Acetoxy Research Articles

Radical-triggered translocation of C-C double bond and functional group.

Multi-site functionalization of molecules provides a potent approach to accessing intricate compounds. However, simultaneous functionalization of the reactive site and the inert remote C(sp3)-H poses a formidable challenge, as chemical reactions conventionally occur at the most active site. In addition, achieving precise control over site selectivity for remote C(sp3)-H activation presents an additional hurdle. Here we report an alternative modular method for alkene difunctionalization, encompassing radical-triggered translocation of functional groups and remote C(sp3)-H desaturation via photo/cobalt dual catalysis. By systematically combining radical addition, functional group migration and cobalt-promoted hydrogen atom transfer, we successfully effectuate the translocation of the carbon-carbon double bond and another functional group with precise site selectivity and remarkable E/Z selectivity. This redox-neutral approach shows good compatibility with diverse fluoroalkyl and sulfonyl radical precursors, enabling the migration of benzoyloxy, acetoxy, formyl, cyano and heteroaryl groups. This protocol offers a resolution for the simultaneous transformation of manifold sites.

Ethyl 2-[(2-oxo-2H-chromen-6-yl)oxy]acetate

Ethyl 2-[(2-oxo-2H-chromen-6-yl)oxy]acetate, C13H12O5, a member of the pharmacologically important class of coumarins, crystallizes in the monoclinic C2/c space group in the form of sheets, within which molecules are related by inversion centers and 21 axes. Multiple C—H...O weak hydrogen-bonding interactions reinforce this pattern. The planes of these sheets are oriented in the approximate direction of the ac face diagonal. Intersheet interactions are a combination of coumarin system π–π stacking and additional C—H...O weak hydrogen bonds between ethyl acetoxy groups.

A new labdane diterpenoid, in vitro and in silico cytotoxicity, and protease inhibitory effects of phytochemicals from Juniperus polycarposK. Koch leaves

Cytotoxicity-guided purification of Juniperus polycarpos K. Koch leaves (Cupressaceae) led to the isolation of a new labdane diterpenoid, 3-(acetyloxy)-acetylisocupressic acid (1), together with isocupressic acid (2), 3,4-dimethoxycinnamoyl alcohol (3) and deoxypodophyllotoxin (4). The chemical structures of 1–4 were established by detailed 1D and 2D NMR, HRFAB-MS and LRESI-MS, as well as by comparing the spectral data with those reported in the literature. Compound 1 was ineffective against HepG2 cells and protease enzyme, while 2 showed potent cytotoxicity against HepG2 cells (IC50 of 3.73 μg/mL) compared to cisplatin (IC50 of 12.65 μg/mL). Computational analyses with CDK1 protein (a prominent protein in the cell cycle of HepG2 cells) revealed the binding affinity of 2 (–31.86 kcal/mol) was better than 1 (–19.70 kcal/mol) because the acetoxy groups did not allow binding deeply to the ATP binding site. Compounds 2 and 4 moderately inhibited the protease activity (IC50 = 52.7 and 63.0 μg/mL, respectively). Further in vitro and in vivo studies on the plant are strongly recommended.

Reaction-induced liquid crystalline polybenzoxazine thermosets using aryl ester bonds as cross-linkages

ABSTRACT The increasing tendency to develop integration in electronic devices lead to the demand for thermally conductive polymeric materials. We offered a simple synthetic route to thermally conductive polybenzoxazine thermosets bearing liquid crystalline structures without the addition of any filler. Benzoxazine monomer of BZ-COOH was synthesized via Mannich reaction of p-hydroxy benzoic acid, p-formaldehyde, and dodecyl amine. After ring-opening polymerization of BZ-COOH, the obtained benzoxazine oligomer of OBZ-COOH was converted into acetoxy-bearing benzoxazine oligomer of OBZ-AC. Through self-crosslinking reaction of acetoxy group and carboxyl group in OBZ-AC using Zn(CH3COO)2 as a catalyst, the polybenzoxazine thermosets of OBZ-PES were produced. The liquid crystalline behavior of OBZ-AC was studied by POM, SAXS, and DSC. The results show that OBZ-AC formed the LC mesophase during isothermal and non-isothermal curing. The LC mesophase displays a layered arrangement of the smectic C phase. The formation mechanism is esterification reaction-induced. Owing to the formation of liquid crystalline structure, the TC of OBZ-PES is found to be 0.284 W/m. K, which is 21% and 16% greater than those of OBZ-COOH and OBZ-AC, respectively. In addition, the OBZ-PES shows excellent thermal performance. Its Tg(G”) is up to 269°C. Its 5% weight loss temperature (Td5) and 10% weight loss temperature (Td10) are 383°C and 410°C, respectively.

First principles study of 2-(acetoxy group)benzoic acid under different extremely high-pressure environments

Based on Density Functional Theory (DFT), a first-principles study was conducted on the crystal structure, electronic structure, and optical properties of the organic material 2-(acetoxy group) benzoic acid crystal (C9H8O4) under extremely high pressure ranging from 0 to 300 GPa. The structure study revealed the significant bonding and bond breaking phenomena at pressures of 80 GPa and 270 GPa, respectively, indicating that it may induced the lattice phase transitions. The energy band analysis demonstrated that the crystal underwent a transition from a direct bandgap semiconductor at 0 GPa to an indirect bandgap semiconductor at 80 GPa, and then at 270 GPa, the crystal exhibited a metallic phase with a bandgap of 0. The density of states (DOS) provided evidence that this crystal undergo intricate phase transitions under extremely high pressure. The optical properties were further compared and analyzed. It was observed that the peak of optical absorption shifted towards higher energy regions, while the peak of photoconductivity and Loss function shifted towards the blue shift. These findings indicate that extremely high pressures can effectively modulate the structure and properties of C9H8O4 material. This research offers valuable insights for further exploration of the properties of C9H8O4 materials and their potential applications in organic optoelectronic devices.

Synthesis, cytotoxicity, and antibacterial studies of 2,4,5,6-substituted hexahydro-1H-isoindole-1,3(2H)-dione.

In this study, synthesis of novel isoindole-1,3-dione analogues bearig halo, hydroxy, and acetoxy groups at the position 4,5,6 of the bicyclic imide ring was performed to examine their potential anticancer effects against some cell lines. A multistep chemical pathway was used to synthesize the derivatives. The cytotoxic effect of trisubstituted isoindole derivatives were evaluated by determining cellular viability using the MTT assay against A549, PC-3, HeLa, Caco-2, and MCF-7 cell lines. The C-2 selective ring-opening products were obtained from the ring-opening reaction of 5-alkyl/aryl-2-hydroxyhexahydro-4H-oxireno[2,3-e]isoindole-4,6(5H)-diones with nucleophiles such as chloride (Cl- ) and bromide (Br- ) ions. In addition, the ring-opening products halodiols were converted to their related acetates. The anticancer activity of synthesized isoindole-1,3-dione derivatives was investigated against HeLa, A549, MCF-7, PC3, and Caco-2 cells in vitro and resulted in varies cytotoxic effect depend on the group attached to the isoindole molecule. Furthermore, the evaluation of the antimicrobial action of trisubstituted isoindole derivatives against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria was assessed and found out selective inhibition of the both bacterial growth via different trisubstituted isoindole derivatives. The results of this work encourage further research on the potential utilization of trisubstituted isoindole derivatives as cytotoxic and antimicrobial agents.

Mo-catalyzed Friedel-Crafts alkylation using alkenes under mild condition

Mo-catalyzed hydroarylation of alkenes can be achieved at room temperature. The procedure can perform by using electron rich arenes, and the corresponding product is obtained regioselectively as a mixture of para- and ortho-isomers in good yield. Both aryl alkenes and aliphatic alkenes are available in the procedure. On the other hand, a reaction of allylic acetates gives the corresponding allyl arenes via leaving of acetoxy group.

Natural tourmaline activated peracetic acid for efficient degradation of sulfadiazine: Reaction mechanisms and catalyst reusability

Peracetic acid (PAA) has received extensive attention in the water treatment due to its high oxidation potential and low toxicity of by-products. In this study, natural non-toxic mineral tourmaline (TM) was used to activate PAA to remove sulfadiazine (SDZ). The TM/PAA system could remove 92 ​% SDZ in 120 ​min. The radical analysis confirmed the co-existence of both free radical and non-free radical degradation pathways in the TM/PAA system, indicating that singlet oxygen (1O2) and acetyl(per)oxy radicals (CH3C(O)O· and CH3C(O)OO·) were the main reactive oxygen species. The Fe2+/Fe3+ ratio on the TM surface decreased during the degradation of SDZ due to Fe2+ consumption. The effect of water matrix on SDZ removal indicated that Cl−, SO42− and NO3− posed little effect on SDZ removal, while CO32− inhibited SDZ removal by affecting pH. Particularly, humic acid (HA) slightly promoted SDZ removal. Ten by-products of SDZ were identified by HPLC-MS/MS, and four possible transformation pathways (SO2 detachment, S–N breakage, amino acid oxidation, and hydroxylation) were proposed. TM was recycled five times and the removal of SDZ remained above 85 ​%, confirming its excellent reusability. This work indicates the TM/PAA system is of great potential for the application on the organic contaminant removal.

Chiral covalent organic framework incorporated organic polymer monolithic capillary column for enantioseparations.

A chiral covalent organic framework was synthesized, characterized, and incorporated into organic polymer monolithic capillary columns to provide chiral stationary phases for enantioseparations. The prepared monolithic capillary columns were characterized by scanning electron microscopy and elemental analysis. To obtain better enantioseparations, the columns' preparation conditions, and enantioseparation conditions were optimized. Baseline resolutions of several chiral compounds were obtained with good reproducibility and stability. Furthermore, the mechanism of chiral recognition was investigated using molecular docking with AutoDock. Docking results showed that the enantioselectivity factor rather than resolution is correlated with the binding free energy difference between enantiomers with the chiral covalent organic framework. And abundant acetoxy and nitrile groups as well as benzene rings in the chiral covalent organic framework are responsible for the enantioseparation ability of the chiral monolithic capillary columns.

An unexpected acid-catalyzed rearrangement of diacetoxy benzylidenespirostanes to spirochromene acetals and spiroindenes with radical scavenger activity

23E-diacetoxybenzylidenespirostanes underwent rearrangement when treated with HCl in CH2Cl2/CH3OH. The course of the rearrangement depends on the substitution pattern in the phenyl ring. While compounds bearing an acetoxy group at the ortho position produced spirochromenes, the partners with no substituent at the ortho position led to spiroindenes. All the rearranged compounds exhibited moderate antioxidant activity.

Abiotic transformation of synthetic progestins in representative soil mineral suspensions

Altrenogest (ALT), drospirenone (DRO), and melengestrol acetate (MLA) are three highly potent synthetic progestins that can be released into agricultural soils, while their fate in soil minerals remains unclear. This study explored the transformation of these progestins in MnO2, SiO2, and ferrihydrite suspensions and identified their transformation products (TPs) via high resolution mass spectrometry and density functional theory calculations. Transformations were only observed for DRO and MLA in SiO2 suspension and ALT in MnO2 suspension (half-lives = 0.86 min – 9.90 day). ALT transformation was facilitated at higher MnO2 loadings, while DRO and MLA transformations were inhibited at higher SiO2 loadings. These data indicated that hydrophobic partitioning interaction was dominant at higher SiO2 loadings rather than specific interaction, which limited subsequent surface-catalyzed transformation. ALT transformation rate decreased with increasing pH because MnO2 reduction requires proton participation. In contrast, relatively high pH facilitated MLA and DRO transformation, indicating that base-catalyzed hydrolysis occurred in SiO2 suspension. The clustermap demonstrated the formation of abundant TPs. Lactone ring and acetoxy group hydrolysis was the major transformation pathway for DRO and MLA, with estimated yields of 57.7% and 173.2% at 6 day, respectively. ALT experienced C12 hydroxylation and formed the major TP 326g (yield of 15.4% at 8 hr). ALT also experienced allyl group oxidation and subsequent C5 hydroxylation, forming the major TP 344a (yield of 14.1% at 8 hr). This study demonstrates that TPs of metastable progestins are likely the main species in soils and that TP identification is a particular priority for risk assessment.

Solvent free sol-gel based synthesis of soft magnesium silicate

In this study, soft magnesium silicates were prepared via sol-gel method starting from diethylphosphatoethyltriethoxysilane (SiP), magnesium ethoxide and magnesium acetate. The thermal reaction of the different systems without any solvent was studied by a thermogravimetric analysis coupled to gas chromatography and mass spectroscopy in order to identify the volatile by-products and then suggest a reaction mechanism. The identification of several by-products formed during the reactions evidenced a non-hydrolytic sol-gel based route between the ethoxy and acetoxy groups of magnesium ethoxide and magnesium acetate respectively with the ethoxy groups of SiP. In addition, X-ray photoelectron spectroscopy analyses highlighted the creation of Mg–O–Si bonds. The viscoelastic behavior of the reactive systems allowed to confirm the formation of the network but also the determination of the gelation time. It corresponded respectively to 2150 and 1020 s for the reaction between magnesium ethoxide and SiP and magnesium acetate and SiP carried out at 170 °C. All these data confirm the formation of a “soft” inorganic network in that range of temperature. The graphical abstract represents first a schematic view of the studied reactions. The graph on the bottom-left corner shows the deconvolution of high resolution XPS spectra in the Mg (1s) region of MgOEt + SiP system treated at 450 °C. On the bottom-right corner, the evolution of tan (δ) at 170 °C under air during time sweeps at 1, 2, 3, and 5 rad/s for MgOEt + SiP system is presented.

Highly (E)-Selective Trisubstituted Alkene Synthesis by Low-Valent Titanium-Mediated Homolytic Cleavage of Alcohol C-O Bond.

Ti-mediated homolytic C-O bond cleavage was useful for cascade radical-ionic reactions. Benzyl alcohols treated with TiCl4(col) (col = 2,4,6-collidine) and Mn powder generated the corresponding benzyl radicals; in addition, their reaction with 2-carboxyallyl acetates and the subsequent elimination of the acetoxy group yielded α,β-unsaturated carbonyl compounds with exclusive (E)-stereoselectivity. The simplicity of the procedure and its wide substrate scope represent a solution to the drawbacks associated with the reactions.

Synthesis and oxidative transformations of 2-functionalized 2-trifluoromethyltetrahydrothiophenes

2-Acetoxymethyl- and 2-hydroxymethyl-2-(trifluoromethyl)tetrahydrothiophenes have been prepared from readily obtainable 3-hydroxy-3-(trifluoromethyl)tetrahydropyran by its reactions of sulfur-assisted ring contraction. With the aim to explore the synthetic utility of new fluorinated tetrahydrothiophenes and to estimate the influence of trifluoromethyl group on their reactivity, various types of the oxidative transformations, involving oxidation and oxoimination of sulfur atom, oxidation of hydroxymethyl group and chlorination of free α-position to sulfur atom, were studied. Large sterical demand of CF3 group has been revealed from the stereochemical outcome of the oxidation and oxoimination of the sulfur atom. Electron withdrawing properties of CF3 group are evident from low susceptibility of 2-hydroxymethyl-(trifluoromethyl)tetrahydrothiophene to the oxidation of hydroxymethyl group and from low activity of 2-acetoxymethyl-5-chloro-2-(trifluoromethyl)tetrahydrothiophene in nucleophilic substitution and dehydrochlorination reactions. Convenient protocols for the preparation of trifluoromethylated tetrahydrothiophenes with sulfoxide, sulfone, sulfoximino, aldehyde and carboxy functionalities, acetoxy group in the position 5 of the heterocycle, and 2-(acetoxymethyl)-2-(trifluoromethyl)-2,3-dihydrothiophene have been developed. The results of these studies demonstrate that 2-acetoxymethyl- and 2-hydroxymethyl-2-(trifluoromethyl)tetrahydrothiophenes are useful precursors to a variety of new small fluorinated molecules.

Protecting‐Group‐Free One‐Step Palladium‐Catalyzed Coupling on C25 of Cucurbitacin B Expands Chemical Diversity with Improved Cytotoxicity against A549 Cells

Comprehensive SummaryThe natural product cucurbitacin B has been widely studied because of its multiple biological activities, especially its potent antitumor effects. However, modifications of cucurbitacin B are mainly focused on the C2 and C16 site, studies on the C25 acetoxy group are still limited. We successfully developed a palladium‐catalyzed allylic coupling of cucurbitacin B with boronic acids, providing a one‐step approach to expand the chemical diversity of the C25 position. Our method was protecting‐group‐free, showing a good functional group tolerance and a wide substrate scope under mild reaction conditions. A library of 29 derivatives was prepared, compounds 2q and 2u showed higher cytotoxicity against A549 cells than cucurbitacin B, compounds 2n and 2o maintained potency, and the introduced hydroxyl and amino groups could be further derived.

Design of 1‐(2‐pyrrolidinone)‐butane‐1,3‐dione derivatives and acetoxylation of these compound's methylene via hypervalent iodine (III)

AbstractAn interesting synthesis method for 2‐acetate‐1‐(2‐pyrrolidinone)‐butane‐1,3‐dione compounds was developed in this work. The synthesis of these compounds was carried out in three steps. In the first step, 2‐pyrrolidone derivatives were obtained by the Friedel‐Crafts reaction in presence of Eaton's reagent. Then, ‐NH group of 2‐pyrrolidone compounds were attached acetoacetate group in presence of 2,6‐trimethyl‐4H‐1,3‐dioxin‐4‐one reagent. Lastly, 1‐(2‐pyrrolidinone)‐butane‐1,3‐dione derivatives were reacted with Pida to attach acetoxy group to these compound's methylene.

Monosubstituted Coumarins Inhibit Epinephrine-induced Platelet Aggregation.

AimThe aim of this study was to evaluate the in vitro effect of coumarin and 15 monosubstituted derivatives on the inhibition of human platelet aggregation induced by various pro-aggregatory agonists, particularly by epinephrine.BackgroundThe emergence of residual platelet reactivity during the use of conventional antiplatelet agents (acetylsalicylic acid and clopidogrel) is one of the main causes of double therapy´s therapeutic failure. Platelet adrenoceptors participate in residual platelet reactivity. Therefore, it is necessary to develop new antiplatelet agents that inhibit epinephrine-induced platelet aggregation as a new therapeutic strategy. Information on the antiplatelet activity of coumarins in inhibiting epinephrine-induced aggregation is limited.Objective The objective of this study was to establish the structure-activity relationship (SAR) of coumarin derivatives with hydroxy, methoxy, and acetoxy groups in different positions of the coumarin nucleus to identify the most active molecules. Moreover, this study aimed to use in silico studies to suggest potential drug targets to which the molecules bind to produce antiplatelet effects.MethodsThe platelet aggregation was performed using a Lumi-aggregometer; the inhibitory activity of 16 compounds were evaluated by inducing the aggregation of human platelets (250 × 103/μl) with epinephrine (10 µM), collagen (2 µg/ml) or ADP (10 µM). The aggregation of control platelets was considered 100% of the response for each pro-aggregatory agonist.ResultsEleven molecules inhibited epinephrine-induced aggregation, with 3-acetoxycoumarin and 7-methoxycoumarin being the most active. Only coumarin inhibited collagen-induced platelet aggregation, but no molecule showed activity when using ADP as an inducer.Conclusions In silico studies suggest that most active molecules might have antagonistic interactions in the α2 and β2 adrenoceptors. The antiplatelet actions of these coumarins have the potential to reduce residual platelet reactivity and thus contribute to the development of future treatments for patients who do not respond adequately to conventional agents.

Newly described antioxidant disecolactonic ergosteroids from marine cuttlefish Sepia pharaonis: Pharaonoids A-B as prospective carbohydrate digestive enzyme inhibitors

Biochemical investigation of crude solvent extract of pharaoh cuttlefish Sepia pharaonis (family Sepiidae) led to the isolation of two undescribed disecolactonic ergosteroids, pharaonoids A-B. The compounds were characterized as 11β-acteoxy-7α-hydroxy-19-Nor-1,10:9,10-disecoergosta-3-ene-61-oxa-1-one (pharaonoid A) and 11β-hydroxy-19-Nor-1,10:9,10-disecoergosta-3-ene-61-oxa-1-one (pharaonoid B) in conjunction with spectroscopic analysis encompassing one and two-dimensional nuclear magnetic resonance and mass spectrometric analyses. Pharaonoid A, bearing an acetoxy and hydroxyl groups, respectively at C-11 and C-7 positions exhibited considerably greater inhibition potential against carbohydrate hydrolysing enzymes α-amylase (IC50 1.14 mM) and α-glucosidase (IC50 1.23 mM) than those displayed by pharaonoid B (IC50 1.49/1.38 mM), and was proportionate with those exhibited by standard drug acarbose (IC50 0.60 and 0.40 mM, respectively), thereby recognizing the anti-hyperglycemic potential of pharaonoid A. Promising anti-oxidant property for pharaonoid A (IC50 ∼ 1 mM) could conceivably corroborate its attenuation potential against carbohydrate digestive enzymes. Greater electronic parameters along with optimum lipophilic-hydrophobic balance of pharaonoid A were directly corroborated to the anti-carbolytic properties occurring via transcellular mechanism. Greater binding energies (−9.50 kcal mol−1) and inhibition constant (Ki 48.21 nM) at the active site of α-amylase enzyme were displayed by pharaonoid A than those exhibited by its B analogue. Promising bioactive properties of the disecolactonic steroids isolated from the marine pharaoh cuttlefish are anticipated to be utilized as functional food components and potential nutraceuticals against oxidative stress and hyperglycemic disorders.

Efficient pilot-scale synthesis of the key cefonicid intermediate at room temperature

Abstract Cefonicid is a common second-generation cephalosporin, and the 7-amino-3-[sulphomethyl-1-H-tetrazol-5-yl-thiomethyl]-3-cephem-4-carboxylate monosodium salt is a key synthetic intermediate in its preparation. Despite the considerable international demand for this antibiotic, its preparation is hampered by low synthetic yield, long reaction time, and time-consuming industrial filtration over charcoal after the purification step. In the context of the industrial production of pharmaceutical intermediates, in which the balance between streamlining and enhancing productivity is necessary in order to compete in the global active pharmaceutical ingredients (API) market, we have investigated an efficient and practical procedure for the synthesis of a key cefonicid intermediate that features a telescopic route whose synthetic steps are all performed at room temperature; from the displacement of the acetoxy group with boron trifluoride to crystallization without treatment with charcoal. In other words, a simpler, scalable, cost-effective and energy-saving protocol is herein reported as a means of moving towards commercial manufacturing. The optimization of the process parameters and the industrial-scale impact assessment should pave the way for industrialization.

Resorcinarene-Based Supramolecular Capsules: Supramolecular Functions and Applications

AbstractA resorcinarene is a synthetic macrocycle consisting of four resorcinol molecules covalently linked by methylene bridges. The interannular bridges produce a cavitand that has a bowl-shaped structure. We have developed supramolecular capsules through Ag(I) or Cu(I) coordination-driven self-assembly of cavitands possessing 2,2′-bipyridyl arms in their upper rims. The self-assembled capsules accommodate various molecular guests and supramolecular assemblies possessing acetoxy groups. The host–guest chemistry of the molecular capsules has been applied in the fabrication of supramolecular polymers. This account describes recent developments in the supramolecular chemistry of resorcinarene-based coordination capsules and provides a brief history of resorcinarene-based capsules and related capsules.