Search Results (951)

The enantiomeric composition of products obtained from isomerization of n-humulone 1a to trans- and cis-n-isohumulones 2a and 3a, respectively, was determined by chiral HPLC analysis of the isolated trans and cis isomers. Enantiomers of humulone 1 were readily resolved on a Whelk-O1 chiral stationary phase (CSP), whereas the isomeric isohumulones 2 and 3 were separated on a carbohydrate-based IC-3 CSP. Magnesium-catalyzed isomerization of n-humulone under basic conditions gave mixtures of trans- and cis-n-isohumulones exhibiting an increasing preference for the cis isomer at lower temperatures. At either 10 °C in CH₂Cl₂/H₂O or reflux in methanol-water, the trans-(−) (4S,5S)-2a isomer was obtained in greater than 95% ee, while diastereomeric cis-3a exhibited 88% ee of the (+)-(4S,5R) enantiomer. Precision continuous flow photochemical isomerization using 395 nm LEDs provided trans-(−)-2a in greater than 95% ee in an isolated yield of 93%. However, photochemical isomerization with 365 nm LEDs gave a mixture of isomers consisting of 46% ee for the trans-(−)-2a and greater than 95% ee for the cis-(−)-(4R,5S)-3a enantiomer. The photochemically obtained (−)-3a isomer has the opposite absolute configuration compared to thermal isomerization. An oxadi-π-methane rearrangement is proposed to account for the formation of isohumulone isomers under photochemical conditions. Full article

A series of cis-5-arylmethyl-2-alkyl-3-methylimidazolidin-4-ones, prepared from arylmethyl-substituted α-amino acids, and a series of trans- and cis-2-(fluoromethyl)-2,3-dimethylimidazolidin-4-ones, derived from L-valine and L-leucine, were synthesized and fully characterized. Their catalytic activity was evaluated in the addition of 1-methylindole to cinnamaldehyde. Using the cis-5-arylmethyl-2-alkyl-3-methylimidazolidin-4-one catalysts, enantioselectivities of up to 78% ee (S) were achieved. Notably, with the L-valine-derived cis-imidazolidinone organocatalyst, the highest reversal of stereoselectivity to date (92% ee, (R) at –43 °C) was observed. Full article

Non-heme iron enzyme-catalyzed enantioselective alkene trifluoromethyl azidation represents a powerful strategy for constructing valuable chiral organofluorine compounds, yet the mechanistic origins of enantioselectivity controlled by the key residues in the enzyme’s chiral environment remain elusive. Herein, we integrate density functional theory (DFT) calculations, classical molecular dynamics (MD) simulations, and quantum mechanical/molecular mechanical (QM/MM) calculations to elucidate the mechanism and the origin of enantiocontrol in this transformation. Our computational study reveals that radical addition from the CF₃ radical to the 4-methoxystyrene substrate constitutes the enantioselectivity-determining step. The enantioselectivity arises from energetic differences driven by H···H repulsions and C-H···O and N-H···F interactions between the substrate and the binding pocket defined by key residues I335V, F188Q, and R324 near the active site, which stabilize the transition state leading to the major enantiomer. These findings provide mechanistic insights into non-heme iron enzyme-catalyzed asymmetric azido-trifluoromethylation of alkenes and establish a structural framework for rational biocatalyst design. Full article

The catalytic enantioselective formation of carbon–sulfur (C–S) bonds is a rapidly evolving field in modern organic synthesis, driven by the importance of chiral sulfur-containing motifs in pharmaceuticals, agrochemicals, and functional materials. Despite their significance, asymmetric C–S bond-forming reactions remain challenging due to the strong coordinating ability and nucleophilicity of sulfur species, catalyst deactivation, and difficulties in controlling sulfur- or carbon-centered stereogenicity. Recent advances in transition-metal catalysis, organocatalysis, and emerging electrocatalytic strategies have enabled efficient access to diverse chiral organosulfur frameworks, including sulfides, sulfoxides, sulfilimines, sulfoximines, and sulfinamides, with high levels of enantioselectivity. These methodologies have significantly expanded the synthetic toolbox for constructing C–S bonds under mild and sustainable conditions. This review provides a concise and critical overview of catalytic enantioselective C–S bond formation, emphasizing reaction design, catalytic systems, and mechanistic aspects of enantiocontrol. Key transformations such as asymmetric allylic substitution, conjugate addition, cross-coupling, photoredox-enabled processes, and emerging electrochemical approaches are discussed. Particular attention is given to strategies for the generation and control of sulfur-centered stereogenicity. Finally, current limitations and future opportunities, including dual catalysis, late-stage functionalization, and sustainable catalytic systems, are highlighted to guide further developments in asymmetric organosulfur chemistry. Full article

The spiroindoline framework is a privileged scaffold in medicinal chemistry, appearing in natural products and in synthetic bioactive compounds, such as BAY 1214784, RO8994, and RK-287107, with reported activities ranging from antimitotic effects to kinase inhibition. This review covers the methods developed between 2020 and 2025 for constructing spiroindoline frameworks, organized first by the site of spirocyclization (C2 versus C3 of the indole) and then by catalyst class: second- and third-row transition metals, first-row transition metals and main-group Lewis acids, organocatalysis, and visible-light photoredox. For each method we discuss the reaction design, the accessible substrate scope, and mechanistic insights, with particular attention to how stereochemistry is controlled. We also highlight representative downstream transformations that demonstrate the synthetic utility of the produced spiroindolines. Progress over the past five years has been substantial, particularly in enantioselective methods that create a single stereocenter and in cascade designs that build complex polycyclic frameworks in a single operation. Asymmetric construction of multiple adjacent stereocenters, gram-scale demonstrations, and genuinely sustainable conditions remain less developed; these areas are priorities for future work. Full article

Amino alcohols are a class of compounds bearing both amino and hydroxyl groups, ubiquitous in natural products and extensively utilized as key structural motifs in pharmaceuticals and functional materials. Owing to their structural diversity, inherent chirality, and high reactivity, they exhibit significant application value in the pharmaceutical field, materials industry, and organic synthesis. Compared with chemical synthesis, which suffers from limitations such as insufficient enantioselectivity, dependence on precious metal catalysts, and environmental concerns, biosynthesis offers core advantages of high stereoselectivity, mild reaction conditions, and environmental sustainability. This review systematically delineates the diverse applications of amino alcohols in the pharmaceutical field (e.g., anti-HIV, antimalarial, and antitumor drugs), materials industry (e.g., polymer modification and metal corrosion protection), and organic synthesis (e.g., chiral ligands and catalysts). Particular emphasis is placed on the biosynthetic strategies and pathways of representative amino alcohols, including ethanolamine, (2S,3R)-2-amino-1,3,4-butanetriol, (R)-3-amino-1-butanol, sphingosine, and metaraminol, as well as the metabolic engineering design principles and downstream processing technologies for amino alcohol biosynthesis. Although current biosynthetic approaches still face bottlenecks in enzyme catalytic efficiency, substrate tolerance, cofactor regeneration, product toxicity, and thermodynamic equilibrium, substantial improvements in synthetic efficiency and stereoselectivity have been achieved through protein engineering, metabolic engineering, in situ product removal, and multi-enzyme cascade optimization. This review aims to provide systematic theoretical references and technical insights for the green and efficient biomanufacturing of amino alcohols. Full article

Idelalisib (IDE) is a marketed chiral anticancer drug administered as the S-enantiomer, requiring sensitive monitoring of the R-enantiomer to ensure enantiomeric purity. However, no dedicated capillary electrophoresis (CE) method has been reported for trace-level quantification of R-IDE. In this study, a cyclodextrin-mediated CE method was developed for reliable detection of the R-enantiomer at the 0.1% level (LOD 2 µg/mL; LOQ 5 µg/mL). Systematic screening identified hydroxypropyl-β-cyclodextrin (HP-β-CD) with an intermediate degree of substitution (DS~6.8) as the optimal chiral selector, providing efficient enantioseparation (R_s up to 4.3). The method was validated according to ICH Q2(R2) guidelines, demonstrating suitable precision, accuracy, and robustness. Complementary NMR studies revealed hindered rotation of the 3-phenyl moiety and elucidated the molecular basis of enantioselectivity. Complexation with β-CD and HP-β-CD produced clear diastereomeric differentiation in both ¹H and ¹⁹F NMR spectra, while the simplified ¹⁹F NMR profiles enabled direct enantiomer discrimination. NOESY and ROESY experiments demonstrated distinct inclusion modes, with HP-β-CD accommodating both the fluorinated aromatic ring and the 3-phenyl moiety. These interactions may account for the superior enantioseparation observed with HP-β-CD of intermediate DS. Our validated CE method addresses the distomer determination while NMR insights provide mechanistic understanding of the chiral recognition. Full article

Introduction: Synthetic cathinones (SC) are an emerging class of neuroactive contaminants increasingly detected in aquatic systems due to their widespread recreational use. Their continuous release at ng–µg L⁻¹ levels is particularly concerning, as these compounds are specifically designed to alter neural function, raising the likelihood of subtle yet ecologically relevant effects in non-target organisms. Among them, 3,4-methylenedioxypyrovalerone (MDPV) is one of the most-reported SC in wastewater and surface waters. Nevertheless, its chiral nature has been largely overlooked in ecotoxicological studies, despite growing evidence that enantiomers can differ markedly in biological activity, potentially leading to underestimated environmental risks. Objective: The ecotoxicological impact of racemic MDPV ((R,S)-MDPV) and its separate enantiomers ((R)-MDPV and (S)-MDPV) were examined using zebrafish (Danio rerio) as a model, focusing on survival and embryonic development. Methodology: Zebrafish embryos, at approximately 3-hours post-fertilization (hpf), were exposed over 96 h to environmentally relevant concentrations of MDPV forms (0.18−2.8 μg L⁻¹). Each treatment and control group included 50 animals distributed across 5 replicates. Mortality was assessed at multiple developmental stages (7, 24, 48, 72, and 96 h), along with cumulative mortality. Developmental endpoints included spontaneous movements (24 h), heartbeat (48 h), and hatching rate (48 and 72 h), quantified using stereomicroscopy and video analysis. Results: MDPV showed concentration and enantioselective effects, with (S)-MDPV being the most toxic. Behavioral and cardiac responses varied across forms, while hatching depended on concentration and time without a clear enantioselective pattern. Conclusions: MDPV disrupts early zebrafish development, impairing survival and embryonic development in a concentration-dependent and enantioselective manner, with (S)-MDPV demonstrating greater toxicity. These findings emphasize the importance of considering chirality in the environmental risk assessment of psychoactive contaminants such as SC, as enantiomer-specific effects may influence organism fitness, survival, and broader ecological outcomes. Full article

The use of water as a nucleophile in catalytic asymmetric reactions remains a significant challenge, primarily due to its intrinsically low nucleophilicity and small size, which make precise control over both reactivity and stereoselectivity particularly difficult. To address this issue, we developed a CPA-catalyzed asymmetric hydrolysis system, successfully achieving the efficient and highly stereoselective transformation of 4H-oxazines with water. Under this catalytic system, the initial formation of chiral α-bromo ketones is followed by their in situ conversion through reduction and intramolecular S_N2 reactions, directly affording valuable chiral bromo alcohols and chiral oxazolone derivatives in high yields with excellent enantioselectivity. Full article

Chiral pharmaceuticals (CPs) have gained growing attention in environmental studies regarding the differential behavior of individual enantiomers in racemic mixtures. This study investigates the stereoselectivity and efficiency of montmorillonite (MMT), a natural and low-cost adsorbent, for the removal of a wide group chiral pharmaceuticals and metabolites (atenolol, propranolol, metoprolol, fluoxetine, venlafaxine, norfluoxetine, and O-desmethylvenlafaxine). The effects of adsorption conditions including initial CP concentration, contact time, adsorbent dose, solution pH, and humic acid content were evaluated. In most adsorption experiments, no significant stereoselective behavior was observed, except for the case where a low adsorbent dose was applied. Interestingly, as the solution humic acid content increased (up to 40 mg/L), the adsorption capacity was increased for most of the target CPs. Isotherm studies revealed that the Freundlich model described the experimental data well and the process was favorable. Adsorption mechanism was interpreted by material characterization before and after adsorption. High removal efficiencies (88.0 to 99.8%) and the non-enantioselective behavior of MMT indicate that it can be used effectively for the simultaneous removal of both enantiomeric forms of various chiral pharmaceuticals from aqueous matrices. Full article

We report the synthesis, characterisation and electronic modulation of three novel fused polyheterocyclic ligands—naphtho[1,2-b]furan-4,5-dione (1), furo[3′,2′:3,4]naphtho[1,2-d]imidazole (2), and benzo[a]furo[2,3-c]phenazine (3)—and their Cu(II), Zn(II) and Fe(II/III) complexes. Compound (1) was isolated at 96.5% yield using fulvic acid as a green organocatalyst. ⁵⁷Fe Mössbauer spectroscopy identified two high-spin Fe(III) environments in a 37:63 ratio (δ = 0.377 mm s⁻¹; Δ = 0.62 and 1.01 mm s⁻¹), with no evidence of magnetically ordered oxide phases. Six enantiomeric metal malate salts were synthesised at 86–93% yield for spectrophotometric titrations. The key finding is a striking Cu(II)-specific enantioselective molecular recognition: (3) binds (S)-(−)-malate Cu(II) with log K = 9.02, a factor of 2.5× higher than the (R)-(+)-malate complex (log K = 8.62), while Fe(II) and Zn(II) show no enantioselectivity. These results establish chiral counter-ion engineering combined with π-conjugated polyheterocyclic scaffolds as a powerful strategy for chiroptical sensing and asymmetric catalysis. Full article

1,2,4-Trisubstituted chiral homoallylic alcohols are valuable intermediates in natural product synthesis and complex molecular architectures; however, their catalytic asymmetric synthesis remains challenging due to the need for precise control of regioselectivity, diastereoselectivity, E/Z geometry, and enantioselectivity. Herein, we report a palladium-catalyzed enantiospecific three-component reaction of aldehydes, borylated allyl acetates, and dimethylzinc for the efficient synthesis of 1,2,4-trisubstituted anti-(Z)-homoallylic alcohols. The present method employs readily accessible chiral borylated allyl acetates and proceeds with high levels of stereochemical control, providing a practical approach to structurally complex homoallylic alcohols. Full article

Life demonstrates remarkable homochirality of its major building blocks: nucleic acids, amino acids, sugars, and phospholipids. Phospholipid bilayer vesicles (liposomes) are formed at the water/air interface from Langmuir layers and contain ribose, a constituent of primordial water. Although the primordial ribose was initially racemic, life, as we know it, is homochiral, with d-ribose and its derivatives as the predominant forms. The phospholipid membrane’s permeability to d-ribose, together with ribose’s interaction with the bilayer’s charged phosphate groups, leads to ribose phosphorylation, yielding d-ribose-5-phosphate. Once inside, the d-ribose-5-phosphate molecules cannot cross the membrane. A similar path also exists for l-ribose, but with a lower rate. Therefore, overall, this process is enantioselective, favoring the buildup of d-ribose over l-ribose. Through liposome fusion, fission, and self-replication, this eventually leads to the Darwinian evolution of these structures and to the conversion of d-ribose-5-phosphate into complex functional molecules, such as ribozymes and RNA, and eventually into DNA, all of which inherit d-ribose’s chirality. Full article

Chirality is a cornerstone of biological systems and pharmaceutical activity, driving a critical need for rapid and sensitive enantioselective analytical methods. Covalent organic frameworks (COFs) have emerged as versatile porous materials, and their chiral counterparts, chiral COFs (CCOFs), uniquely combine high surface area, pre-designable pores, and a confined chiral microenvironment, making them exceptional platforms for enantioselective fluorescence sensing. This review systematically summarizes recent advances in the construction and application of CCOFs for enantioselective fluorescence sensing. We first outline the primary synthetic strategies for CCOFs, including direct synthesis, post-synthetic modification, and chiral induction. Subsequently, based on the direction of fluorescence signal change upon analyte binding, we classify the sensing mechanisms into three categories: “turn-off” (quenching via static complexation or photoinduced electron transfer), “turn-on” (enhancement through rigidification or suppression of electron transfer), and ratiometric (self-calibrating dual-emission response). Representative examples for the detection of amino acids, amino alcohols, terpenes, and saccharides are highlighted for each mode. Special emphasis is placed on structure–property relationships, such as the synergistic roles of hydrogen bonding, π–π stacking, and framework confinement in amplifying enantioselectivity. Finally, we discuss current challenges and future perspectives, including the rational design of ratiometric sensors, integration into practical devices, and the convergence with machine learning to advance the field of smart chiral sensing. Full article

Chirality has emerged as a critical determinant in the design, efficacy, and environmental behavior of modern insecticides. While a significant proportion of agrochemicals are inherently chiral, most are still commercialized as racemic mixtures, despite well-documented differences in biological activity, toxicity, and degradation pathways between enantiomers. In this review, we provide a comprehensive and critical analysis of advances in the stereoselective synthesis and resolution of chiral insecticides, with particular emphasis on neonicotinoids, pyrethroids, and oxadiazines, including indoxacarb. A systematic survey of the literature (1985–2025), including peer-reviewed articles and patents, reveals that multiple strategies have been developed to access enantiomerically enriched compounds, including asymmetric organocatalysis, transition-metal catalysis, chiral-pool approaches, biocatalytic transformations, and chromatographic resolution techniques. Among these, recent developments in photoredox catalysis, recyclable metal complexes, and enzyme-mediated processes have significantly improved enantioselectivity and scalability, bridging the gap between academic methodologies and industrial applications. Despite these advances, challenges remain in achieving cost-effective, sustainable, and universally applicable asymmetric processes. Importantly, the relationship between stereochemistry and biological performance underscores the need for integrating synthetic chemistry with toxicological and environmental studies. Future directions point toward the incorporation of green chemistry principles, continuous-flow processes, and computational tools, including machine learning and molecular modeling, to accelerate the rational design of enantiopure agrochemicals. This review highlights both the progress achieved and the critical gaps that must be addressed to realize the potential of stereoselective insecticide development fully. Full article