Epoxide Ring-opening Reaction Research Articles

Ring opening of epoxides: a facile approach towards the synthesis of polyketides and related stereoenriched natural products: a review.

Epoxides are significant heterocycles in the structural makeup of a variety of natural products. Their ring-opening reactions have emerged as a versatile and efficient strategies for synthesizing a variety of functionalized molecules. Such reactions have been extensively applied towards the preparation of complex naturally occurring products. The focus on epoxide ring-opening reactions within the scientific community has been increased, influenced by the goal to understand the synthesis of compounds that are important for their biological and structural significance. In this article, we have provided a concise account on the applications of epoxide's ring cleavage towards the syntheses of polyketides and related naturally occurring compounds, documented since last decade (2014-2023).

Synthesis of Cyclic Diglycerols: The Utility of the BF3·OEt2-Mediated Intramolecular Epoxide Ring-Opening Reaction for the Cyclic Polyglycerol Synthesis.

We reported the synthesis of cyclic diglycerol, which was the minimum unit in polyglycerols. Epoxy alcohols of a linear diglycerol were treated with catalytic amount of boron trifluoride etherate (BF3·OEt2) in high diluted dichloromethane (CH2Cl2) to give the corresponding 1,4-dioxepane and 1,4-dioxane type cyclic diglycerols in high yield as a single structural isomer. The structures of the cyclic products were determined by 1D and 2D NMR spectral analysis. The results investigated the cyclization were dominated to Baldwin’s rule. The synthesized cyclic diglycerol can use as a standard.

Siloxane-based oligomer ligands of indium phosphide quantum dots for improving dispersion in a siloxane matrix

The ligands of indium phosphide (InP) quantum dots (QDs) were modified with siloxane-based oligomers in a two-step process to improve the dispersion of InP QDs in a siloxane-based matrix. Oleic acid ligands on InP QDs (InP-OA) were exchanged with 6-mercapto-1-hexanol. Then, the hydroxyl functional groups (–OH) of the ligands were induced to react with poly(dimethylsiloxane), diglycidyl ether terminated (PDMS-DGE) by a ring-opening reaction of epoxide. The chemical bonding between the hydroxyl groups and PDMS-DGE was confirmed by Fourier-transform infrared (FT-IR) spectroscopy. The synthesized InP QDs with PDMS-DGE ligands (InP-PDMS-DGE) were blended with acrylate-siloxane polymers to produce color conversion QD films. The photoluminescence (PL) intensity of the QD films with the InP-PDMS-DGE QDs was improved by 2.3 times compared with that of InP-OA QDs. The color conversion efficiency of the QD films was determined using a blue light-emitting diode (LED), and the QD film containing InP-PDMS-DGE QDs demonstrated a conversion efficiency of 21%, compared to a lower efficiency of 17% for a film containing InP-OA QDs. The stability of the InP-PDMS-DGE film was tested at 85°C with a relative humidity (RH) of 85%, demonstrating an improvement of 28% compared to that with an InP-OA film.

Synthetic Process Development of (R)-(+)-1,2-Epoxy-5-hexene: An Important Chiral Building Block.

Herein, we describe two practical approaches to synthesize (R)-(+)-1,2-epoxy-5-hexene from inexpensive and readily available raw materials and reagents. The first approach is a two-step sequence, involving an epoxidation with meta-chloroperoxybenzoic acid (mCPBA) and a chiral resolution with (salen)Co(II), producing (R)-(+)-1,2-epoxy-5-hexene in 24-30% overall yield. The second approach utilizes readily available (R)-epichlorohydrin as the starting material and features an epoxide ring-opening reaction with allylMgCl and the NaOH-mediated ring closure reaction. Development of this two-step process affords R-(+)-1,2-epoxy-5-hexene in overall isolated yields of 55-60% with an exceptional purity profile. Both approaches have been successfully demonstrated on 100-200 g scales.

Remediation of water containing lead(II) using (3-iminodiacetic acid) propyltriethoxysilane graphene oxide

A novel chelating adsorbent based on (3-iminodiacetic acid) propyltriethoxysilane graphene oxide (IAT-GO) has been developed, showing exceptional promise for capturing lead. IAT-GO is made by combining a high-surface-area graphene oxide with a specially designed chelating ligand, which can selectively and efficiently remove lead. The synthesis of IAT-GO involves a two-step progression. In the first step, covalent bonds form between graphene oxide and (3-aminopropyl)-triethoxysilane (AT) through hydrolysis, condensation, and epoxide ring opening reactions. In the second step, nucleophilic substitution reactions occur between the primary amines and chloroacetic acid (CAA). A comprehensive suite of characterization techniques, including XPS, UV–Vis, XRD, Raman, FTIR, TEM, and SEM, provides detailed insights into the IAT-GO adsorbent's chemical composition and physical form, elucidating its intricate structure and morphology. Optimizing the experimental conditions for using the adsorbent material to remove Pb(II) ions from contaminated water revealed a maximum adsorption capacity of 124.0 mg/g at pH 5 and 30 min. The IAT-GO displays high selectivity for Pb(II) in a mixture of six metal ions containing 100 ppm of each one. Moreover, the IAT-GO shows 100% removal of Pb(II) for concentrations lower than 50 ppm. The excellent fit of the experimental data with the Langmuir adsorption isotherm and pseudo-second-order kinetic models (R2 > 99%) indicates that Pb(II) ion uptake onto the IAT-GO surface occurs via the monolayer formation of mercury ions. IAT-GO demonstrates exceptional potential as an innovative adsorbent for lead-contaminated water. Nitric acid (0.4 M) effectively regenerates the material, while its reusability remains impressive even after five cycles (> 97% removal efficiency). Therefore, this study highlights the development of a groundbreaking material, IAT-GO, with exceptional potential for remediating lead-contaminated water. Its high efficiency, selectivity, reusability, and cost-effectiveness make it a promising candidate for real-world applications.

Superior and efficient performance of cost-effective MIP-202 catalyst over UiO-66-(CO2H)2 in epoxide ring opening reactions

This study explored the catalytic performance of two robust zirconium-based metal–organic frameworks (MOFs), MIP-202(Zr) and UiO-66-(CO2H)2 in the ring-opening of epoxides using alcohols and amines as nucleophilic reagents. The MOFs were characterized by techniques such as FT-IR, PXRD, FE-SEM, and EDX. Through systematic optimization of key parameters (catalyst amount, time, temperature, solvent), MIP-202(Zr) achieved 99% styrene oxide conversion in 25 min with methanol at room temperature using 5 mg catalyst. In contrast, UiO-66-(CO2H)2 required drastically harsher conditions of 120 min, 60 °C, and four times the catalyst loading to reach 98% conversion. A similar trend was observed for ring-opening with aniline –MIP-202(Zr) gave 93% conversion in one hour at room temperature, while UiO-66-(CO2H)2 needed two hours at 60 °C for 95% conversion. The superior performance of MIP-202(Zr) likely stems from cooperative Brønsted/Lewis acid sites and higher proton conductivity enabling more efficient epoxide activation. Remarkably, MIP-202(Zr) maintained consistent activity over five recycles in the ring-opening of styrene oxide by methanol and over three recycles in the ring-opening of styrene oxide by aniline. Testing various epoxide substrates and nucleophiles revealed trends in reactivity governed by electronic and steric effects. The results provide useful insights into tuning Zr-MOF-based catalysts and highlight the promise of the cost-effective and sustainable MIP-202(Zr) for diverse epoxide ring-opening reactions on an industrial scale.

Origin of Chemoselectivity of Halohydrin Dehalogenase-Catalyzed Epoxide Ring-Opening Reactions.

By performing molecular dynamics (MD), quantum mechanical/molecular mechanical (QM/MM) calculations, and QM cluster calculations, the origin of chemoselectivity of halohydrin dehalogenase (HHDH)-catalyzed ring-opening reactions of epoxide with the nucleophilic reagent NO2- has been explored. Four possible chemoselective pathways were considered, and the computed results indicate that the pathway associated with the nucleophilic attack on the Cα position of epoxide by NO2- is most energetically favorable and has an energy barrier of 12.9 kcal/mol, which is close to 14.1 kcal/mol derived from experimental kinetic data. A hydrogen bonding network formed by residues Ser140, Tyr153, and Arg157 can strengthen the electrophilicity of the active site of the epoxide substrate to affect chemoselectivity. To predict the energy barrier trends of the chemoselective transition states, multiple analyses including distortion analysis and electrophilic Parr function (Pk+) analysis were carried out with or without an enzyme environment. The obtained insights should be valuable for the rational design of enzyme-catalyzed and biomimetic organocatalytic epoxide ring-opening reactions with special chemoselectivity.

Epoxide Ring-Opening Reactions for Abundant Production of Mugineic Acids and Nicotianamine Probes.

A succinct synthetic approach to mugineic acids and 2'-hydroxynicotianamine was established. Unlike all other synthetic methods, this approach utilized epoxide ring-opening reactions to form two C-N bonds and is characterized by the absence of redox reactions. Mugineic acid was synthesized from three readily available fragments on a gram scale in 6 steps. The protected 2'-hydroxynicotianamine was also synthesized in 4 steps, and the dansyl group, serving as a fluorophore, was introduced through a click reaction after propargylation of the 2'-hydroxy group. The dansyl-labeled nicotianamine (NA) iron complexes were internalized by oocytes overexpressing ZmYS1 (from maize) or PAT1 (from human) transporters, indicating successful transport of the synthesized NA-probe through these transporters.

Unveiling a Strategy for Ring Opening of Epoxides: Synthesis of 2-Hydroxyindolinylidenes Using α-Ester Sulfoxonium Ylides.

The untapped potential of α-carbonyl sulfoxonium ylides in epoxide ring-opening reactions has been a notable gap in current research, with such reactivity predominantly associated with the highly reactive dimethylsulfoxonium methylide. This study introduces an innovative approach wherein an epoxide indole, formed in situ from 2-hydroxyindoline-3-triethylammonium bromide, undergoes reaction with α-ester sulfoxonium ylides. The outcome is the efficient synthesis of a range of 2-hydroxyindolin-3-ylidenes, demonstrating favorable yields (41-81%) and Z/E ratios from 4:1 to those of exclusive Z isomers. Additionally, the photophysical properties of the synthesized indolinylidenes are explored, along with their derivatization using various nucleophiles under acid catalysis.

Deciphering the stereo-specific catalytic mechanisms of cis-epoxysuccinate hydrolases producing L(+)-tartaric acid

Microbial epoxide hydrolases, cis-Epoxysuccinate hydrolases (CESHs) have been utilized for commercial production of enantiomerically pure L(+)- and D(-)-tartaric acids for decades. However, the stereo-catalytic mechanism of CESH producing L(+)-tartaric acid (CESH[L]) remains unclear. Herein, the crystal structures of two CESH[L]s in ligand-free, product-complexed, and catalytic intermediate forms were determined. These structures revealed the unique specific binding mode for the mirror-symmetric substrate, an active catalytic triad consisting of Asp-His-Glu, and an arginine providing a proton to the oxirane oxygen to facilitate the epoxide ring-opening reaction, which has been pursued for decades. These results provide the structural basis for the rational engineering of these industrial biocatalysts.

Exploring the synthetic potential of epoxide ring opening reactions toward the synthesis of alkaloids and terpenoids: a review.

Epoxides are oxygen containing heterocycles which are significantly employed as crucial intermediates in various organic transformations. They are considered highly reactive three-membered heterocycles due to ring strain and they undergo epoxide ring opening reactions with diverse range of nucleophiles. Epoxide ring-opening reactions have gained prominence as flexible and effective means to obtain various functionalized molecules. These reactions have garnered substantial attention in organic synthesis, driven by the need to comprehend the synthesis of biologically and structurally important organic compounds. They have also found applications in the synthesis of complex natural products. In this review article, we have summarized the implementation of epoxide ring opening reactions in the synthesis of alkaloids and terpenoids based natural products reported within the last decade (2014-2023).

Synthesis and crystal structure of a new 1D metal–organic coordination polymer with Cu2+ ions based on a chiral terephthalic acid derivative synthesized for the first time

A new chiral 1D coordination polymer was synthesized starting from novel l-prolylamino substituted terephthalic acid and evaluated in enantioselective epoxide ring opening reaction.

Regioselective synthesis of 3,4-diarylpyrimido[1,2-b]indazole derivatives enabled by iron-catalyzed ring-opening of styrene oxides.

The first synthesis of 3,4-diarylpyrimido[1,2-b]indazole derivatives from 3-aminoindazoles has been realized. The FeCl3-catalyzed intermolecular epoxide ring-opening reaction altered the order of annulation, with the free primary NH2 groups in 3-aminoindazoles preferentially reacting with styrene oxides instead of aromatic aldehydes. This protocol is further highlighted by its broad substrate compatibility, high chemo- and regioselectivities, and the late-stage modifications of bioactive molecules. Without aromatic aldehydes, the synthesis of 3-aryl-4-acylpyrimido[1,2-b]indazole derivatives can also be accomplished using alternative reaction conditions.

Non-enzymatic synthesis of C-methylated fluostatins: discovery and reaction mechanism.

Two C-methylated fluostatins (FSTs) B3 (1) and B4 (2) were synthesized from flavin-mediated nonenzymatic epoxide ring-opening reactions of FST C. The structures of 1 and 2 were elucidated by HRESIMS, NMR, and ECD spectroscopic analyses. A subsequent 13C labeling study demonstrated that the C-methyl groups of 1 and 2 were derived from DMSO and enabled the mechanistic proposal of a nonenzymatic C-methylation.

Synthesis, spectroscopic characterizations, DFT calculations and molecular docking studies of new quinoline-oxirane/piperidine/morpholine hybrids from quinoline gem‑dicyanoepoxide

We report in this paper a combined experimental and theoretical study of new 2-quinolone-piperidine (5a) and -morpholine (5b-c) hybrids from3-(2-chloroquinolin-3-yl) oxirane-2,2-dicarbonitrile (3) via an epoxide ring opening reaction using appropriate synthetic routes. In a parallel approach, a tandem consecutive process was carried out, without isolation of the brominated intermediate for the synthesis of 2-quinolone-morpholine (5c). The prepared compounds were fully characterized by conventional analytical techniques, and single-crystal X-ray diffraction for compound 5c was also reported. To increase the accuracy of experimental results, DFT and TD-DFT calculations were performed including molecular structure optimization, NMR, optical and electronic data, frontier molecular orbitals and molecular descriptors. In addition, a molecular docking calculation was carried out to estimate the affinity between compounds 3, 5a, 5b and 5c and Acetylcholinesterase (AChE)/ Butyrylcholinesterase (BuChE). Theoretical results are in agreement with the experimental.

Chemical Tailoring of β-Cyclodextrin-Graphene Oxide for Enhanced Per- and Polyfluoroalkyl Substances (PFAS) Adsorption from Drinking Water.

We report on the synthesis of β-cyclodextrin (βCD) modified graphene oxide (GO) nanosheets, having different sized alkyl linkers (GO-Cn -βCD) and their exploitation as sorbent of per- and polyfluoroalkyl substances (PFAS) from drinking water. βCD were functionalized with a pending amino group, and the resulting precursors grafted to GO nanosheets by epoxide ring opening reaction. Loading of βCD units in the range 12 %-36 % was estimated by combined XPS and elemental analysis. Adsorption tests on perfluorobutanoic acid (PFBA), a particularly persistent PFAS selected as case study, revealed a strong influence of the alkyl linker length on the adsorption efficiency, with the hexyl linker derivative GO-C6 -βCD outperforming both pristine GO and granular activated carbon (GAC), the standard sorbent benchmark. Molecular dynamic simulations ascribed this evidence to the favorable orientation of the βCD unit on the surface of GO which enables a strong contaminant molecules retention.

In vitro cytotoxic effect of stigmasterol derivatives against breast cancer cells

BackgroundStigmasterol is an unsaturated phytosterol that belong to the class of tetracyclic steroids abundant in Rhoicissus tridentata. Stigmasterol is an important constituent since it has shown impressive pharmacological effects such as anti-osteoarthritis, anticancer, anti-diabetic, anti-inflammatory, antiparasitic, immunomodulatory, antifungal, antioxidant, antibacterial, and neuroprotective activities. Furthermore, due to the presence of π system and hydroxyl group, stigmasterol is readily derivatized through substitution and addition reactions, allowing for the synthesis of a wide variety of stigmasterol derivatives.MethodsStigmasterol (1) isolated from Rhoicissus tridentata was used as starting material to yield eight bio-active derivatives (2–9) through acetylation, epoxidation, epoxide ring opening, oxidation, and dihydroxylation reactions. The structures of all the compounds were established using spectroscopic techniques, NMR, IR, MS, and melting points. The synthesized stigmasterol derivatives were screened for cytotoxicity against the hormone receptor-positive breast cancer (MCF-7), triple-negative breast cancer (HCC70), and non-tumorigenic mammary epithelial (MCF-12 A) cell lines using the resazurin assay.ResultsEight stigmasterol derivatives were successfully synthesized namely; Stigmasterol acetate (2), Stigmasta-5,22-dien-3,7-dione (3), 5,6-Epoxystigmast-22-en-3β-ol (4), 5,6-Epoxystigmasta-3β,22,23-triol (5), Stigmastane-3β,5,6,22,23-pentol (6), Stigmasta-5-en-3,7-dion-22,23-diol (7), Stigmasta-3,7-dion-5,6,22,23-ol (8) and Stigmast-5-ene-3β,22,23-triol (9). This is the first report of Stigmasta-5-en-3,7-dion-22,23-diol (7) and Stigmasta-3,7-dion-5,6,22,23-ol (8). The synthesized stigmasterol analogues showed improved cytotoxic activity overall compared to the stigmasterol (1), which was not toxic to the three cell lines tested (EC50 ˃ 250 µM). In particular, 5,6-Epoxystigmast-22-en-3β-ol (4) and stigmast-5-ene-3β,22,23-triol (9) displayed improved cytotoxicity and selectivity against MCF-7 breast cancer cells (EC50 values of 21.92 and 22.94 µM, respectively), while stigmastane-3β,5,6,22,23-pentol (6) showed improved cytotoxic activity against the HCC70 cell line (EC50: 16.82 µM).ConclusionNatural products from Rhoicissus tridentata and their derivatives exhibit a wide range of pharmacological activities, including anticancer activity. The results obtained from this study indicate that molecular modification of stigmasterol functional groups can generate structural analogues with improved anticancer activity. Stigmasterol derivatives have potential as candidates for novel anticancer drugs.

“Tai Chi” philosophy driven dual-network ionogel membrane comprised of ionic guests in a multifunctional host for propylene/propane separation

Facilitated transport ionogel membranes have shown great prospects in propylene/propane separation due to the stability of carrier media, no leakage, and promising thermal/physical properties. In the present study, inspired by the Tai Chi philosophy of adjusting inorganic and organic features, a dual-network ionogel was made of multi-functional organosilane, [EMIM][TFSI] ionic liquid, AgBF4, and catalysts. An effective strategy, including solvent-free solvolytic sol-gel and epoxide ring-opening reaction, was proposed to keep the inorganic/organic balance and obtain ionogel films with high IL loading (up to 82%) and self-standing. The ionogels were characterized by a phase diagram, formation mechanism, FTIR, N2 adsorption-desorption isotherms, TGA, SEM, mechanical properties, and transport properties. The Multifunctional host induced the breaking of bondage between the components of IL electrolyte (AgBF4 and IL); thereby more free Ag+ ions become available for facilitating the olefin transport. A computational molecular approach was applied to better understand the possible interactions between the ionic guest and multifunctional host. Results indicate that the optimized ionogel not only has excellent transport properties (C3H6 permeability of 243.1 Barrer and C3H6/C3H8 selectivity of 20.2) but also has desirable mechanical and thermal properties. The synthesis of ionogel based on Tai Chi philosophy opens a new window for facilitated transport of gas separation membranes.

Selective Synthesis of Monofluorinated Compounds Applying Amine/HF Reagents.

For nucleophilic monofluorination, amine/HF reagents such as Et3 N⋅3HF, Pyr⋅9HF (Olah's reagent) and similar combinations belong to the most frequently used fluoride sources, whereupon the selectivity of these reagents can be very different depending of its acidity, the nucleophilicity of the fluoride equivalent, and the structure of the particular substrate. These reagents can be used safely in ordinary chemistry laboratories for nucleophilic substitution reactions by fluoride at sp3 -hybridized carbon centers. For ring opening reactions of epoxides, the regio- and stereoselectivity is very much depending of the nature of the epoxide and the acidity of the HF reagent favoring either SN 1 or SN 2 type reactions. Similarly, the outcome of halofluorination and similar reactions with sulfur or seleno electrophiles can be controlled by the particular combination of the electrophile and the fluoride source. Examples for the application of these reaction types for the synthesis of fluorine-containing analogues of natural products or biologically relevant compounds are in the focus of this personal account.

Synthesis, Characterization, and Catalytic Reactivities of Novel Dinuclear Cu(II) Complexes : Efficient Ring Opening Reaction of Epoxide

Synthesis, Characterization, and Catalytic Reactivities of Novel Dinuclear Cu(II) Complexes : Efficient Ring Opening Reaction of Epoxide