Practical Synthesis Research Articles

Plant Taxonomy - Its Past Role and Future Lines of Action in India

The history of floristic and taxonomic research in India is briefly reviewed and the decline and revival of floristic studies in India is traced.Modern concepts in plant taxonomy are towards the synthesis of orthodox taxonomic practices and modern methodologies. There need not be any clash between the so called alpha and omega taxonomists. All data that can be readily scanned for the species is useful for the taxonomist. The only aspect that has to be considered is the utillty of classification for a specified purpose. A field, or forest botanist needs diagnostic keys based on superficial morphological characters for identification of plants in the field. Characters based on anatomy, embryology chromosome structure and number, palynology, plant alkaloids and protein serum analysis are useful tools for finding out the systematic position of plants of doubtful affinity; however,. these characters cannot be readily used in the field for identification of plants. The herbarium identification of plants is the simple method of retrieval of plant identity through standard specimens properly authenticated by an expert. It does not give legality for the concept of fixity of species as wrongly alluded to by some non-taxonomists, since Nomenclatural Type is a constituent element of a taxon and it is not necessarily the most representative element.Some of the lines where taxonomists could play a major role are the inventory listing of plants for the conservation of species, monitoring rate of decline and spread of species, establishment of botanical record centres, environmental education and collaboration with universities for reorientation of teaching methods.The necessity for floristic training is stressed and a syllabus drawn up.

Practical Synthesis of Chiral α-Aminophosphonates with Weak Bonding Organocatalysis at ppm Loading.

α-Aminophosphonic acids as an important class of bioisosteres of α-amino acids demonstrate various biologically important activities. We report here the development of a highly enantioselective isomerization of α-iminophosphonates enabled by an extraordinarily efficient organocatalyst. This organocatalyst afforded a total turnover number (TON) of 20,000-1,000,000 for a wide range of α-alkyl iminophosphonates. Even at a parts-per-million (ppm) loading, this catalyst achieved a complete reaction in greater than 93% enantiomeric excess (ee). Computational studies revealed that this small-molecule catalyst achieved enzyme-like efficiency via a network of weak bonding interactions that effectively preorganized the substrate and catalyst toward a transition-state-like complex. Considering the substrate tolerance, catalytic efficiency, and mechanism, this organocatalyst could be regarded as a small-molecule isomerase.

Photocatalytic Annulation of Enaminones with Thioureas for the Synthesis of 2-Aminothiazoles via Tandem C–S and C–N Bond Formation

AbstractVisible-light photocatalytic reactions between enaminones and thioureas leading to thiazole products have been achieved. The annulation process consists of tandem C–S and C–N bond formation by running reactions under air atmosphere at ambient temperature. Broad substrate tolerance of the sustainable protocol has been verified by the practical synthesis of divergent thiazoles with both monocyclic and fused cyclic structures.

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis.

In keeping with our investigation, a simple and practical synthesis of novel heterocyclic compounds with a sulfamoyl moiety that can be employed as insecticidal agents was reported. The compound 2-hydrazinyl-N-(4-sulfamoylphenyl)-2-thioxoacetamide 1 was coupled smoothly with triethylorthoformate or a variety of halo compounds, namely phenacyl chloride, chloroacetyl chloride, chloroacetaldehyde, chloroacetone, 1,3-dichloropropane, 1,2-dichloroethane, ethyl chloroformate, 2,3-dichloro-1,4-naphthoquinone, and chloroanil respectively, which afforded the 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives. The new products structure was determined using elemental and spectral analysis. Under laboratory conditions, the biological and toxicological effects of the synthetic compounds were also evaluated as insecticides against Spodoptera littoralis (Boisd.). Compounds 3 and 5 had LC50 values of 6.42 and 6.90 mg/L, respectively. The investigated compounds (from 2 to 11) had been undergoing molecular docking investigation for prediction of the optimal arrangement and strength of binding between the ligand (herein, the investigated compounds (from 2 to 11)) and a receptor (herein, the 2CH5) molecule. The binding affinity within docking score (S, kcal/mol) ranged between -8.23 (for compound 5), -8.12 (for compound 3) and -8.03 (for compound 9) to -6.01 (for compound 8). These compounds were shown to have a variety of binding interactions within the 2CH5 active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have 2CH5-inhibitory capabilities and hence may be used for 2CH5-targeting development. Furthermore, the three top-ranked compounds (5, 3, and 9) and the standard buprofezin were subjected to density functional theory (DFT) analysis. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy difference (ΔE) of compounds 5, 3, and 9 was found to be comparable to that of buprofezin. These findings highlighted the potential and relevance of charge transfer at the molecular level.

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions.

Diaryliodonium(III) salts are versatile reagents that exhibit a range of reactions, both in the presence and absence of metal catalysts. In this study, we developed efficient synthetic methods for the preparation of aryl(TMP)iodonium(III) carboxylates, by reaction of (diacetoxyiodo)arenes or iodosoarenes with 1,3,5-trimethoxybenzene in the presence of a diverse range of organocarboxylic acids. These reactions were conducted under mild conditions using the trimethoxyphenyl (TMP) group as an auxiliary, without the need for additives, excess reagents, or counterion exchange in further steps. These protocols are compatible with a wide range of substituents on (hetero)aryl iodine(III) compounds, including electron-rich, electron-poor, sterically congested, and acid-labile groups, as well as a broad range of aliphatic and aromatic carboxylic acids for the synthesis of diverse aryl(TMP)iodonium(III) carboxylates in high yields. This method allows for the hybridization of complex bioactive and fluorescent-labeled carboxylic acids with diaryliodonium(III) salts.

Engineering the substrate acceptance of l-amine dehydrogenase enables the collective biocatalytic synthesis of N-heterocyclic primary amines

Chiral N-heterocyclic primary amines are highly attractive synthons in the pharmaceutical industry. Amine dehydrogenases (AmDHs)-catalyzed direct asymmetric reductive amination of the readily available N-heterocyclic ketones represents a promising approach for synthesizing N-heterocyclic primary amines. However, the limited substrate acceptance of AmDHs restricts their application in biocatalytic synthesis. Here, we engineered the substrate acceptance of L-EsAmDH from Exiguobacterium sibiricum to access a panel of structurally diverse N-heterocyclic ketones. Through reverse substrate design and combining with substrate walking strategy, two active mutants with extended substrate specificity toward N-Boc-4-acetylpiperidine were identified, and two additional rounds of iterative site mutagenesis further increased the activity by 116.3-fold. The optimal mutant M4-2 (L49G/V303A/L307A/T143A) exhibited significantly expanded N-Boc, N-Bn, and N-Cbz-substituted heterocyclic ketones scope, and its practical biocatalytic synthesis performance was verified in the gram-scale synthesis of (R)-4-aminoethyl-1-Boc-piperidine, achieving 95 % conversion, >99 % ee, and an overall isolated yield of 86 % (9.8 g). Our study lays the foundation for the collective biocatalytic synthesis of structurally diverse N-heterocyclic primary amines and gives referable guidance for engineering AmDH family members into versatile biocatalysts.

Efficient photocatalytic hydrogen production of Ni-Co layered double hydroxides (Ni-Co LDHs) anchored with reduced graphene oxide (rGO) hybrid composite

Using a suitable co-catalyst to boost photocatalytic H2 evolution from water splitting is crucial. Herein, we designed pristine NiCo-LDH and reduced graphene-oxide supported nickel-cobalt layered double hydroxide nanosheets (NiCo-LDH/rGO) as photocatalyst for the first time to evaluate the hydrogen production performance. Adding graphene has the potential to significantly increase electrical conductivity, and the supported NiCo-LDH has the potential to significantly reduce the likelihood of graphene self-aggregation. The effectiveness of its photocatalytic hydrogen generation was analyzed using a set of characterizations. The H2 evolution rates for pure rGO were 345.2 μmolh-1g-1, whereas those for Ni-Co LDH/rGO were 578.2 μmolh-1g-1. Average hydrogen generation per hour for the Ni-Co LDH/rGO composite material was 2032.1 μmolh-1g-1, which was 5.8 and 3.5 times that of rGO and Ni-Co LDH/rGO, respectively, NiCo-LDH@rGO's synergistic impact on the NiCo-LDH boosts the H2 generation pathway by increasing the catalyst's stability as well as performance by exposing active sites and speeding up electron transport. The produced nanocomposite shows excellent spatial charge separation and quicker electron transport across the conductive network of rGO, as shown by the photocurrent response test and photoluminescence (PL) spectra. The results of this study provide a fresh perspective on the practical use and synthesis of the inexpensive and effective NiCo-LDH/rGO, demonstrating the standard deviation of logical planning and preparation of high-performance photocatalysts.

Dual-template synthesis of SFO-type aluminophosphate with enhanced water-sorption-driven cooling performance

Water-based adsorption chillers (ADC) driven by low-grade thermal energy are environment-friendly alternatives to the traditional compression ones to realize the net zero carbon target. Aluminophosphates molecular sieve (AlPOs) is an excellent material for water-based adsorption applications. However, AlPOs suffers from relatively high cost attributed to the extensive use of expensive structure direct agents (SDAs). This study employed a dual-template method, using cheap organic amine as a dual-template, to synthesize low-cost and excellent adsorbent AlPOs with SFO topology (AlPO-SFO). AlPO-SFO synthesized with dual templates shows high crystallinity, large micropore volume, excellent water uptake, and low regeneration temperature. AlPO-SFO guided by 4-dimethylaminopyridine (4-DMAPy) and diethanolamine (DEOA) molar composition of 0.4 and 0.1 exhibits large microporous volume (0.30 ml g−1), high water uptake (0.26 g g−1 at P/P0 = 0.25) and low regeneration temperature (65 °C). Importantly, this AlPO-SFO exhibits a high coefficient of performance (COP) of 0.89 for cooling at a low driven temperature of 64 °C. The additive amine providing alkaline medium ensures the practical synthesis of AlPO-SFO when expensive 4-DMAPy decreases, endowing the 42 % reduction of the raw material cost. The results provide a cheaper synthesis route of AlPO-SFO, which is conducive to its large-scale production as a distinguished adsorbent for adsorption chillers.

Directed Evolution and Immobilization of Lactobacillus brevis Alcohol Dehydrogenase for Chemo-Enzymatic Synthesis of Rivastigmine.

Rivastigmine is one of the several pharmaceuticals widely prescribed for the treatment of Alzheimer's disease. However, its practical synthesis still faces many issues, such as the involvement of toxic metals and harsh reaction conditions. Herein, we report a chemo-enzymatic synthesis of Rivastigmine. The key chiral intermediate was synthesized by an engineered alcohol dehydrogenase from Lactobacillus brevis (LbADH). A semi-rational approach was employed to improve its catalytic activity and thermal stability. Several LbADH variants were obtained with a remarkable increase in activity and melting temperature. Exploration of the substrate scope of these variants demonstrated improved activities toward various ketones, especially acetophenone analogs. To further recycle and reuse the biocatalyst, one LbADH variant and glucose dehydrogenase were co-immobilized on nanoparticles. By integrating enzymatic and chemical steps, Rivastigmine was successfully synthesized with an overall yield of 66 %. This study offers an efficient chemo-enzymatic route for Rivastigmine and provides several efficient LbADH variants with a broad range of potential applications.

Enhancing Teacher Professional Development: Strategies, Challenges, and Impacts on Instructional Practice and Student Learning Outcomes: A Review of Research Literature

Abstract: Teacher professional development (PD) is widely acknowledged as a critical component in enhancing educational outcomes and improving student achievement. This study provides a comprehensive review of the importance of teacher professional development, focusing on its impact on teacher effectiveness, instructional quality, and student learning outcomes. Drawing on a synthesis of empirical research, theoretical frameworks, and best practices, this paper highlights the multifaceted benefits of continuous teacher PD, examines key factors influencing its effectiveness, and identifies promising approaches for supporting teachers' ongoing growth and development. The findings underscore the significance of investing in high-quality PD initiatives to cultivate a skilled and motivated teaching workforce capable of meeting the diverse needs of 21st-century learners.

The Evolution of Tourism in Afghanistan: A Review of the Last 50 Years

The aim of this study is to provide a comprehensive review of the evolution of tourism in Afghanistan over the past 50 years, examining the factors, challenges, and opportunities that have shaped the industry's development and impact on the country's cultural, social, and economic landscapes. This review paper employed a systematic approach, including comprehensive searches using electronic databases and search engines, screening of articles based on inclusion criteria, full-text review, systematic analysis of included articles, and synthesis of key findings, methodologies, reports, news, and best practices to provide a comprehensive overview of the Evolution of Tourism in Afghanistan: A Review of the Last 50 Years. The review reveals the profound impact of the political and security situation, the influence of factors on tourist arrivals such as heritage sites and geopolitical factors, the evolution of marketing strategies and promotion efforts, and the challenges and opportunities faced by Afghanistan's tourism industry, including political instability, security concerns, inadequate infrastructure, limited financing, and negative perceptions, with the potential for sustainable development through strengthened security measures, improved infrastructure, enhanced marketing efforts, and international partnerships. In conclusion, Afghanistan has the potential to develop a thriving and sustainable tourism sector by addressing challenges, capitalizing on unique attractions, and fostering collaboration among stakeholders, leading to economic growth, cultural preservation, and employment opportunities. Strengthen security, preserve heritage, enhance marketing, collaborate with agencies, improve infrastructure, foster partnerships, and involve local communities for Afghan tourism development

Recent Synthesis of Nucleoside Phosphonate Analogs Using Olefin Cross-metathesis.

Nucleotide analogs known as acyclic and cyclic nucleoside phosphonates (ANPs and CNPs, respectively) have a variety of biological properties, including antibacterial, antiviral, antiparasitic, antineoplastic, and immunomodulatory. A strong reaction that has emerged in the last several decades has fundamentally changed our knowledge of the chemistry of nucleoside phosphonates. In particular, Olefin cross-metathesis (CM) has been a potent and practical synthesis route to produce functionalized olefins from essential alkene precursors. This review describes recent synthesis examples of ANPs and CNPs analogs using the Ru-catalyzed olefin cross-metathesis reactions. Olefin cross-metathesis reactions are performed in the olefinic parts of nucleoside and phosphonate produced by Grubbs, Hoveyda-Grubbs, and Nolan. This review presents a synthetic overview of a few chosen nucleosides with biological significance. Their biological activity results are briefly discussed.

Enantioselective Synthesis of Axially Chiral Sulfone-Containing Styrenes Based on Ion-Exchange Strategy.

A novel ion exchange strategy has been developed to enable the asymmetric construction of axially chiral sulfone-containing styrenes. This approach provides a practical synthesis pathway for various axially chiral sulfone-containing styrenes with good yields, exceptional enantioselectivities, and nearly complete E/Z selectivities. Additionally, the reaction mechanism is elucidated in detail through density functional theory (DFT) calculations.

Electron Donor-Acceptor Complex Driven Photocatalyst-Free Trifluoromethylation of Heterocycles.

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized through extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, and indolones. Notably, this approach enables the practical synthesis of trifluoromethylated quinoxalinones on a gram scale. Mechanistic investigations that incorporate radical trapping and ultraviolet/visible spectroscopy, confirmed the formation of the an EDA complex and elucidated the reaction pathways. This study highlights the crucial role of EDA photoactivation in trifluoromethylation, significantly expanding the application scope of EDA complexes in chemical synthesis.

Understanding Osteochondritis Dissecans: A Narrative Review of the Disease Commonly Affecting Children and Adolescents.

Osteochondritis dissecans (OCD) is a joint disorder predominantly affecting the knee, elbow, and ankle of children and adolescents. This comprehensive review delves into the epidemiology, etiology, clinical manifestations, diagnostic approaches, and treatment of OCD. The most common cause of OCD is repetitive microtrauma, typically associated with sports activities, alongside other significant factors such as genetic predisposition, ischemia, and obesity. In early stages or when lesions are small, OCD often presents as non-specific, vaguely localized pain during physical activity. As the condition progresses, patients may experience an escalation in symptoms, including increased stiffness and occasional swelling, either during or following activity. These symptom patterns are crucial for early recognition and timely intervention. Diagnosis in most cases is based on radiographic imaging and magnetic resonance imaging. Nonsurgical treatment of OCD in young patients with open growth plates and mild symptoms involves activity restriction, immobilization methods, and muscle strengthening exercises, with a return to sports only after symptoms are fully resolved and at least six months have passed. Surgical treatment of OCD includes subchondral drilling in mild cases. Unstable lesions involve methods like restoring the joint surface, stabilizing fractures, and enhancing blood flow, using techniques such as screws, anchors, and pins, along with the removal of fibrous tissue and creation of vascular channels. The specifics of OCD treatment largely depend on the affected site. This synthesis of current research and clinical practices provides a nuanced understanding of OCD, guiding future research directions and enhancing therapeutic strategies.

Practical Three-Component Regioselective Synthesis of Drug-Like 3-Aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines as Potential Non-Covalent Multi-Targeting Inhibitors To Combat Neurodegenerative Diseases.

Neurodegenerative diseases (NDs) are one of the prominent health challenges facing contemporary society, and many efforts have been made to overcome and (or) control it. In this research paper, we described a practical one-pot two-step three-component reaction between 3,4-dihydronaphthalen-1(2H)-one (1), aryl(or heteroaryl)glyoxal monohydrates (2a-h), and hydrazine monohydrate (NH2NH2•H2O) for the regioselective preparation of some 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnoline derivatives (3a-h). After synthesis and characterization of the mentioned cinnolines (3a-h), the in silico multi-targeting inhibitory properties of these heterocyclic scaffolds have been investigated upon various Homo sapiens-type enzymes, including hMAO-A, hMAO-B, hAChE, hBChE, hBACE-1, hBACE-2, hNQO-1, hNQO-2, hnNOS, hiNOS, hPARP-1, hPARP-2, hLRRK-2(G2019S), hGSK-3β, hp38α MAPK, hJNK-3, hOGA, hNMDA receptor, hnSMase-2, hIDO-1, hCOMT, hLIMK-1, hLIMK-2, hRIPK-1, hUCH-L1, hPARK-7, and hDHODH, which have confirmed their functions and roles in the neurodegenerative diseases (NDs), based on molecular docking studies, and the obtained results were compared with a wide range of approved drugs and well-known (with IC50, EC50, etc.) compounds. In addition, in silico ADMET prediction analysis was performed to examine the prospective drug properties of the synthesized heterocyclic compounds (3a-h). The obtained results from the molecular docking studies and ADMET-related data demonstrated that these series of 3-aryl(or heteroaryl)-5,6-dihydrobenzo[h]cinnolines (3a-h), especially hit ones, can really be turned into the potent core of new drugs for the treatment of neurodegenerative diseases (NDs), and/or due to the having some reactionable locations, they are able to have further organic reactions (such as cross-coupling reactions), and expansion of these compounds (for example, with using other types of aryl(or heteroaryl)glyoxal monohydrates) makes a new avenue for designing novel and efficient drugs for this purpose.

A practical synthesis of nitrone-derived C5a-functionalized isofagomines as protein stabilizers to treat Gaucher disease.

Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (-)-diethyl D-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising β-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 μM in recombinant human GCase activity in Gaucher cell lines.

Accessing 1,8-Naphthyridone-3-carboxylic Acid Derivatives and Application to the Synthesis of Amfonelic Acid.

1,8-Naphthyridone-3-carboxyl is the core structure of several on-market antibacterial drugs. It has prompted significant interest from the synthetic community. Here, we report a practical synthesis of diversely functionalized 1,8-naphthyridone-3-carboxylic acid derivatives starting from readily available and inexpensive nicotinic acid derivatives. All key steps have been optimized. Furthermore, the usefulness of this protocol has been exemplified by the first synthesis of amfonelic acid.

Unlocking the Power of Acyl Fluorides: A Comprehensive Guide to Synthesis and Properties

AbstractAcyl fluorides have emerged as versatile reagents in various synthetic endeavors, offering a range of advantages over their counterparts, acyl chlorides. This study delves into the properties and reactivity of acyl fluorides, particularly their reaction with amines and alcohols, to elucidate their distinct characteristics. We also introduce a facile and practical synthesis of acyl fluorides from a stable solution of CF3O− salt. Additionally, we establish an efficient one‐pot process for the direct preparation of amides or esters from corresponding acids and amines or alcohols, showcasing the remarkable efficiency of acyl fluorides in these transformations.

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.