Practical Synthesis Research Articles

Integrated Synthesis of Calcitriol and 26,27-Hexadeutero Calcitriol

Calcitriol (1α,25-dihydroxyvitamin D3, 1), a classical vitamin D drug, is indicated primarily in the treatment of patients with postmenopausal osteoporosis and renal osteodystrophy. In this study, a practical synthesis of calcitriol (1), from readily available commercial vitamin D2 (5) via hub intermediate 18, has been accomplished in 9% overall yield. This semi-synthetic process embedded four prominent elements of vitamin D chemistry: (1) cheletropic sulfur dioxide (SO2) adduction for the isomerization of the characteristic triene from (5Z,7E) to (5E,7E), or for the protection of the triene for selective ozonolysis of the side chain, and cheletropic extrusion of SO2 from the adduct in ethanolic sodium bicarbonate to retrieve the triene; (2) direct, regio- and stereoselective 1α-hydroxylation of 3β-TBS-protected (5E)-calciferol intermediate 19 using selenium dioxide in the presence of N-methylmorpholine N-oxide as a re-oxidant in a hot mixture of methylene chloride and methanol; (3) nickel(0)-mediated conjugate addition of the 22-iodide 23 to electron-deficient ethyl acrylate followed by Grignard reaction with methylmagnesium bromide to construct the calcitriol side chain; and (4) triplet-sensitized photoisomerization of 26 to access the bioactive (5Z,7E)-triene in calcitriol (1). The high-performance liquid chromatography purities of batches of the synthesized calcitriol (1) were consistently more than 99.9%, with related substances listed in the USP 2023 and EP 11.0 well controlled. This robust process proved amenable to pilot scale-up and industrial production. 26,27-Hexadeutero calcitriol (4), a deuterium-labeled calcitriol derivative, is useful as the internal standard in the bioanalysis for the quantification of calcitriol in serum. 4 was efficiently synthesized in an integrated manner from hub intermediate 18 in 48% yield.

Amplifying enantioselectivity in asymmetric transformations using heterogeneous chiral single-rhodium-site catalyst with sustained catalytic activity

Rhodium-catalyzed asymmetric reactions have played a pivotal role in the synthesis of functional chiral molecules. However, the ambiguous mechanism involving several plausible catalytically active species, the potential for catalyst deactivation and the need for constant reusability remain key challenges. Heterogeneous chiral Rh catalysts are highly desirable, but their performance has been hampered by low density and stability of catalytically active sites. Herein, we have devised a versatile methodology for fabricating highly efficient and robust chiral heterogeneous single-Rh-site catalysts by direct polymerization. The successful anchoring of single Rh-ligand species, the amplification of enantioselective inductive ability and the uniform distribution of atomic Rh sites within the resulting polymer matrix are identified as crucial factors contributing to their exceptional catalytic performance via comprehensive characterization and controlled experiments. In contrast to the corresponding homogeneous analogues, these chiral single-Rhodium-site catalysts exhibit outstanding performance, yielding enhanced enantioselectivity and broad applicability, even accommodating various functional groups. Remarkably, these results are achieved with just half catalyst dosage. Furthermore, their industrial potential is demonstrated through successful utilization in continuous flow processes and robust batch recycling. In future, we aim to expand the horizons of heterogeneous chiral single-metal-site catalysis, and bring us a step closer to practical asymmetric synthesis.

RECENT PROGRESS IN THE SYNTHESIS AND PHOTOCATALYTIC DEGRADATION OF ORGANIC POLLUTANTS BY GRAPHENE-BASED TiO2 NANOCOMPOSITE: A REVIEW

Numerous sustainable water processing techniques have been widely investigated and are capable of boosting the quality of water. Among these techniques, photonanocatalysis has stood tall with great promises in the last few decades. Nonetheless, a major challenge in the environmental remediation of photocatalyst technology is to develop an ideal photocatalyst that must have excellent photocatalytic efficiency, large specific surface area, maximum harvesting of solar energy, high durability and recyclability. Due to their stability, low toxicity, low cost and superhydrophilicity TiO2 has been used by researchers as an efficient photocatalyst for the degradation of organic pollutants. Unfortunately, it suffers greatly due to its high band gap with 3.2[Formula: see text]eV, insufficient visible light response, fast photogenerated electrons and holes recombination rate and serious agglomeration. Keeping these views, the present review highlights the principal results of studies on current practical synthesis and photocatalytic activity of graphene-based TiO2 nanocomposite materials for the treatment of water. The amalgamation of graphene oxide (GO) and reduced graphene oxide (rGO) with nanoscale TiO2 particles results in synergistic properties thereby tuning and increasing the functionality of the composite. In this regard, the review also addressed the progress and insight into graphene-based TiO2 nanocomposite in photocatalytic removal of organic pollutants including basis mechanism, possible key strategies of the composite, and an overview of how to elevate efficacy. Finally, brief challenges and future perspectives in this field are also presented. Indeed, this work illustrated that graphene-based TiO2 composite nanomaterials can be a green signal in the future of photocatalysis targeting water pollution remediation.

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.

Sonochemical Synthesis of Copper Borates: Effect of Reaction Conditions on the Characteristic Properties

The effect of ultrasonic treatment on liquid-state production and the characteristic features of synthesized powder were studied in liquid-state conditions. In sonochemical synthesis, the operation parameters of mole ratio, reaction temperature, and time were optimized. The synthesis was achieved in moderate conditions such as mole ratio of copper: sodium: boron (Cu: Na: B) 1:2:1, 70°C and 2.5 minutes. The prepared samples were identified as copper borate (Cu(BO2)2) with the powder diffraction file number "00-001-0472". The reaction yields were also increased from 50% to 71.5% with the modification of the experimental procedure. The specific FT-IR peaks were observed at 1090, 985, 872, 781 and 731 cm-1 band values. In the morphological analyses, the agglomerations of multi-angular particles were seen. The results showed the affirmative effects of the possible use of the ultrasonic treatment on both the practical synthesis and the increase of characteristics.

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.

A Practical Method for Synthesizing Iptacopan.

Iptacopan, the first orally available small-molecule complement factor B inhibitor, was developed by Novartis AG of Switzerland. Iptacopan for the treatment of PNH was just approved by the FDA in December 2023. Other indications for treatment are still in phase III clinical trials. Iptacopan is a small-molecule inhibitor targeting complement factor B, showing positive therapeutic effects in the treatment of PNH, C3 glomerulonephritis, and other diseases. Although Iptacopan is already on the market, there has been no detailed synthesis process or specific parameter report on the intermediates during the synthesis of its compounds except for the original research patent. In this study, a practical synthesis route for Iptacopan was obtained through incremental improvement while a biosynthesis method for ketoreductase was used for the synthesis of the pivotal intermediate 12. Moreover, by screening the existing enzyme library of our research group on the basis of random as well as site-directed mutagenesis methods, an enzyme (M8) proven to be of high optical purity with a high yield for biocatalectic reduction was obtained. This enzyme was used to prepare the compound benzyl (2S,4S)-4-hydroxy-2-(4-(methoxycarbonyl)-phenyl)-piperidine-1-carboxylate) white powder (36.8 g HPLC purity: 98%, ee value: 99%). In the synthesis of intermediate 15, the reaction was improved from two-step to one-step, which indicated that the risk of chiral allosterism was reduced while the scale was expanded. Finally, Iptacopan was synthesized in a seven-step reaction with a total yield of 29%. Since three chiral intermediate impurities were synthesized directionally, this paper lays a solid foundation for the future of pharmaceutical manufacturing.

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.

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.

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.

On the issue of determining the actual tax liabilities in transactions with "high tech" companies

The article is devoted to the issues of improving the methodology for determining valid tax liabilities (BOTTOM) in transactions with "high tech" companies. It is noted that due to the increase in the number of "high tech" companies, the question arises not only of the control of their chain of exchange of goods/works/services, but also of determining the rules for calculating the taxes. In this regard, the aim of the article is to develop a methodology for determining the tax liabilities when identifying transactions carried out with "high tech" companies based on an analysis of existing judicial practice. The object of scientific work is a set of socio-economic relations that arise in the process of determining the BOTTOM. The subject of the study is the methodology for determining the actual tax liabilities (BOTTOM) in transactions with "high tech" companies. The research methodology is based on the use of tools and methods for the analysis and synthesis of judicial practice, tabular and graphical methods of data visualization. The scientific novelty of this study lies in the adaptation of the general conceptual methodology for determining the actual tax obligations of Tikhonova A.V. in relation to such a type of tax schemes as a transaction with high tech companies. In the end of the article, transactions with "high tech" companies were classified, the basic method of calculating the BOTTOM for each of the types of transactions considered was determined, the main risk markers of tax evasion schemes in transactions with "high tech" companies were identified, and measures of the tax authority to prove the fact of participation of a "high tech" organization in the transaction were formulated. Thus, the article has meaningful practical significance and will be useful to a wide range of specialists from both tax authorities and consulting organizations.

A practical and scalable synthesis of ultra-long chain fatty acids avoiding column purification

Fatty acids of vegetable and animal origin are an important renewable feedstock for the chemical industry. Their application has increased multifold during the last two decades. While there are many ways to synthesize fatty acids, the chemical synthesis route offers more advantages in terms of versatility and targeted synthesis. Though remarkable achievements have been made in the field of fatty acid synthesis, it is still in the preliminary stage of optimization. In this paper, we wish to report a more practical & scalable approach for the synthesis of fatty acids with carbon atoms ranging from 20 to 45.

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.