Pharmaceutical Materials Science Research Articles

Diels-Alder reaction in hydrogel synthesis: Mechanisms and functional aspects.

The Diels-Alder reaction, a classical (4+2) cycloaddition process, holds significant standing within the realms of organic synthesis and polymer chemistry, frequently employed in areas such as pharmaceutical production and material science. Recently, hydrogels constructed via Diels-Alder reactions have garnered considerable attention from researchers. This review aims to summarize the advancements in utilizing the Diels-Alder reaction for hydrogel synthesis, exploring its impact on structural design, functionalization, and application domains. Initially, the fundamental principles of the Diels-Alder reaction are introduced alongside an examination of its benefits and characteristics in hydrogel fabrication. Subsequently, applications of Diels-Alder-generated hydrogels in biomedicine, smart responsive materials, drug delivery systems, among other fields, are comprehensively reviewed. Challenges and limitations encountered during hydrogel synthesis using this reaction are also discussed. Finally, prospective research directions and future prospects of Diels-Alder reactions in hydrogel synthesis are contemplated.

Synthesis of α,α-Difluoromethylene Amines from Thioamides Using Silver Fluoride.

We developed a mild, rapid process employing AgF and thioamides to produce α,α-difluoromethylene amines efficiently. This method exhibited remarkable tolerance toward various functional groups present in N-sulfonylthioamides, thereby broadening the scope of difluoromethylene sulfonamides through a straightforward approach. Additionally, we applied this approach to synthesize various perfluoroalkyl amines, establishing practical synthetic routes for exploring these compounds in pharmaceutical chemistry and materials science.

Skeletal Reorganization: Approaches towards the Synthesis of Aza-Heterocyclic Cores

AbstractThe impetuous development of the pharmaceutical industry and material science stimulates the search for new synthetic approaches and new methods for the synthesis and functionalization of aza-heterocycles; these are some of the key objectives of modern organic chemistry. As a result, an advanced method towards the synthesis of functionalized N-heterocycles that circumvents the limitations associated with traditional methods needs to be devised. In recent decades, rearrangement/reorganization reactions have emerged as a powerful tool for the efficient synthesis of the aza-heterocycle. In this illustration, we summarize some our recent efforts in the development of few complex aza-heterocyclic cores.1 Introduction2 Skeletal Rearrangement of Small Heterocycles via Domino Ring-Opening and Ring-Closing (DROC) Strategy3 Ru(II)-Catalyzed Skeletal Rearrangement of the Quinazoline Ring4 Lewis Acid Catalyzed Skeletal Rearrangement of Furans to Indolizine Cores5 Skeletal Rearrangement of Donor–Acceptor Cyclopropanes via Domino Ring-Opening and Ring-Closing (DROC) Strategy6 Lewis Acid Mediated Skeletal Rearrangement of Donor–Acceptor Spirocyclopropylpyrazolones7 Skeletal Rearrangement through Ring Distortion Strategy8 Conclusion

Ni/Cu Dual-Catalyzed Propargylation for the Stereodivergent Synthesis of Methohexital.

The development of efficient methodologies for the controlled manufacture of specific stereoisomers bearing quaternary stereocenters has prompted advances in a variety of scientific disciplines including pharmaceutical chemistry, materials science, and chemical biology. However, complete control of the absolute and relative stereochemical configurations of alkyne derivatives remains an unmet synthetic challenge. Herein, a Ni/Cu dual-catalyzed asymmetric propargylic substitution reaction is presented to produce propargylated products with all-carbon quaternary stereocenters in high yields with significant diastereo- and enantioselectivities (up to >20:1 dr, >99% ee). The synthesis of all stereochemical variants of methohexital, a widely used sedative-hypnotic drug, exemplifies the efficacy of dual-catalyzed stereodivergent propargylation.

Tabasheer : A Comprehensive Study of Traditional Uses, Phytochemical, Biochemical and Medicinal properties of Tabasheer in Different Varieties of Bamboo

Tabasheer also known as "Bamboo Manna" is a unique substance that has been used in traditional medicine and various industries for centuries. This review paper provides a comprehensive review of Tabasheer including it's a sources chemical composition and potential applications. The paper aims consolidated the existing knowledge on Tabasheer and shed light on its significance in various fields including Pharmaceutical cosmetic and Material Science. Additionally this review discusses the challenges and further properties associated with Tabasheer.

Photochemical Synthesis of Chiral Heterocycles via Asymmetric Carbon‐Heteroatom Bond Formation

AbstractChiral heterocyclic compounds play a crucial role in the pharmaceutical science, materials science, and agrochemical industries. The critical step for synthesizing chiral heterocycles is the formation of asymmetric carbon‐heteroatom bonds, which can be achieved in a chiral environment under thermal or photochemical conditions. However, photochemical asymmetric transformation has become an area of immense growth in the past 15 years. In the drug discovery and development era, chiral photochemical transformations have drawn the attention of researchers to develop new synthetic strategies for chiral heterocycles via asymmetric carbon‐heteroatom bond formation. Chiral photochemistry in the pathway of asymmetric synthesis requires a chirality source which is transferred to the products. A catalytic chiral metal complexing agent or a chiral photosensitizer that generally follows a single electron transfer (SET) or oxidative and reductive quenching cycle has been widely exploited to achieve this goal. In this review, we have demonstrated the recent development of photochemical synthesis of chiral heterocycles via asymmetric carbon‐heteroatom bond formation by using a chiral metal catalyst, asymmetric organocatalyst, or dual catalytic system based on their plausible mechanism.

C-H functionalization enabled by multiple isocyanides.

Past decades have witnessed significant advance of isocyanides as a class of versatile organic synthons as well as their broad applications in multi-component reactions (MCRs) and other tandem reactions. Reactions involving multiple isocyanides allow the construction of molecules with further diversification and complexity, while C-H functionalization emphasizes the advantages of high atom economy, broad substrate availability and great synthetic efficiency. This promising synergistic strategy of C-H functionalization involving multiple isocyanides provides a variety of valuable synthetic methods for organic chemists' toolbox and offers considerable potential in pharmaceutical chemistry and materials science as well. The present review outlines in detail various reaction types of C-H functionalization enabled by multiple isocyanides, and the relevant mechanistic rationale is discussed.

Recent advances in [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species for the synthesis of eight-membered heterocycles.

Numerous eight-membered heterocycles are of significance in biological chemistry, the pharmaceutical industry, agrochemistry, and materials science. However, the assembly of eight-membered heterocycles is usually challenging due to the unfavorable enthalpic and entropic barriers of the transition states during the ring formation. Tremendous efforts have been devoted to the development of synthetic routes to eight-membered heterocycles. Despite these developments, the exploration of more strategies for the facile and effective assembly of eight-membered heterocyclic molecules in a single vessel under mild conditions is still highly desirable. The conjugated heterodiene-participating [4 + 4] annulation serves as a convenient and robust strategy for the synthesis of eight-membered heterocycles from easily accessible starting materials. In recent years, great progress has been achieved in this attractive field. In this short review, we highlighted the recent advances in the synthesis of eight-membered heterocycles via cascade reactions based on [4 + 4] annulation of conjugated heterodienes with 1,4-dipolar species. The brief backgrounds, the general reactions, the proposed mechanisms and their features are summarized. The prospects and challenges of this field are also outlined at the end of this review. In addition, to highlight the importance and practicality of these reactions, the properties of several series of eight-membered heterocycles have also been introduced briefly.

Transition-metal and base-free ether synthesis via alcohol-participated yne-allylic substitution

Ethers are among the most important chemicals in organic synthesis, the pharmaceutical industry, agrochemical production, and material science. C–O bond formation via substitution is one of the most widely used strategies for ether formation. However, known methods usually employ transition-metal and bases to facilitate the process. In this work, we describe the base- and transition-metal-free ether formation via alcohol and phenol-participated substitution. The protocol allows access to a large number of ethers with enyne functional moieties, and features mild reaction conditions, high efficiency, and good regio- and stereoselectivities. The reaction could be readily scaled up, and the products could be used in a range of further transformations.

PolyVinyl alcohol and copper nickel co‐doped titania nanocomposite: Designing, characterization, optical properties, and catalytic application in the synthesis of aryl derivatives of benzothiazole and benzimidazole

The paper examines the properties and potential applications of a nanocomposite material composed of polyvinyl alcohol (PVA) and copper nickel co‐doped titanium dioxide (Cu‐TiO2‐Ni). The material was synthesized using a simple precipitation process, and its properties were characterized using various analytical techniques, including powder X‐ray diffraction, Fourier transform infrared spectroscopy, thermogravimetry analysis, field emission scanning electron microscopy, and high‐resolution tunnelling electron microscopy; Brunauer–Emmett–Teller (BET) surface area was investigated. The results showed that the addition of Cu‐TiO2‐Ni to PVA improved the material's Ultraviolet–visible spectroscopy (UV) absorption properties. Additionally, the PVA/Cu‐TiO2‐Ni nanocomposite material exhibited potential for use in a range of applications, including catalysis. Its utility in synthesizing aryl derivatives of benzothiazole and benzimidazoles, which are crucial intermediates in the fine chemical, agrochemical, and pharmaceutical industries and material science, was evaluated. It was found to offer several advantages, including a quick reaction time, simple workup, and good to excellent isolated yields. These characteristics make this protocol both practical and economically intriguing.

One-step synthesis of perfluorinated polyphenylenes using modified Ullmann coupling conditions

Fluorinated compounds have attracted attention in both the pharmaceutical industry and materials science due to the small size and strong electron-withdrawing property of the fluorine atom. In materials science, perfluorinated polyphenylenes play an important role as electron transport layers in organic electronics. While various strategies for the preparation of fluorinated arenes have been reported, the number of synthetic methods available for perfluorinated arenes remains limited, mainly due to the change in reactivity of reagents and substrates at the reaction site upon the introduction of additional fluorine atoms. Given the important applications of perfluorinated polyphenyl-based compounds, this article describes the one-step synthesis of the dendrimer perfluoro-3,3’5,5’-tetrakisphenyldiphenyl-1,1’, which to date no example of a targeted synthesis has been reported in literature, and the synthetic methodology for the direct preparation of linear perfluorinated para-sexiphenyl. Both strategies use starting materials that are either commercially available or can be easily accessed using standard literature methods.

Synthesis of 1-perfluoroalkyl-3-heteroaryl bicyclo[1.1.1]pentanes via visible light-induced and metal-free perfluoroalkylation of [1.1.1]propellane

Visible light-induced perfluoroalkylation of [1.1.1]propellane provides a sustainable way to incorporate perfluoroalkyl-substituted BCPs into various heterocycles.

Quantitative definition of chemical synthetic pathway complexity of organic compounds

Irrespective of the final application of a molecule, synthetic accessibility is the rate-determining step in discovering and developing novel entities. However, synthetic complexity is challenging to quantify as a single metric, since it is a composite of several measurable metrics, some of which include cost, safety, and availability. Moreover, defining a single synthetic accessibility metric for both natural products and non-natural products poses yet another challenge given the structural distinctions between these two classes of compounds. Here, we propose a model for synthetic accessibility of all chemical compounds, inspired by the Central Limit Theorem, and devise a novel synthetic accessibility metric assessing the overall feasibility of making chemical compounds that has been fitted to a Gaussian distribution. Our approach utilizes a Gaussian mixture model (GMM) and Autoencoder, which rank synthetic complexity for natural products. This model can inform total synthesis of natural products, process chemistry in pharmaceutical contexts, materials science, and chemical engineering. Based on our findings, we conclude that the Autoencoder model is better suited to model the true probability distribution of synthetic complexity for natural products.

Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds

Selective deuteration of unactivated C(sp3)-H bonds is a highly attractive but challenging subject of research in pharmaceutical chemistry, material science and synthetic chemistry. Reported herein is a practical, highly selective and economical efficient hydrogen/deuterium (H/D) exchange of unactivated C(sp3)-H bonds by synergistic photocatalysis and hydrogen atom transfer (HAT) catalysis. With the easily prepared PMP-substituted amides as nitrogen-centered radical precursors, a wide range of structurally diverse amides can undergo predictable radical H/D exchange smoothly with inexpensive D2O as the sole deuterium source, giving rise to the distal tertiary, secondary and primary C(sp3)-H bonds selectively deuterated products in yields of up to 99% and excellent D-incorporations. In addition to precise monodeuteration, this strategy can also achieve multideuteration of the substrates contain more than one remote C(sp3)-H bond, which opens a method to address multi-functionalization of distal unactivated C(sp3)–H bonds.

Radical deuteration.

Deuterated chemicals are becoming irreplaceable in pharmaceutical engineering, material science and synthetic chemistry. Many excellent reviews have discussed acid/base-dependent or metal-catalyzed deuteration reactions, but radical deuterations have been discussed less. With the development of radical chemistry, there has been a rapid growth in radical deuterium-labelling technology. Diverse mild, cheap and efficient strategies for deuterium atom installation have been reported, and this review summarizes the recent achievements of radical deuteration classified by the reaction types.

“Thiol-free synthesized” and sustainable thiolating synthons for nickel-catalyzed reductive assembly of sulfides with high efficiency

Unsymmetrical sulfides are widely found in the pharmaceutical industry, organic synthesis, and materials science.

Intermolecular Diels-Alder Cycloadditions of Furfural-Based Chemicals from Renewable Resources: A Focus on the Regio- and Diastereoselectivity in the Reaction with Alkenes.

A recent strong trend toward green and sustainable chemistry has promoted the intensive use of renewable carbon sources for the production of polymers, biofuels, chemicals, monomers and other valuable products. The Diels-Alder reaction is of great importance in the chemistry of renewable resources and provides an atom-economic pathway for fine chemical synthesis and for the production of materials. The biobased furans furfural and 5-(hydroxymethyl)furfural, which can be easily obtained from the carbohydrate part of plant biomass, were recognized as “platform chemicals” that will help to replace the existing oil-based refining to biorefining. Diels-Alder cycloaddition of furanic dienes with various dienophiles represents the ideal example of a “green” process characterized by a 100% atom economy and a reasonable E-factor. In this review, we first summarize the literature data on the regio- and diastereoselectivity of intermolecular Diels-Alder reactions of furfural derivatives with alkenes with the aim of establishing the current progress in the efficient production of practically important low-molecular-weight products. The information provided here will be useful and relevant to scientists in many fields, including medical and pharmaceutical research, polymer development and materials science.

Recent Advances in Late-Stage Construction of Stapled Peptides via C-H Activation.

Stapled peptides have been widely applied in many fields, including pharmaceutical chemistry, diagnostic reagents, and materials science. However, most traditional stapled peptide preparation methods rely on prefunctionalizations, which limit the diversity of stapled peptides. Recently, the emergence of late-stage transition metal-catalyzed C-H activation in amino acids and peptides has attracted wide interest due to its robustness and applicability for peptide stapling. In this review, we summarize the methods for late-stage construction of stapled peptides via transition metal-catalyzed C-H activation.

Implementation of Diverse Synthetic and Strategic Approaches to Biologically Active Sulfamides

AbstractSulfamide compounds are an important class of motif in various applications in pharmaceutical agents, agriculture, and material science. In this review, various synthetic strategies toward acyclic and cyclic sulfamide compounds utilizing many different methods are described. Herein, efficient and innovative synthetic methods ranging from small molecules to large rings for bioactive compounds, small molecules, and catalyst development are discussed.

Modeling and Simulation of Process Technology for Nanoparticulate Drug Formulations-A Particle Technology Perspective.

Crystalline organic nanoparticles and their amorphous equivalents (ONP) have the potential to become a next-generation formulation technology for dissolution-rate limited biopharmaceutical classification system (BCS) class IIa molecules if the following requisites are met: (i) a quantitative understanding of the bioavailability enhancement benefit versus established formulation technologies and a reliable track record of successful case studies are available; (ii) efficient experimentation workflows with a minimum amount of active ingredient and a high degree of digitalization via, e.g., automation and computer-based experimentation planning are implemented; (iii) the scalability of the nanoparticle-based oral delivery formulation technology from the lab to manufacturing is ensured. Modeling and simulation approaches informed by the pharmaceutical material science paradigm can help to meet these requisites, especially if the entire value chain from formulation to oral delivery is covered. Any comprehensive digitalization of drug formulation requires combining pharmaceutical materials science with the adequate formulation and process technologies on the one hand and quantitative pharmacokinetics and drug administration dynamics in the human body on the other hand. Models for the technical realization of the drug production and the distribution of the pharmaceutical compound in the human body are coupled via the central objective, namely bioavailability. The underlying challenges can only be addressed by hierarchical approaches for property and process design. The tools for multiscale modeling of the here-considered particle processes (e.g., by coupled computational fluid dynamics, population balance models, Noyes–Whitney dissolution kinetics) and physiologically based absorption modeling are available. Significant advances are being made in enhancing the bioavailability of hydrophobic compounds by applying innovative solutions. As examples, the predictive modeling of anti-solvent precipitation is presented, and options for the model development of comminution processes are discussed.