Practical Synthesis Research Articles

Recent Advancements in Continuous-Flow Suzuki-Miyaura Coupling Utilizing Immobilized Molecular Palladium Complexes.

Immobilized Pd-catalyzed Suzuki-Miyaura coupling under continuous-flow conditions using a packed-bed reactor, representing an efficient, automated, practical, and safe technology compared to conventional batch-type reactions. The core objective of this study is the development of an active and durable catalyst. In contrast to supported Pd nanoparticles, the attachment of Pd complexes onto solid supports through well-defined coordination sites is considered a favorable approach for preparing highly dispersed and stabilized Pd species. These species can be directly employed in various flow reactions without the need for pre-treatment. This concept paper explores recent achievements involving the application of immobilized Pd complexes as precatalysts for continuous-flow Suzuki-Miyaura coupling. Our focus is to elucidate the significance of the designed catalyst structures in relation to their catalytic performance under flow conditions. Additionally, we highlight various reaction systems and catalyst packing methods, emphasizing their crucial roles in establishing a practical synthesis process.

Practical and Selective Syntheses of S‐Acyl and N‐Acyl Glutathiones with N‐Acyl Imidazoles in Water

AbstractA selective, mild, convenient, and green protocol for the preparation of S‐acyl and N‐acyl glutathiones is described involving the chemical modification of glutathione (GSH) with N‐acyl imidazoles at room temperature in water. The syntheses of S‐acyl glutathiones were achieved in very high yields using 1 equiv. of an N‐acyl imidazole in water at room temperature, without the need of a base. Double acylation of GSH with various N‐acyl imidazoles in weakly basic aqueous media in the presence of N‐hydroxysuccinimide (HOSu) as the activating reagent followed by selective deprotection of the S‐acyl group with aqueous ammonia at room temperature gave high yields of N‐acyl glutathiones. Moreover, the reaction could accommodate a diverse range of carboxylic acids such as (hetero)benzoic acids, phenylacetic acids, aliphatic acids from short‐chain fatty acids (including acetic acid), long‐chain polyunsaturated fatty acids, secondary or tertiary amino acids, and carboxylic acids containing clickable functional groups, fluorescent probes, or drugs.

Innovative forestry: a synthesis of small-scale forest management practice from Nepal

This guidebook has been published at a time when there is a widespread recognition in Nepal that community forests are not beingactively managed to realize their full potential. Whilst there are both institutional and technical solutions to this problem, the guidebook has clearly spelled out its position in addressing the technical issues of forest management in a way field workers can really understand and articulate while working with forest user groups.

Stereocontrolled Synthesis of a Heptose- and Kdo-Containing Common Inner Core Trisaccharide of Lipopolysaccharides from Multiple Pathogenic Bacteria

Lipopolysaccharide (LPS) is a major virulence determinant in Gram-negative bacteria and responsible for many pathophysiological processes during bacterial infections. However, the accessibility of LPS-associated oligosaccharides for infectious mechanism study and vaccine development remains challenging. Herein, we report an efficiently stereocontrolled approach for synthesis of a common inner core trisaccharide containing difficult-to-access rare higher-carbon sugars heptose (Hep) and 3-deoxy-α-D-manno-oct-2-ulosonic acid (Kdo). Key features include comprehensive elaboration of practical synthesis of versatile Hep and Kdo building blocks and stereoselective assembly of an inner core trisaccharide from multiple pathogenic bacteria.

Vadim Petrovsky: “Berne Himself Left Injunctions Against Empirical Research to His Successors, and It’s Time for Us to Circumvent These Injunctions”

Interview with Vadim Arturovich Petrovsky, Doctor of Psychological Sciences, Professor, Corresponding member of the Russian Academy of Education, psychologist in the modality of transactional analysis, about the synthesis of psychological practice and scientific research in the field of psychology in general and transactional analysis in particular. In this interview, issues such as the willingness of practicing psychologists of the transactional analysis modality to conduct their own research and scientific experiments are raised, the difficulties of modern psychological science, the connection and interpenetration of the practice and theory of transactional analysis are discussed. The interview also talks about the objective limitations of transactional analysis as a scientific method and the subjective characteristics of practicing psychologists in terms of writing scientific articles and conducting research. The conversation between the editor-in-chief of the journal “Transactional Analysis in Russia” and Vadim Petrovsky touched upon unexplored topics and areas of development of TA and its concepts as objects of scientific research for the psychological community not only in Russia, but also in the world. Which fields (Counseling, Psychotherapy, Education, TA in Organisations) and concepts of Transactional Analysis are most ready today to bridge the gap from practice to theory and vice versa?

KHSO4 promoted practical synthesis of quinazolin-4(3H)-ones and benzothiadiazine 1,1-dioxides

A broad scope of quinazolin-4(3H)-ones or benzothiadiazine 1,1-dioxides was obtained via a transition-metal free and convenient method. This approach involving KHSO4 promoted cyclization and dehydration between diverse functionalized 2-aminobenzamides or 2-aminobenzenesulfonamides and N, N-dimethylformamide derivatives. The protocol offers moderate to excellent yields (45%-93%) under mild condition in a short of reaction time of 6 hours. The use of an environment-friendly and less expensive catalyst KHSO4 also makes this protocol more attractive.

A practical chemical synthesis of avicholic acid

A 10-step synthesis of the unique C16-hydroxylated bile acid natural product avicholic acid from cheap, industrial material dehydroepiandrosterone (DHEA) is reported. This synthesis features an improved four-step sequence for the construction of the known 3α,7α-dihydroxy-5β-androstan-17-one, and a practical installation of C16α-OH through the key functionalization on ring D via an easy and efficient ene reaction, which enables a gram-scale preparation of avicholic acid in only 10 steps and with 16 % overall yield.

Practical synthesis of (S)‐pyroglutamic acid

AbstractA simple and rapid synthesis of (S)‐pyroglutamic acid was developed by the thermal cyclodehydration of (S)‐glutamic acid under solvent‐free conditions, with continuous swirling during heating (220°C) to ensure homogeneity of the melt. The reaction proceeds until the bubbles disappear, not exceeding 5 min. The heating immediately ceases, then cooling the reaction vessel to prevent degradation and racemization. (S)‐pyroglutamic acid is obtained in 70% yield, and the enantiomeric ratio is 97:3. The same reaction under microwave heating in an aqueous solution afforded a low yield of racemic product.

Practical Synthesis of 6-Amino-1-hydroxy-2,1-benzoxaborolane: A Key Intermediate of DNDI-6148.

Visceral leishmaniasis (VL), a parasitic, poverty-linked, neglected disease, is endemic across multiple regions of the world and fatal if untreated. There is an urgent need for a better and more affordable treatment for VL. DNDI-6148 is a promising drug candidate being evaluated for the treatment of VL; however, the current process for producing the key intermediate of DNDI-6148, 6-amino-1-hydroxy-2,1-benzoxaborolane, is expensive and difficult to scale up. Herein, we describe two practical approaches to synthesizing 6-amino-1-hydroxy-2,1-benzoxaborolane from inexpensive and readily available raw materials. Starting with 4-tolunitrile, the first approach is a five-step sequence involving a Hofmann rearrangement, resulting in an overall yield of 40%. The second approach utilizes 2-methyl-5-nitroaniline as the starting material and features borylation of aniline and continuous flow hydrogenation as the key steps, with an overall yield of 46%. Both routes bypass the nitration of 1-hydroxy-2,1-benzoxaborolane, which is challenging and expensive to scale. In particular, the second approach is more practical and scalable because of the mild operating conditions and facile isolation process.

LEVERAGING GENERATIVE AI: STRATEGIC ADOPTION PATTERNS FOR ENTERPRISES

Generative Artificial Intelligence (AI) is a rapidly evolving subset of AI technologies that involves creating new content, such as text, images, and audio, using algorithms trained on large datasets. Well-known examples of generative AI technologies include Generative Adversarial Networks (GANs) and Generative Pre-trained Transformers (GPT). These innovations are increasingly being integrated into various business applications, from automating content creation and enhancing customer interactions to driving product development and innovation. The importance of generative AI in a business context lies in its potential to augment human creativity, improve operational efficiency, and unlock new business opportunities, making it a critical tool for enterprises aiming to maintain a competitive edge in the digital age. Despite its transformational potential, the implementation of generative AI in businesses faces significant challenges. High implementation costs, the complexity of integrating AI systems into existing infrastructures, a shortage of skilled specialists, and ethical issues related to data privacy and AI-generated content are among the primary obstacles. Additionally, businesses often struggle to align AI initiatives with their strategic goals and ensure that AI outputs meet high standards of quality and compliance. These barriers complicate the large-scale and effective adoption of generative AI, limiting its potential to revolutionize business operations and innovation. The research encompasses a comprehensive review of existing literature, analysis of real-world cases, and synthesis of best practices in the strategic implementation of generative AI. It explores strategic models for the deployment of generative AI in enterprises, identifies key drivers and barriers to its adoption in business environments, and examines the strategic approaches businesses use to integrate generative AI into their operations. Insights and recommendations are provided for enterprises considering the adoption of generative AI technologies. The importance of the research lies in its potential to help businesses overcome implementation challenges and maximize the benefits of generative AI. Understanding strategic models and approaches to AI integration will enable businesses to better navigate the complexities of AI deployment, enhance their innovative capabilities, and ensure sustainable growth in an increasingly competitive market. The conclusions drawn from the research aim to bridge the gap between theoretical insights and practical applications of generative AI, providing a valuable resource for business leaders, technology strategists, and policymakers seeking to leverage AI for competitive advantage.

Practical synthesis of epocholeone, a plant growth-promoting steroid with long-lasting activity

The steroidal plant growth-promoting lactone epocholeone has attracted much attention due to its great potential applications in agriculture. Herein, we report a chromatography–free synthesis of the epocholeone using a potassium osmate-catalyzed asymmetric dihydroxylation as the key reaction. Compared to the existing literature routes, the current protocol features low–toxicity reagents, simple operations and mild conditions. We expect this practical synthesis offers a preferred means to produce epocholeone in manufacturing.

Practical liquid phase mixing-calcination synthesis of Nb5+ doped SrTiO3 nanoparticles with elevated photocatalysis

The mediocre photocatalytic activity and unpractical preparation methods of SrTiO3 have restricted its practical application as a photocatalyst. Herein, a practical liquid phase mixing-calcination method was designed to synthesize Nb5+ doped SrTiO3 (Nb-SrTiO3) with remarkably elevated photocatalytic activity. Nb-SrTiO3 nanoparticles were synthesized by mixing Sr(NO3)2, NbCl5 and tetrabutyl titanate in deionized water (DW), evaporating the solvent (DW) and calcining the evenly mixed precursors at 700 °C for 4 h. The as-synthesized Nb-SrTiO3 exhibited a photocatalytic activity 4.2 times that of SrTiO3 in the reduction of Cr(VI) under Xenon lamp irradiation. Moreover, Nb-SrTiO3 showed a rather good photocatalytic stability. Nb5+ doping can decrease the particle size and promote the photogenerated carrier separation and transfer of SrTiO3, thereby contributing to heightened photocatalytic activity of Nb-SrTiO3.

One-pot sustainable synthesis of glucosylglycerate from starch and glycerol through artificial in vitro enzymatic cascade

Glucosylglycerate (R-2-O-α-D-glucopyranosyl-glycerate, GG) is a negatively charged compatible solution with versatile functions. Here, an artificial in vitro enzymatic cascade was designed to feasibly and sustainably produce GG from affordable starch and glycerol. First, Spirochaeta thermophila glucosylglycerate phosphorylase (GGP) was carefully selected because of its excellent heterologous expression, specific activity, and thermostability. The optimized two-enzyme cascade, consisting of alpha-glucan phosphorylase (αGP) and GGP, achieved a remarkable 81 % conversion rate from maltodextrin and D-glycerate. Scaling up this cascade resulted in a practical concentration of 58 g/L GG with a 62 % conversion rate based on the added D-glycerate. Additionally, the production of GG from inexpensive starch and glycerol in one-pot using artificial four-enzyme cascade was successfully implemented, which integrates alditol oxidase and catalase with αGP and GGP. Collectively, this sustainable enzymatic cascade demonstrates the feasibility of the practical synthesis of GG and has the potential to produce other glycosides using the phosphorylase-and-phosphorylase paradigm.

Synthesis and Spectroscopic Characterization of Selected Water-Soluble Ligands Based on 1,10-Phenanthroline Core.

Water-soluble ligands based on a 1,10-phenanthroline core are relatively poorly studied compounds. Developing efficient and convenient syntheses of them would result in new interesting applications because of the importance of 1,10-phenanthrolines. In this manuscript, we describe novel and practical ways to introduce a carboxyl and, for the first time, a phenol and dithiocarboxyl group under mild reaction conditions. This strategy enables highly efficient and practical synthesis of suitable organosulfur compounds with high added value, high chemoselectivity, and a broad substrate range. We present the selective conversion of a hydroxydialdehyde in the form of 10-hydroxybenzo[h]quinoline-7,9-dicarbaldehyde into its derivative, unique hydroxydicarboxylic acid, by an oxidation procedure, giving 10-hydroxybenzo[h]quinoline-7,9-dicarboxylic acid. A similar procedure resulted in the formation of 9-methyl-1,10-phenanthroline-2-carboxylic acid by oxidation of commercially available neocuproine. An alternative method of obtaining 1,10-phenanthroline derivatives possessing carboxylic acid group can be based on the hydrolysis of ester or nitrile groups; however, this synthesis leads to unexpected products. Moreover, we apply Perkin condensation to synthesize a vinyl (or styryl) analog of 1,10-phenanthroline derivatives with phenol function. This reaction also demonstrates a new, simple, and efficient strategy for converting methyl derivatives of 1,10-phenanthroline. We anticipate that the new way of converting methyl will find wide application in chemical synthesis.

Structural and relational factors for successful cross-sector collaboration in home visiting: a multiple case study

BackgroundAligning delivery and financing systems across sectors to create broader systems of care can improve the health and well-being of families experiencing adversities. We aimed to identify structural and relational factors for best practices to achieve successful cross-sector collaboration among home visiting programs in the United States.Materials and methodsWe used a multiple case study approach to identify best practices for successful cross-sector collaboration between home visitors and other community service providers. We selected five diverse exemplary cases with cross-sector collaboration with variation in implementing agency type and geographic location. Cases were selected using a positive deviance approach based on strong coordination and integration with different community service provider types identified from previous survey data. We conducted in-depth qualitative interviews with home visiting staff, community providers, and clients with a total of 76 interviews conducted from 2021 to 2022. We wrote memos to synthesize themes within each case through data triangulation using interview data, documents, and site visit observations. We compared themes across the five cases to create a cross-case synthesis of best practices for successful cross-sector collaboration.ResultsAcross the five cases, relational factors including leadership from all levels, champions across sectors, and shared goals between community providers were key factors for successful collaboration. Interpersonal relationships, coupled with the desire and capacity to engage, facilitated effective coordination to address families’ needs. At the structural level, shared data systems, written agreements, and co-location enabled care coordination activities. Community Advisory Boards provided a venue for developing partnerships, relationship-building, resource-sharing, and increasing awareness of home visiting.ConclusionsWe identified key elements of successful cross-sector collaboration across five case studies where home visitors coordinate care frequently and/or are structurally integrated with a range of providers. These learnings will inform future interventions to improve home visiting collaboration with other community providers to create a system of care to enhance family well-being.

Ynamide Coupling Reagents: Origin and Advances.

Since the pioneering work of Curtius and Fischer, chemical peptide synthesis has witnessed a century's development and evolved into a routine technology. However, it is far from perfect. In particular, it is challenged by sustainable development because the state-of-the-art of peptide synthesis heavily relies on legacy reagents and technologies developed before the establishment of green chemistry. Over the past three decades, a broad range of efforts have been made for greening peptide synthesis, among which peptide synthesis using unprotected amino acid represents an ideal and promising strategy because it does not require protection and deprotection steps. Unfortunately, C → N peptide synthesis employing unprotected amino acids has been plagued by undesired polymerization, while N → C inverse peptide synthesis with unprotected amino acids is retarded by severe racemization/epimerization owing to the iterative activation and aminolysis of high racemization/epimerization susceptible peptidyl acids. Consequently, there is an urgent need to develop innovative coupling reagents and strategies with novel mechanisms that can address the long-standing notorious racemization/epimerization issue of peptide synthesis.This Account will describe our efforts in discovery of ynamide coupling reagents and their application in greening peptide synthesis. Over an eight-year journey, ynamide coupling reagents have evolved into a class of general coupling reagents for both amide and ester bond formation. In particular, the superiority of ynamide coupling reagents in suppressing racemization/epimerization enabled them to be effective for peptide fragment condensation, and head-to-tail cyclization, as well as precise incorporation of thioamide substitutions into peptide backbones. The first practical inverse peptide synthesis using unprotected amino acids was successfully accomplished by harnessing such features and taking advantage of a transient protection strategy. Ynamide coupling reagent-mediated ester bond formation enabled efficient intermolecular esterification and macrolactonization with preservation of α-chirality and the configuration of the conjugated α,β-C-C double bond. To make ynamide coupling reagents readily available with reasonable cost and convenience, we have developed a scalable one-step synthetic method from cheap starting materials. Furthermore, a water-removable ynamide coupling reagent was developed, offering a column-free purification of the target coupling product. In addition, the recycle of ynamide coupling reagent was accomplished, thereby paving the way for their sustainable industrial application.As such, this Account presents the whole story of the origin, mechanistic insights, preparation, synthetic applications, and recycle of ynamide coupling reagents with a perspective that highlights their future impact on peptide synthesis.

Assembly of Homochiral Aluminum Oxo Clusters for Circularly Polarized Luminescence.

Chiral aluminum oxo clusters (cAlOCs) are distinguished from other classes of materials on account of their abundance in the earth's crust and their potential for sustainable development. However, the practical synthesis of cAlOCs is rarely known. Herein, we adopt a synergistic coordination strategy by using chiral amino acid ligands as bridges and auxiliary pyridine-2,6-dicarboxylic acid as chelating ligands and successfully isolate an extensive family of cAlOCs. They integrate molecular chirality, absolute helicity, and intrinsic hydrogen-bonded chiral topology. Moreover, they have the structural characteristics of one-dimensional channels and replaceable counteranions, which make them well combined with fluorescent dyes for circularly polarized luminescence (CPL). The absolute luminescence dissymmetry factor (glum) of up to the 10-3 order is comparable to several noble metals, revealing the enormous potential of cAlOCs in low-cost chiral materials. We hope this work will inspire new discoveries in the field of chirality and provide new opportunities for constructing low-cost chiral materials.

Visible-Light-Promoted Selenylation/Cyclization of o-Alkynyl Benzylazides/o-Propargyl Arylazides: Synthesis of Seleno-Substituted Isoquinolines and Quinolines.

A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.

Nickel‐Catalyzed Synthesis of Thioesters from Amides and Disulfides

AbstractA novel nickel‐catalyzed practical and simple synthesis of thioesters from amides and disulfides has been developed. Diverse substituted aromatic amides are capable of coupling with diaryl or dialkyl disulfides via C−N/S−S bonds cleavage to produce the desirable thioesters in moderate to good yields. This procedure features cheap metals, novel and easily preparative substrates, providing a simple and practical access to a variety of thioesters without toxic thiols or CO gas.

Examining the Synthesis of Islamic Commercial Principles and Local Customary Practices: A Case Study of Nyambut Sawah Traditions in Tejamari, Banten

Examining the Synthesis of Islamic Commercial Principles and Local Customary Practices: A Case Study of Nyambut Sawah Traditions in Tejamari, Banten