Vol. 24 No. 1 (2026)
Published:
2026-05-01
Full Issue
Original Researches
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A Universal Method for the Determination of Amlodipine in Industrial and Extemporaneous Pharmaceutical Preparations
A universal UV spectrophotometric method for determining amlodipine besylate in industrially manufactured and extemporaneously prepared medicinal products in the form of tablets, powders, and oral solutions has been developed and validated. The methodological concept is based on the use of a single analytical model applicable to various dosage forms and dissolution media without modifying the analytical conditions. Spectral studies confirmed the presence of two absorption maxima at (238 ± 2) nm and (365 ± 2) nm, which corresponded to different chromophoric systems of the molecule and could be used to identify the compound; the wavelength of 365 nm was selected as the analytical wavelength, providing improved selectivity for the quantitative determination of the active pharmaceutical ingredient. The method was validated in accordance with pharmacopoeial requirements and ICH guidelines. The procedure is characterized by precision, accuracy, specificity, and linearity in the range of 0.04–0.06 μg mL-1 (80–120% of the nominal concentration) (r > 0.9981) in all solvents proposed. The limits of detection (LOD) and quantification (LOQ) calculated were 0.59% and 0.92% for medicinal products in tablet and powder dosage forms, and 0.84% and 1.09% for the oral solution, respectively. The uncertainty of the method, including contributions from the sample preparation and the final analytical operation, was within acceptable limits for spectrophotometric assay procedures. The method proved to be applicable to industrial tablets, as well as extemporaneous powders and oral solutions, without interference from excipients in different dissolution media. Due to the minimal solvent consumption and the absence of requirements for chromatographic equipment, the approach proposed is an environmentally friendly, affordable and acceptable alternative from the point of view of regulatory requirements for the routine quality control of amlodipine medicinal products, particularly in small-scale production.
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The improved synthesis of ROCKYPhos and its application for the asymmetric hydrogenation of dihydroisoquinoline derivatives
An optimized approach to the multigram synthesis of [(1R,2R,3S)-(+)-1,2-dimethyl-2,3-bis(diphenylphosphinomethyl)cyclopentyl]methanol (ROCKYPhos, CatASium I®), a camphor-derived chiral diphosphine ligand, has been developed. The key improvement in the synthetic scheme involved the oxidative cleavage of 3,9-dibromocamphor with V2O5 – HNO3 or NH4VO3 – Cu(NO3)2 – HNO3 system, which gave the corresponding dicarboxylic acid in the yield of 28% and significantly reduced the reaction sequence. The NMR study of a diselenide derivative of ROCKYPhos showed that one of the PPh2 groups had strong donor properties comparable to those of trialkylphosphines. The asymmetric hydrogenation of N-acetyl-1,2-dihydroisoquinoline-4-carboxylates in the presence of ROCKYPhos provided target tetrahydroisoquinolines with up to 52% ee – an outstanding result for this substrate class.
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The synthesis of (±)-(1R,6R,7R)-2-azabicyclo[4.2.0]octan-7-ol
An approach to the synthesis of (±)-(1R,6R,7R)-2-azabicyclo[4.2.0]octan-7-ol, a promising amino alcohol building block for drug discovery, has been described. The method is based on [2+2] the cycloaddition of tert-butyl vinyl ether and a ketene generated in situ from a glutaric acid derivative, as well as the intramolecular lactam formation as the key steps. Although the [2+2] cycloaddition step and further transformations proceeded without any notable stereoselectivity, the title compound was synthesized in an amount greater than 30 g with a high diastereomeric purity. This was provided by the physical properties of the intermediate (±)-(1R,6R,7R)-7-(tert-butoxy)-2-azabicyclo[4.2.0]octan-3-one that was easily separated by crystallization.
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The Synthetic Access to Fused 6,7,8,9-Tetrahydro- 5H-pyridoazepines: Evaluation of Ring-Closure Strategies
The synthetic accessibility of fused pyridoazepane frameworks was investigated through a series of strategies designed to construct differently fused azepane systems. Several precursor designs enabling alternative ring-closure topologies were explored. A “lactam” pathway proved synthetically inaccessible under various conditions due to chemoselectivity issues and competing intermolecular processes. In contrast, an efficient route to the 6,7,8,9-tetrahydro-5H-pyrido[3,2-c]azepine framework was achieved via an intramolecular cyclization strategy, in which the amine functionality was introduced prior to ring assembly. The developed route proceeds under practical laboratory conditions using inexpensive reagents and was demonstrated on a gram scale. These findings provide insight into the structural factors governing ring-closure efficiency in pyridoazepine systems and establish a practical entry to a previously underexplored fused heterocyclic scaffold.
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An Efficient Method for the Synthesis of Benzofused Five-Membered Cyclic Sulfamates
An efficient and scalable method for the synthesis of 1,2,3-benzoxathiazole 2,2-dioxides and related five-membered cyclic sulfamates employing gaseous sulfuryl fluoride (SO2F2) in the presence of Et3N is described. The one-pot cyclization of 2-aminophenol derivatives proceeds at rt and tolerates a variety of substituents on the aromatic ring, including electron-withdrawing groups, as well as N-substituted substrates. The method provides the target heterocycles in improved yields compared to classical SO2Cl2-based protocols and is readily scalable to 50 g without loss of efficiency. A virtual library of 49 cyclic sulfamate derivatives was generated and evaluated using the LLAMA approach. The library members exhibit favorable lead-like physicochemical profiles, with 100% compliance with the Lipinski, Veber, Muegge, and GSK 4/400 filters, supporting the utility of the proposed chemotypes for medicinal chemistry applications.
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Multigram-Scale Access to 2-Oxaadamantan-1-amine and 2-Oxaadamantan-1-ol via Optimized Synthesis of Bicyclo[3.3.1]nonane-3,7-dione
Practical, tens-of-grams-scale access to 2-oxaadamantan-1-amine and 2-oxaadamantan-1-ol – two overlooked heteroadamantane building blocks of interest for medicinal chemistry – has been achieved through optimization and scale-up of existing literature protocols. The key precursor, bicyclo[3.3.1]nonane-3,7-dione, and both target compounds are obtained in good overall yields using straightforward procedures and standard reagents. Notably, 2-oxaadamantan-1-amine is an exceptionally stable N,O-acetal, in stark contrast to the high hydrolytic lability usually seen in this compound class.
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Preparation of Partially Saturated Furo[3,2-c]- and Furo[2,3-c]annulated N-Heterocycles
Practical, multi-gram routes to three med-chem-relevant partially saturated furo[3,2-c]- and furo[2,3-c]annulated N-heterocycles are described. The key β‑(furyl)ethylamine intermediates were accessed via DPPA-mediated Curtius rearrangement, replacing the traditional Henry/LAH sequence and eliminating stoichiometric metal-hydride reductions. The tetrahydrofuropyridine cores were then assembled through Pictet-Spengler cyclization, while a previously unavailable dihydrofuropyridinone was obtained via Dieckmann/Feist-Benary annulation. All sequences proceed in ≤6 steps from commercial starting materials.
