Advances In Chemical Synthesis Research Articles

Modern approaches to therapeutic oligonucleotide manufacturing.

Therapeutic oligonucleotides are a powerful drug modality with the potential to treat many diseases. The rapidly growing number of therapies that have been approved and that are in advanced clinical trials will place unprecedented demands on our capacity to manufacture oligonucleotides at scale. Existing methods based on solid-phase phosphoramidite chemistry are limited by their scalability and sustainability, and new approaches are urgently needed to deliver the multiton quantities of oligonucleotides that are required for therapeutic applications. The chemistry community has risen to the challenge by rethinking strategies for oligonucleotide production. Advances in chemical synthesis, biocatalysis, and process engineering technologies are leading to increasingly efficient and selective routes to oligonucleotide sequences. We review these developments, along with remaining challenges and opportunities for innovations that will allow the sustainable manufacture of diverse oligonucleotide products.

Synthesis of Modified C-Nucleosides of Therapeutic Significant: A Succinct Account

AbstractSince their discovery in the 1950s, C-nucleosides have piqued the interest of both biologists and medicinal chemists. In this regard, C-nucleosides and their synthetic analogues have resulted in promising leads in drug design. Concurrently, advances in chemical syntheses have contributed to structural diversity and drug discovery efforts. Convergent and modular approaches to synthesis have gained much attention in this regard. Among them nucleophilic substitution at C-1 has seen wide applications, providing flexibility in synthesis, good yields, the ability to maneuver stereochemistry as well as to incorporate structural modifications. In this account, we briefly discuss the modular synthesis of C-nucleosides with a focus on mechanistic studies and sugar modifications that have resulted in potent lead molecules. Meanwhile, various FDA-approved C-nucleoside analogues have been reported previously for their antiviral and/or anticancer potential, with examples being pyrazomycin, remdesivir, pseudouridine, and pseudouridimycin.1 Introduction and Motivation2 Strategies for the Synthesis of C-Nucleosides3 Biologically Active C-Nucleosides4 Mechanistic Analysis of C-Nucleoside Formation5 Synthesis and Manipulation of Medicinally Important C-Nucleoside Analogues6 C-Nucleosides: Synthesis of C–C Bonds with a C-1′ Base7 Conclusion

Recent Advances in Chemical Synthesis of Structural Domains of Lipopolysaccharides from the Commensal Gut-Associated Microbiota.

Lipopolysaccharides from the commensal gut-associated microbiota are interesting biomolecules for the treatment of various inflammatory diseases. Different from pathogenic lipopolysaccharides, commensal lipopolysaccharides have distinct chemical structures and mediate beneficial homeostasis with the immune system of the host. However, the accessibility issues of homogenous and pure commensal lipopolysaccharides hampered the in-depth studies of their functions. In this concept article, we highlight the recent synthesis of lipopolysaccharides from gut-associated lymphoid-tissue-resident Alcaligenes faecalis and Bacteroides vulgatus, which hopes to inspire the more efforts devoting to these fantastic biomolecules.

Recent Advances in Chemical Synthesis of Amino Sugars.

Amino sugars are a kind of carbohydrates with one or more hydroxyl groups replaced by an amino group. They play crucial roles in a broad range of biological activities. Over the past few decades, there have been continuing efforts on the stereoselective glycosylation of amino sugars. However, the introduction of glycoside bearing basic nitrogen is challenging using conventional Lewis acid-promoted pathways owing to competitive coordination of the amine to the Lewis acid promoter. Additionally, diastereomeric mixtures of O-glycoside are often produced if aminoglycoside lack a C2 substituent. This review focuses on the updated overview of the way to stereoselective synthesis of 1,2-cis-aminoglycoside. The scope, mechanism, and the applications in the synthesis of complex glycoconjugates for the representative methodologies were also included.

Oral delivery of nucleic acid therapeutics: Challenges, strategies, and opportunities.

In recent decades, advances in chemical synthesis and delivery systems have accelerated the development of therapeutic nucleic acids, several of which have been approved by the Us Food and Drug Administration (FDA). Oral nucleic acid delivery is preferred because of its simplicity and patient compliance, but it still presents distinct challenges. The negative charge, hydrophilicity, and large molecular weight of nucleic acids combined with in vivo gastrointestinal (GI) barriers (e.g., acidic pH, enzymes, mucus, and intestinal epithelial cells) severely hinder their delivery efficacy. Recently, various nanoparticles (NPs), ranging from polymeric to lipid-based (L)NPs and extracellular vesicles (EVs), have been extensively explored to address these obstacles. In this review, we describe the physiological barriers in the GI tract and summarize recent advances in NP-based oral nucleic acid therapeutics.

Self-Assembly of Repetitive Segment and Random Segment Polymer Architectures.

Recent advances in chemical synthesis have created new methodologies for synthesizing sequence-controlled synthetic polymers, but rational design of monomer sequence for desired properties remains challenging. In this work, we synthesize periodic polymers with repetitive segments using a sequence-controlled ring-opening metathesis polymerization (ROMP) method, which draws inspiration from proteins containing repetitive sequence motifs. The repetitive segment architecture is shown to dramatically affect the self-assembly behavior of these materials. Our results show that polymers with identical repetitive sequences assemble into uniform spherical nanoparticles after thermal annealing, whereas copolymers with random placement of segments with different sequences exhibit disordered assemblies without a well-defined morphology. Overall, these results bring a new understanding to the role of periodic repetitive sequences in polymer assembly.

Phosphazene Cyclomatrix Network-Based Polymer: Chemistry, Synthesis, and Applications.

Polyphosphazenes are an inorganic molecular hybrid family with multifunctional properties due to their wide range of organic substitutes. This review intends to propose the basics of the synthetic chemistry of polyphosphazene, describing for researchers outside the field the basic knowledge required to design and prepare polyphosphazenes with desired properties. A special emphasis is placed on recent advances in chemical synthesis, which allow not only the synthesis of polyphosphazenes with controlled molecular weights and polydispersities but also the synthesis of novel branched designs and block copolymers. We also investigated the synthesis of polyphosphazenes using various functional materials. This review aims to assist researchers in synthesizing their specific polyphosphazene material with unique property combinations, with the hope of stimulating further research and even more innovative applications for these highly interesting multifaceted materials.

Production of bioflocculants from spent brewer's yeast and its application in the treatment of effluents with textile dyes

Advances in chemical synthesis have increased the complexity and degradation resistance of dyes used in textile processes. This fact interferes drastically with conventional biological wastewater treatment and demands further methods to avoid environmental damage. In this sense, this work presents a bioflocculant produced by the alkaline hydrolysis of spent brewer's yeast, a residue from the brewing industry, as well as the evaluation of its performance in the precipitation of recalcitrant dyes. The optimum hydrolysis system was accessed by a full 23 factorial design in terms of NaOH concentration, yeast mass, and temperature, followed by a kinetic study. The solid fraction composition of the produced flocculant agent is 46 % of proteins and 29 % of polysaccharides. The performance of the bioflocculant was evaluated in two different systems, real textile wastewater containing rhodamine and a synthetic solution with flavine. The effects of the flocculation variables pH, temperature, agitation, and flocculant agent dosage were taken into consideration. Color removal outcomes above 80 and 90 % were attained for rhodamine and flavine systems, respectively. Further analysis of real textile wastewater for treated and untreated samples in terms of BOD, COD, TOC, and light metals was performed. A biodegradability test showed the employed treatment could increase microbial assimilation of the sample and reduce its persistent compounds. This work shows, for the first time, the feasibility of the bioflocculant from spent brewer's yeast and features its potential applicability to recalcitrant compounds precipitation in textile wastewaters.

Molecular dynamics simulations reveal statistics and microscopic mechanisms of water permeation in membrane-embedded artificial water channel nanoconstructs.

Understanding water transport mechanisms at the nanoscale level remains a challenge for theoretical chemical physics. Major advances in chemical synthesis have allowed us to discover new artificial water channels, rivaling with or even surpassing water conductance and selectivity of natural protein channels. In order to interpret experimental features and understand microscopic determinants for performance improvements, numerical approaches based on all-atom molecular dynamics simulations and enhanced sampling methods have been proposed. In this study, we quantify the influence of microscopic observables, such as channel radius and hydrogen bond connectivity, and of meso-scale features, such as the size of self-assembly blocks, on the permeation rate of a self-assembled nanocrystal-like artificial water channel. Although the absolute permeation rate extrapolated from these simulations is overestimated by one order of magnitude compared to the experimental measurement, the detailed analysis of several observed conductive patterns in large assemblies opens new pathways to scalable membranes with enhanced water conductance for the future design.

Change the channel: CysLoop receptor antagonists from nature.

Vertebrate and invertebrate ligand-gated ion channels (LGICs) exhibit significant structural homology and often share ligands. As a result, ligands with activity against one class can be brought to bear against another, including for development as insecticides. Receptor selectivity, metabolism and distribution must then be optimized using chemical synthesis. Here we review natural products (NPs) that ligate and inhibit the Cys-loop family of LGICs, which benefit from the unique physicochemical properties of natural product space but often present a high synthetic burden. Recent advances in chemical synthesis, however, have opened practical entries into these complex structures, several of which are highlighted. © 2020 Society of Chemical Industry.

Shedding Light on the Role of Misfit Strain in Controlling Core-Shell Nanocrystals.

Heteroepitaxial modification of nanomaterials has become a powerful means to create novel functionalities for various applications. One of the most elementary factors in heteroepitaxial nanostructures is the misfit strain arising from mismatched lattices of the constituent parts. Misfit strain not only dictates epitaxy kinetics for diversifying nanocrystal morphologies but also provides rational control over materials properties. In recent years, advances in chemical synthesis along with the rapid development of electron microscopy and X-ray diffraction techniques have enabled a substantial understanding of strain-related processes, which offers theoretical foundation and experimental guidance for researchers to refine heteroepitaxial nanostructures and their properties. Herein, recent investigations on heterogeneous core-shell nanocrystals containing misfit strains are summarized, with a focus on the mechanistic understanding of strain and strain-induced effects such as tuning the epitaxial habit, modulating the optical emission, and enhancing the catalytic activity and magnetic coercivity.

Quantitative Understanding of Superparamagnetic Blocking in Thoroughly Characterized Ni Nanoparticle Assemblies

Thanks to advances in chemical synthesis that enable control over the size, structure, properties, and functionalization, magnetic nanoparticles (NPs) present unique opportunities in areas as diver...

Tools and Incentives for Implementing Codes of Ethics to Help Prevent the Reemergence of Chemical Weapons

Since 1997, when the Chemical Weapons Convention (CWC) entered into force and the Organisation for Prohibition of Chemical Weapons (OPCW) was established, >97% of the world’s declared stockpile, comprising 70,372 t of chemical warfare agents, has been destroyed. Despite this notable progress, advances in chemical synthesis bring new challenges to preventing chemical weapons production. The development of ethical codes or guidelines such as The Hague Ethical Guidelines and the Global Chemists’ Code of Ethics (GCCE) and their voluntary adoption by chemical practitioners worldwide are important steps in strengthening international nonproliferation efforts through their potential to impact the intent of the individual by normalizing ethical behavior. However, the simple act of adopting a code or implementing Responsible Care initiatives does not guarantee ethical behavior. Individuals’ decisions often contribute to the seriousness of chemical incidents and accidents, even if the root causes are shortfalls in safety and/or security. History is replete with accounts of chemical incidents that were made worse due to ethics failures at the individual and/or corporate level. The cost associated with response and root cause investigations for such incidents can be massive, but knee-jerk reactions to push for more regulation or to establish more oversight mechanisms following the immediate impact and initial cleanup may require significantly more resources to execute. At their core, ethics failures often arise, at least partially, due to a lack of shared investment in the company’s mission. When people are guided by a shared mission, they are more likely to bring a sense of professionalism to their work and to hold each other accountable for ethical behavior. Scenario-based training can provide new employees opportunities to practice acting ethically, but it takes time and money to organize in-person training events. Careful implementation of scenario-based e-learning to teach behavioral expectations that compel trainees to practice and discuss ethics, however, can provide a meaningful way to ensure employees are provided the necessary opportunities to rehearse ethical behavior, regardless of where they are physically located. As individuals become comfortable identifying and standing up for what is right, they strengthen their resolve to act when issues arise in the future. Company managers and university professors alike have a duty to educate others on the importance of ethical behavior, capitalize on teachable moments to help others understand the principles behind the desired behaviors, encourage others to speak up and act when they see something wrong, and model the behaviors they seek. In so doing, they may actively participate in making the world a better place and minimize the potential for the reemergence of chemical weapons.

Recent Advances in Chemical Synthesis of Polysaccharides

Recent Advances in Chemical Synthesis of Polysaccharides

Recent Advance in Near‐Infrared (NIR) Imaging Probes for Cancer Theranostics

AbstractWith the advantages of low biofluid scattering and minimal absorbance, light in a second near‐infrared window (NIR II, 1000–1700 nm) either as a signal or as an excitation source is preferred for bioimaging and disease diagnosis, especially for cancer theranostics. Due to recent advances in chemical synthesis and imaging techniques, various NIR II probes have been evaluated for tumor luminescence image‐guided cancer therapy and surgery. Furthermore, probes emitting optical, acoustic, or thermal signals under NIR II excitation have also been developed for upconversion luminescence, photoacoustic, and photothermal imaging of tumors. Herein, recent advances in the use of NIR II imaging probes in cancer theranostic applications are summarized along with future perspectives.

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides.

C-nucleosides have intrigued biologists and medicinal chemists since their discovery in 1950's. In that regard, C-nucleosides and their synthetic analogues have resulted in promising leads in drug design. Concurrently, advances in chemical syntheses have contributed to structural diversity and drug discovery efforts. Convergent and modular approaches to synthesis have garnered much attention in this regard. Among them nucleophilic substitution at C1' has seen wide applications providing flexibility in synthesis, good yields, the ability to maneuver stereochemistry as well as to incorporate structural modifications. In this review, we describe recent reports on the modular synthesis of C-nucleosides with a focus on D-ribonolactone and sugar modifications that have resulted in potent lead molecules.

The Human Milk Glycome as a Defense Against Infectious Diseases: Rationale, Challenges, and Opportunities.

Each year over 3 million people die from infectious diseases with most of these deaths being poor and young children who live in low- and middle-income countries. Infectious diseases emerge for a multitude of reasons. On the social front, reasons include a breakdown of public health standards, international travel, and immigration (for financial, civil, and social reasons). At the molecular level, the modern rise of infectious diseases is tied to the juxtaposition of drug-resistant pathogens and a lack of new antimicrobials. The consequence is the possibility that humankind will return to the preantibiotic era wherein millions of people will perish from what should be trivial illnesses. Given the stakes, it is imperative that the chemistry community take leadership in delivering new antibiotic leads for clinical development. We believe this can happen through innovation in two areas. First is the development of novel chemical scaffolds to treat infections caused by multidrug-resistant pathogens. The second area, which is not exclusive to the first, is the generation of antibiotics that do not cause collateral damage to the host or the host's microbiome. Both can be enabled through advances in chemical synthesis. It is with this general philosophy in mind that we hypothesized human milk oligosaccharides (HMOs) could serve as novel chemical scaffolds for antibacterial development. We provide herein a personal account of our laboratory's progress toward the goal of using HMOs as a defense against infectious diseases.

Controlling Molecular Doping in Organic Semiconductors.

The field of organic electronics thrives on the hope of enabling low-cost, solution-processed electronic devices with mechanical, optoelectronic, and chemical properties not available from inorganic semiconductors. A key to the success of these aspirations is the ability to controllably dope organic semiconductors with high spatial resolution. Here, recent progress in molecular doping of organic semiconductors is summarized, with an emphasis on solution-processed p-type doped polymeric semiconductors. Highlighted topics include how solution-processing techniques can control the distribution, diffusion, and density of dopants within the organic semiconductor, and, in turn, affect the electronic properties of the material. Research in these areas has recently intensified, thanks to advances in chemical synthesis, improved understanding of charged states in organic materials, and a focus on relating fabrication techniques to morphology. Significant disorder in these systems, along with complex interactions between doping and film morphology, is often responsible for charge trapping and low doping efficiency. However, the strong coupling between doping, solubility, and morphology can be harnessed to control crystallinity, create doping gradients, and pattern polymers. These breakthroughs suggest a role for molecular doping not only in device function but also in fabrication-applications beyond those directly analogous to inorganic doping.

A Stereocontrolled Annulation of the Taccalonolide Epoxy Lactone onto the Molecular Framework of trans-Androsterone.

A robust and scalable route to the taccalonolide skeleton starting from trans-androsterone is presented. The synthesis features a cyclic hydroboration carbonylation reaction, which effectively establishes the trans-hydrindane DE ring junction in a remarkable annulation reaction, as well as a Claisen rearrangement and a catalytic Ullmann-type cyclization. This work is part of a larger effort to uncover new clinical candidates from the taccalonolide class of anticancer agents through advances in chemical synthesis.

Exchange Bias Effects in Iron Oxide-Based Nanoparticle Systems.

The exploration of exchange bias (EB) on the nanoscale provides a novel approach to improving the anisotropic properties of magnetic nanoparticles for prospective applications in nanospintronics and nanomedicine. However, the physical origin of EB is not fully understood. Recent advances in chemical synthesis provide a unique opportunity to explore EB in a variety of iron oxide-based nanostructures ranging from core/shell to hollow and hybrid composite nanoparticles. Experimental and atomistic Monte Carlo studies have shed light on the roles of interface and surface spins in these nanosystems. This review paper aims to provide a thorough understanding of the EB and related phenomena in iron oxide-based nanoparticle systems, knowledge of which is essential to tune the anisotropic magnetic properties of exchange-coupled nanoparticle systems for potential applications.