Alkaloid Synthesis via Gold-Catalyzed Carbon-Carbon Bond Formation Using Enamine-type Nucleophile

In this account, various types of cyclizations/cycloisomerizations of alkyne substrates with internal enamine-type nucleophiles including enamide, enaminone, enaminoester and in situ generated enamine in the presence of electrophilc transition metal catalysts (Pt, Rh, Cu, Au) are firstly introduced. Then, the applications of the gold-catalyzed reactions in the synthesis of an array of alkaloids are discussed. These natural products feature heterocyclic structural motifs such as pyridine, azaanthraquinone, pyridoacridine, pyrrole, indole, indolenine and carbazole, as well as chiral tetrahydroindolizine, azocine units and six-membered carbocycles bearing a quaternary carbon center.     

Gold-Catalyzed Polycyclization Toward Natural Products Synthesis

Over the last years, gold catalysis has gained considerable significance in organic synthesis, since it allows atom economy and synthetic efficiency for the transformation of relatively simple substrates into valuable, highly complex molecular architectures. The gold-catalyzed polycyclization reactions of alkynes and enynes have been particularly successful toward the synthesis of natural products. This review highlights the recent developments in polycyclization area according to the key gold-catalyzed step.     

Gold-Catalyzed Alkynylation: Acetylene-Transfer instead of Functionalization

Over the last fifteen years, gold has been raised from the status of an inert noble metal to one of the most-often-used catalysts in synthetic chemistry. The functionalization of the triple bond of alkynes has been especially successful in this respect. In contrast, gold-catalyzed alkynylation reactions only began to emerge in 2007. Since then, three different approaches have been successfully used for this transformation. 1) Gold nanoparticles have been shown to promote catalytic cycles based on the oxidative arylation of aryl halides to give a “palladium-free Sonogashira reaction”. 2) The use of benziodoxol(on)e hypervalent iodine compounds as oxidative alkynylation reagents has allowed the C H functionalization of electron-rich heterocycles under mild conditions with a very broad functional-group tolerance. 3) The use of iodobenzene acetate or Selectfluor as an external oxidant has led to the first alkynylation methods based on direct C H/C H coupling reactions. In only six years, gold-catalyzed alkynylation methods have grown from non-existent to useful synthetic procedures for the synthesis of structurally diverse alkynes. Considering that acetylenes are among the most-important building blocks for applications in synthetic chemistry, chemical biology, and materials science, there is tremendous potential for the further development of gold-catalyzed alkynylation reactions in the future.     

Rendering Conventional Molecular Fingerprints for Virtual Screening Independent of Molecular Complexity and Size Effects

Molecular complexity and size effects represent a known complication of fingerprint similarity searching and virtual screening that often leads to an increase in false‐positive rates and a decrease in hit rates. In standard fingerprints, differences in the complexity of reference and database molecules lead to different fingerprint bit densities, which negatively affects similarity search calculations, in particular, when fingerprints of reference molecules have higher bit density than corresponding fingerprints of database compounds. In pharmaceutical research, this is the case in many practical virtual screening applications when chemically optimized reference molecules are used. Herein we introduce an intuitive computational method to make standard fingerprints such as structural keys or pharmacophore feature fingerprints independent of molecular complexity and size effects. This is achieved by applying the concept of 'balanced codes' originating in computer science. Following this approach, binary fingerprints are transformed by incorporating the complement of their bit patterns. This straightforward transformation produces fingerprint representations with characteristic bit patterns that have exactly half of their bit positions set on, corresponding to a constant bit density of 50 % for all test compounds, regardless of their complexity and size. In similarity search calculations in the presence of complexity effects of increasing magnitude, transformed structural key and pharmacophore fingerprints display consistently better performance than their unmodified counterparts and recover active compounds in cases where the original fingerprints fail.     

Gold-Catalyzed Cascade Reactions of Alkynes for Construction of Polycyclic Compounds

The development of cascade reactions is an area of considerable interest in modern organic chemistry. Efficient cascade reactions realize the economical synthesis of complex target molecules through multiple bond formations in a single operation. Elementary reactions that form fewer waste products are desirable in terms of atom economy and in order to suppress side product formation in sequential processes. Recent advances in homogeneous gold catalysis have opened up further possibilities for cascade reactions. In this review, recent advances in gold-catalyzed cascade cyclizations of alkynes are summarized. In particular, cascade reactions based on nucleophilic/electrophilic addition, carbene cyclopropanation/insertion, ring expansion, and cycloaddition are highlighted. Notably, many of the cascade reactions shown in this mini-review feature no theoretical waste products.     

Molecular Redistribution and Molecular Averaging: Disproportionation of Paraffins via Bifunctional Catalysis

Paraffin disproportionation via molecular redistribution (MR) and molecular averaging (MA) couples paraffin dehydrogenation and olefin hydrogenation to olefin metathesis and presents a unique example of bifunctional catalysis. In this paper we will present a series of applications of the MR/MA chemistry in refining and petrochemical industries. The thermodynamic aspects of the MR/MA chemistry and parameters influencing the catalyst performance will be discussed. We will also report the catalyst regeneration related to coke deposition and sulfur poisoning. Furthermore, the MR technology for upgrading liquid petroleum gas is scaled up in pilot plant. MR/MA provides a simple process of paraffin disproportionation which can be accomplished otherwise only via complex combinations of other existing technologies.     

Gold-Catalyzed Hydrofunctionalizations and Spiroketalizations of Alkynes as Key Steps in Total Synthesis

This contribution summarizes the application of homogeneous gold catalysis in hydrofunctionalization and spiroketalization reactions in total synthesis, the most frequent applications of gold catalysis in that sector.     

Estolide Molecular Weight Distribution via Gel Permeation Chromatography

Using the universal calibration and the Mark-Houwink equation (MHE) (), three batches of oleic estolide acids and their corresponding 2-ethylhexyl esters were characterized using gel permeation chromatography (GPC). The MHE parameters in tetrahydrofuran (THF) at 40 °C were determined (for acids: α = 0.442 ± 0.003 and log₁₀K =2.505 ± 0.007, for esters: α =0.531 ± 0.006 and log₁₀K =2.794 ± 0.018). The fits of the GPC chromatograms yielded also the oligomeric composition of the estolides, which can be used to calculate the estolide number (EN) of an estolide mixture, and other molecular-weight distribution parameters, such as number-average molecular weight (M_n ), weight-average molecular weight (M_w ), and dispersity (Ð). Using the Deming line fit, we concluded that the GPC should be expected to be approximately three times more sensitive than the currently used methods for determination of EN values.     

Bulk Gold-Catalyzed Oxidations of Amines and Benzyl Alcohol Using Amine N-Oxides as Oxidants

Abstract  

Bulk gold powder (~50 μm) catalyzes the oxidative dehydrogenation of amines to give imines using amine N-oxides (R₃N-O) as the oxidant. The reaction of dibenzylamine (PhCH₂–NH–CH₂Ph) with N-methylmorpholine N-oxide (NMMO) in the presence of gold powder at 60 °C produced N-benzylidenebenzylamine (PhCH=N–CH₂Ph) in 96% yield within 24 h. Benzyl alcohol was oxidized by NMMO to benzaldehyde in >60% yield in the presence of gold powder. Although O₂ was previously shown to oxidize amines in the presence of bulk gold, it is surprising that gold is also capable of catalyzing the oxidation of amines using amine oxides, which are chemically so different from O₂.     

Gold-Catalyzed Migration of Propargyl Acetate as an Entry into the Total Synthesis of Natural Products

Gold catalysis has emerged over the last two decades as a protocole of choice for the efficient and selective activation of a variety of organic functional groups. This has served to the total synthesis of natural products at several occasions. In this context, the gold-catalyzed migration (1,2- or 1,3-) of propargyl acetates has been particularly used. This review highlights these different synthetic developments which are presented according to the involved mechanisms.     

Gaseous Mixtures Separation via Chemically-Activated Nano Silica-Modified Carbon Molecular Sieves

Silicon - The goal of this research was to study the efficiency of the silica-modified, highly selective synthesized carbon molecular sieves for nitrogen separation in the methane purification...     

Targeting Cytokines,Pathogen-Associated Molecular Patterns,and Damage-Associated Molecular Patterns in Sepsis via Blood Purification

Sepsis is characterized by a dysregulated immune response to infections that causes life-threatening organ dysfunction and even death. When infections occur, bacterial cell wall components (endotoxin or lipopolysaccharide), known as pathogen-associated molecular patterns, bind to pattern recognition receptors, such as toll-like receptors, to initiate an inflammatory response for pathogen elimination. However, strong activation of the immune system leads to cellular dysfunction and ultimately organ failure. Damage-associated molecular patterns (DAMPs), which are released by injured host cells, are well-recognized triggers that result in the elevation of inflammatory cytokine levels. A cytokine storm is thus amplified and sustained in this vicious cycle. Interestingly, during sepsis, neutrophils transition from powerful antimicrobial protectors into dangerous mediators of tissue injury and organ dysfunction. Thus, the concept of blood purification has evolved to include inflammatory cells and mediators. In this review, we summarize recent advances in knowledge regarding the role of lipopolysaccharides, cytokines, DAMPs, and neutrophils in the pathogenesis of sepsis. Additionally, we discuss the potential of blood purification, especially the adsorption technology, for removing immune cells and molecular mediators, thereby serving as a therapeutic strategy against sepsis. Finally, we describe the concept of our immune-modulating blood purification system.     

Gold Catalysis: β‐Ketonaphthalenes via Molecular Gymnastics of 1,6‐Diyne‐4‐en‐3‐ols

1,6‐Diyne‐4‐en‐3‐ols with one terminal alkyne were applied as test substrates for a possible dual catalyzed cyclization. Instead of a dual catalysis cycle, naphthyl ketone derivatives were obtained as single products. The regioselectivity of the obtained products is unprecedented. Instead of the expected naphthyl ketones bearing the keto group in the α‐position, the keto group is positioned in the ß‐position of the naphthyl skeleton by a complex rearrangement of the starting materials.     

乳液聚合合成高分子量支化聚苯乙烯

以α-甲基丙烯酸-3-巯基己酯(MHM)为链转移剂单体,过硫酸钾(PPDS)为引发剂,十二烷基苯磺酸钠(LAS)为乳化剂,通过乳液聚合合成支化聚苯乙烯。采用核磁共振氢谱(1H-NMR)和三检测体积排除色谱(TD-SEC)对支化聚苯乙烯进行了表征分析。结果表明:乳液聚合可以合成较窄分子量分布的高分子量支化聚苯乙烯(Mw.MALLS=2.18×106g?mol?1,PDI=4.42),且表现出很高的支化程度。     

分子氧氧化二甘醇合成二甘酸

以水为溶剂,氧气为氧化剂,经Bi修饰的Pt/C为催化剂液相催化氧化二甘醇合成二甘酸,用红外光谱及核磁共振氢谱等对产物进行了表征。探讨了反应温度、反应时间、底物与催化剂质量比、水与底物体积比、氧气流量等因素对实验的影响。最佳的实验条件为:反应温度80℃,反应时间8 h,底物和催化剂的质量比值为30,水和底物的体积比值为30,氧气流量为40 mL/min。在该反应条件下,二甘酸的平均收率为95.0%,催化剂重复使用6次活性未见显著降低。     

Enhanced Deep-Learning Prediction of Molecular Properties via Augmentation of Bond Topology

Deep learning has made great strides in tackling chemical problems, but still lacks full-fledged representations for three-dimensional (3D) molecular structures for its inner working. For example, the molecular graph, commonly used in chemistry and recently adapted to the graph convolutional network (GCN), is inherently a 2D representation of 3D molecules. Herein we propose an advanced version of the GCN, called 3DGCN, which receives 3D molecular information from a molecular graph augmented by information on bond direction. While outperforming state-of-the-art deep-learning models in the prediction of chemical and biological properties, 3DGCN has the ability to both generalize and distinguish molecular rotations in 3D, beyond 2D, which has great impact on drug discovery and development, not to mention the design of chemical reactions.     

Precise Characterization of Genetic Interactions in Cancer via Molecular Network Refining Processes

Genetic interactions (GIs), such as the synthetic lethal interaction, are promising therapeutic targets in precision medicine. However, despite extensive efforts to characterize GIs by large-scale perturbation screening, considerable false positives have been reported in multiple studies. We propose a new computational approach for improved precision in GI identification by applying constraints that consider actual biological phenomena. In this study, GIs were characterized by assessing mutation, loss of function, and expression profiles in the DEPMAP database. The expression profiles were used to exclude loss-of-function data for nonexpressed genes in GI characterization. More importantly, the characterized GIs were refined based on Kyoto Encyclopedia of Genes and Genomes (KEGG) or protein–protein interaction (PPI) networks, under the assumption that genes genetically interacting with a certain mutated gene are adjacent in the networks. As a result, the initial GIs characterized with CRISPR and RNAi screenings were refined to 65 and 23 GIs based on KEGG networks and to 183 and 142 GIs based on PPI networks. The evaluation of refined GIs showed improved precision with respect to known synthetic lethal interactions. The refining process also yielded a synthetic partner network (SPN) for each mutated gene, which provides insight into therapeutic strategies for the mutated genes; specifically, exploring the SPN of mutated BRAF revealed ELAVL1 as a potential target for treating BRAF-mutated cancer, as validated by previous research. We expect that this work will advance cancer therapeutic research.