combinatorial chemistry approach.     

Type II Intramolecular [5+2] Cycloaddition: Facile Synthesis of Highly Functionalized Bridged Ring Systems

A type II intramolecular oxidopyrylium‐mediated [5+2] cycloaddition reaction allows the efficient and diastereoselective formation of various highly functionalized and synthetically challenging bridged seven‐membered ring systems (such as bicyclo[4.4.1]undecane, bicyclo[4.3.1]decane, bicyclo[5.4.1]dodecane, and bicyclo[6.4.1]]tridecane). This simple, thermal, direct transformation has a broad substrate scope and is high yielding, with high functional‐group tolerance and unique endo selectivity. The highly strained tricyclic cores of ingenol mebutate (picato) and cyclocitrinol are synthesized efficiently and diastereoselectively using this methodology.     

苯基磺酸官能化分子筛催化合成香豆素类化合物

在苯基磺酸官能化介孔分子筛催化剂作用下 ,取代苯酚和乙酰乙酸乙酯经Pechmann缩合反应合成系列取代香豆素类化合物 .该催化合成反应具有条件温和、产物容易分离、收率高等优点 .考察了不同位置取代羟基对该缩合反应的影响 .结果表明 ,间位羟基有利于香豆素衍生物的生成 ,提高反应收率 ,对位羟基次之 .证实了该固体酸催化活性位为磺酸Br nsted型质子酸     

The Genus Cladosporium: A Rich Source of Diverse and Bioactive Natural Compounds

Fungi are renowned as one of the most fruitful sources of chemodiversity and for their ubiquitous occurrence. Among the many taxonomic groupings considered for the implications deriving from their biosynthetic aptitudes, the genus Cladosporium stands out as one of the most common in indoor environments. A better understanding of the impact of these fungi on human health and activities is clearly based on the improvement of our knowledge of the structural aspects and biological properties of their secondary metabolites, which are reviewed in the present paper.     

Efficient and Modular Synthesis of New Structurally Diverse Functionalized [n]Paracyclophanes by a Ring‐Distortion Strategy

With the goal of synthesizing new [n]paracyclophanes, the expansion of the scope of a strategy originally disclosed by Winterfeldt et al., was investigated. This approach involves sequential Diels–Alder/retro‐Diels–Alder reactions, the applications of which have been constrained so far to steroid derivatives. An efficient access to new functionalized [9]‐, [10]‐, and [16]paracyclophanes, including original cage architectures, was developed from readily available building blocks using thermal electrocyclization and a cycloaddition/cycloreversion sequence as the key steps.     

Total Synthesis of Ciguatoxin

Something fishy : Ciguatoxin (see structure) is one of the principal toxins involved in ciguatera poisoning and the target of a total synthesis involving the coupling of three segments. The key transformations in this synthesis feature acetylene–dicobalthexacarbonyl complexation.