Search Results (886)

The in situ-generated thiocarbonyl S-methanides derived from cycloaliphatic thioketones undergo (3+2) cycloaddition onto the C=C bond of levoglucosenone yielding anticipated, polycyclic tetrahydrothiophene derivatives in a regio- and stereoselective manner. The cycloaddition process occurred stereoselectively via the less hindered exo-face approach; exo-diastereoisomers were formed in all studied reactions. Some of the obtained crystalline (3+2) cycloadducts were studied by the monocrystal X-ray diffraction analysis, which unambiguously confirmed the postulated structure. Stable (3+2) cycloadducts were isolated in good yields (50–80%). 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

The synthetic strategy relies on the highly diastereoselective alkylation at the C4 position of L-pyroglutamic acid derivatives, followed by a decarboxylation-allylation process that enables the incorporation of diverse substituents, including aromatic substituents, affording trans-3,5-disubstituted γ-lactams with excellent diastereiosmeric ratio (dr > 98:2). The resulting γ-lactams were efficiently transformed into a series of α,γ-disubstituted γ-amino acids through hydrogenation and acidic hydrolysis. Furthermore, cross-metathesis reactions with styrene and 1-decene enabled the introduction of structurally diverse lipophilic side chains, furnishing the corresponding γ-amino acids in good overall yields (71–77%) and high diastereoisomeric ratio from >98:2 to 92:8. In addition, N-allylation followed by ring-closing metathesis and hydrogenation provided access to a previously unexplored conformationally constrained γ-amino acid. Overall, seven α,γ-disubstituted γ-amino acids, including fluorinated and conformationally restricted derivatives, were synthesized from common intermediates with high stereocontrol. The developed methodology offers a versatile platform for the preparation of structurally diverse and underexplored γ-amino acid building blocks of potential interest in peptide synthesis, medicinal chemistry, and antimicrobial agent development. Full article

The selective detection of small, highly hydrophilic metabolites differing only in stereochemistry represents a major challenge in biosensor development. Here, we present a computational investigation to elucidate the molecular basis of the experimentally observed selectivity of a protein-based electrochemical biosensor toward myo-inositol over D-chiro-inositol. Although the two stereoisomers differ only in the orientation of a single hydroxyl group, they induce distinct dynamic effects on the protein recognition element. Molecular docking revealed comparable binding regions and similar affinity scores, indicating that selectivity does not arise from differences in binding site or docking energy. To investigate dynamic contributions, all-atom molecular dynamics simulations were performed in triplicate (3 × 100 ns) using the AMBER99SB force field and explicit TIP3P water. Trajectory analyses showed that myo-inositol forms a more persistent hydrogen bond network, resulting in reduced residue-level flexibility, more stable ligand–protein interactions, and enhanced local structural stabilization. Overall, these findings support a dynamic model of stereoselective recognition in which ligand-induced modulation of protein conformational ensembles, rather than static affinity, governs biosensor performance. This work highlights the value of molecular dynamics simulations in the rational design of biosensors targeting structurally similar analytes. 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

Topologically chiral molecular knots and links represent a unique class of stereochemical architectures in which handedness is encoded by the global crossing pattern of an entangled framework rather than by a local stereogenic element. Their configurational robustness and shape-persistent chiral environments make them promising platforms for molecular recognition, catalysis, chiroptical response, and spin-selective transport. This review summarizes recent progress in the stereoselective synthesis of topologically chiral knots and links, with emphasis on chirality transfer from point, axial and helical elements into persistent topological handedness. Major synthetic strategies are organized into helicity-driven approaches, template-free dynamic systems, coordination-driven self-assembly, and chiral self-sorting. The applications of knots in host–guest confinement, asymmetric catalysis, chiral recognition, and spin-selective transport are also discussed. Full article

Threonine aldolases (TAs) are pyridoxal-5-phosphate (PLP)-dependent enzymes that catalyze the reversible aldol condensation between aldehydes and glycine, enabling the asymmetric synthesis of chiral β-hydroxy-α-amino acids. The discovery of new TAs has greatly enriched the enzyme family and spurred investigations into noncanonical reactions beyond conventional aldol condensation, establishing access to structurally diverse amino compounds. Protein engineering has significantly improved the catalytic performance of this enzyme class, particularly addressing the inherent limitation of low C_β-stereoselectivity. Furthermore, the integration of TAs into multi-enzyme cascade systems has broadened their synthetic applicability. This review systematically presents recent progress in biocatalysis with TAs, including the various reaction types, the engineering of TAs for improved catalytic performance, the application of the enzyme in cascade reactions, and future opportunities to broaden the utility of the enzyme class in amino compound synthesis. Full article

Background/Objectives: Jatrophone is a bioactive diterpenoid with reported antitrypanosomal activity; however, its development as a lead compound is limited by pronounced cytotoxicity toward mammalian cells. This study aimed to explore the structural modification of jatrophone through triazole functionalization to modulate its antiparasitic activity and improve selectivity against Trypanosoma cruzi. Methods: A series of mono- and bis-triazole jatrophone derivatives was semi-synthesized via Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) from a stereoselectively prepared diazido intermediate. Jatrophone, its azido precursor, and the synthesized triazole derivatives were evaluated in vitro against T. cruzi epimastigotes and intracellular amastigotes. Cytotoxicity toward mammalian host cells was assessed in parallel to determine selectivity indices. Results: Jatrophone exhibited potent activity against epimastigotes but showed poor selectivity due to significant mammalian cell toxicity. Introduction of azide and triazole functionalities altered the biological profile of the parent scaffold, leading to derivatives with reduced cytotoxicity and improved selectivity in extracellular assays. Among the evaluated compounds, a mono-triazole derivative bearing a methylene-linked cycloalkyl substituent retained antiparasitic activity while displaying markedly lower toxicity toward mammalian cells. However, in the intracellular amastigote model, most derivatives demonstrated a substantial reduction in selectivity, indicating limited translation of extracellular activity to the intracellular parasite stage. Conclusions: Triazole functionalization of the jatrophone scaffold represents a viable strategy to modulate its biological properties and reduce host-cell toxicity. Nevertheless, the reduced efficacy observed in intracellular assays underscores the limitations of epimastigote-based screening and highlights the challenges in developing selective intracellular antitrypanosomal agents from the jatrophone scaffold. 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

Ziegler-Natta (Z-N) catalysts for propylene polymerization were prepared in situ using dibutyl phthalate (DNBP) or 9,9-bis(methoxymethyl)fluorene (BMMF) as internal electron donors (IDs) by treating the support precursors (Mg(OEt)₂ or MgCl₂·2.5EtOH) or MgCl₂ complex solutions with TiCl₄ respectively. In this study, eight Z-N catalysts containing two types of IDs were prepared via different preparation routes and systematically characterized with modern analytical techniques. The results indicated that, even with the same IDs, the catalysts prepared by different methods exhibited significant differences in chemical composition, particle size distribution, catalytic activity and stereoselectivity. The properties of polypropylene (PP) were largely influenced by the preparation route of the catalysts. Particularly, the catalysts obtained by the reprecipitation method showed the highest catalytic activity and the smallest MgCl₂ particle size. The distribution of stereoselective active centers in the catalysts was simultaneously affected by the preparation method and the type of IDs. In addition, the melting point (T_m) of PP could be used as an effective indicator to evaluate the relative content of the highly isotactic active centers in the catalysts. This study provides valuable insights into the rational design of Z-N catalysts for propylene polymerization, highlighting the critical role of the preparation methodology in tailoring the catalyst properties and active center distribution. 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

L-carnitine is a crucial quaternary ammonium compound widely used in the pharmaceutical, food, and feed industries. Microbial biosynthesis of L-carnitine, compared with chemical synthesis, offers milder conditions, higher stereoselectivity, and a lower environmental impact. However, highly efficient strains and mechanistic insights into the bioconversion of γ-butyrobetaine (γBB) to L-carnitine remain limited. This study focuses on strain WQ-1, a newly screened strain capable of converting γBB to L-carnitine. Based on morphological, physiological, and phylogenetic analyses of 16S rRNA and housekeeping genes, the strain was identified as Ensifer sp. WQ-1. Under the condition of 30 °C, initial pH 8.5, 10% inoculum, 6 g/L initial γBB, shake-flask fermentation reached molar conversion rate of 88%. In a 5 L bioreactor fed-batch fermentation, the L-carnitine titer achieved 13.98 g/L with a 78.7% molar conversion rate. Genomic analysis revealed a 6.97 Mb genome harboring 6568 protein-coding genes, including candidates for quaternary ammonium transport, CoA-dependent transformation, and transcriptional regulation. Comparative transcriptomics identified 58 differentially expressed genes, highlighting the significant upregulation of genes related to acyl-CoA activation, dehydrogenation, carnitine metabolism, and thioester hydrolysis in the presence of γBB. Multi-omics analyses support a putative CoA-dependent metabolic pathway for conversion of γBB to L-carnitine in Ensifer sp. WQ-1. Full article

The combination of photochemistry with stereoselective catalysis has emerged as an effective strategy to achieve stereocontrol in light-driven transformations. Chiral phosphoric acids (CPAs) have recently attracted attention in this context due to their ability to activate substrates while providing a defined chiral environment. This minireview highlights recent developments in CPA-enabled asymmetric photochemical transformations, focusing on systems in which CPAs incorporate a chromophore on the chiral backbone or form light-absorbing CPA-substrate complexes that enable photoactivation without the presence of an external photocatalyst. The main catalytic strategies, mechanistic features, and current limitations are discussed. Full article

Over the last 20 years, Deep-Eutectic Solvents (DES) have been making a significant impact in the field of chemistry, with applications in nanotechnology, biomass transformation, electrochemistry pharmaceuticals and a host of other applications that includes catalysis. Considering the importance of chiral organocatalysis for the selective synthesis of drugs, pharmaceuticals and fragrances, etc. DESs were quickly harnessed as the media for carrying out organocatalytic transformations. In this review, we discuss some of the most important examples from the literature that have made an impact in the field over the last 5 years. A more recent development has been the incorporation of DESs in structured and self-organized gel-like assemblies that are known as EutectoGels. These soft structures offer a more defined and compact environment that can influence stereoselectivity by pre-organizing the reactants in three-dimensional space, and potential control the types of transition states that can be formed. Full article

A ligand-free Ni(acac)₂/EASC Ziegler–Natta catalytic system was developed for the efficient synthesis of low molecular weight liquid polybutadiene (LPB) featuring high 1,4 content. The influences of key polymerization parameters, including Al/Ni ratio, polymerization temperature, monomer-to-catalyst ratio ([Bd]/[Ni]), and external donors, were systematically investigated to elucidate structure–reactivity relationships. Increasing the Al/Ni ratio significantly enhances catalytic activity while promoting chain transfer reactions, leading to reduced molecular weights and broader molecular weight distributions, with minimal impact on overall 1,4 selectivity. Polymerization temperature strongly affects both activity and stereoselectivity; elevated temperatures accelerate chain transfer processes and broaden dispersity, while inducing a shift from kinetically favored cis-1,4 insertion toward increased trans-1,4 incorporation. Variation of the [Bd]/[Ni] ratio provides an effective handle for molecular weight regulation, where higher ratios favor chain propagation over chain transfer, affording higher molecular weights but lower monomer conversion. Notably, the system maintains consistently high 1,4 content (>98%) across a wide range of conditions. In contrast, the introduction of external donors markedly affects catalytic behavior depending on their coordination ability. Strongly coordinating O- and S-containing donors partially deactivate the catalyst and significantly shift regioselectivity toward 1,2-vinyl incorporation (up to ~20%), while N- and P-containing donors are well tolerated and can increase molecular weight by suppressing chain transfer pathways, which also results in products with higher 1,2 content. Full article