Month: November 2022

Structure-activity relationship of novel (benzoylaminophenoxy)phenol derivatives as anti-prostate cancer agents was written by Kazui, Yuko;Fujii, Shinya;Yamada, Ayumi;Ishigami-Yuasa, Mari;Kagechika, Hiroyuki;Tanatani, Aya. And the article was included in Bioorganic & Medicinal Chemistry in 2018.Application of 103-16-2 The following contents are mentioned in the article:

The androgen receptor (AR) is a ligand-inducible transcription factor belonging to the nuclear receptor superfamily, and is a target mol. for development of drugs to treat prostate cancer. However, AR antagonists in clin. use, such as flutamide (3a) and bicalutamide (4), encounter resistance after several years of hormone therapy, predominantly due to mutations of AR. Thus, although some new-generation AR antagonists have been developed, novel types of AR antagonists are still required to treat drug-resistant prostate cancer. We previously reported a novel (benzoylaminophenoxy)phenol derivative 10a, which is structurally distinct from conventional AR antagonists. Here, we systematically examined the structure-activity relationship of (benzoylaminophenoxy)phenol derivatives on the inhibitory activity on the prostate cancer cell proliferations. We found that the 4-[4-(benzoylamino)phenoxy]phenol backbone is important for anti-prostate cancer activity. Introduction of a small substituent at the 2 position of the central benzene ring (B ring) increases the activity. Among the synthesized compounds, 19a and 19b exhibited the most potent inhibitory activity toward dihydrotestosterone-induced proliferation of several androgen-dependent cell lines, SC-3 (wild-type AR), LNCaP (T877A AR), and 22Rv1 (H874Y AR), but interestingly also inhibited proliferation of AR-independent PC-3 cells. These compounds, which have a different pharmacophore from conventional AR antagonists, are promising drug candidates for the treatment of prostate cancer. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Application of 103-16-2).

4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is γ-valerolactone.Application of 103-16-2

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Focus on Olea europaea L. pruning by-products: extraction techniques, biological activity, and phytochemical profile was written by Faraone, Immacolata;Russo, Daniela;Bruno, Maria Roberta;Todaro, Luigi;D′Auria, Maurizio;Milella, Luigi. And the article was included in Biofuels, Bioproducts & Biorefining in 2021.COA of Formula: C9H12O3 The following contents are mentioned in the article:

The Olea europaea L. tree has played a central role in Mediterranean culture since ancient times. Several studies have highlighted the health-promoting properties both of its primary products (olives) and its byproducts (leaves, pomace, husk, stone, mill wastes, and wood). In this study, pruning residues from 25-yr-old olive trees located in a Mediterranean region (Basilicata, Italy) were analyzed. The antioxidant activity of hydro-alc. extracts from wood samples were analyzed through three complementary in vitro assays. The mol. composition of the extracts was thoroughly evaluated using a gas chromatog. apparatus coupled with a mass spectrometer (GC-MS). Our study demonstrated that all but three extracts had remarkable antioxidant activity, which was likely due to the meaningful presence of phenolic compounds, mostly derived from lignin. Moreover, the results showed that bark extracts obtained with ultrasound-assisted extraction (UAE) had the highest antioxidant activity. In this extract, several known compounds with demonstrated antioxidant activity were found, including hexylresorcinol, 1-methyl-N-vanillyl-2-phenethamine, and allopurinol. This research suggests that woody olive byproducts are a potential natural resource of antioxidants. These compounds could be useful for functional foods and in industry, and could help to solve the problem of pruning residues, increasing their potential economic value. 2021 The Authors. Biofuels, Bioproducts and Biorefining published by Society of Industrial Chem. and John Wiley & Sons Ltd. This study involved multiple reactions and reactants, such as 4-Hydroxy-3-methoxyphenethanol (cas: 2380-78-1COA of Formula: C9H12O3).

4-Hydroxy-3-methoxyphenethanol (cas: 2380-78-1) belongs to ethers. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Esters contain a carbonyl center, which gives rise to 120° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. COA of Formula: C9H12O3

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Effective ultrasonic-assisted extraction and solubilization of curcuminoids from turmeric by using natural deep eutectic solvents and imidazolium-based ionic liquids was written by Shekaari, Hemayat;Zafarani-Moattar, Mohammed Taghi;Mokhtarpour, Masumeh. And the article was included in Journal of Molecular Liquids in 2022.SDS of cas: 33171-05-0 The following contents are mentioned in the article:

Curcuminoids (CURs), bioactive and antioxidant polyphenols, are major components of turmeric. Com. available component in CURs are curcumin (C) as the main constituent and the other two demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) as minor components. Extraction and anal. of these components from turmeric may pose specific challenges and yield different results. The organic solvents applied in traditional solvent extraction systems are not eco-friendly owing to their properties such as flammability, toxicity and volatility. For this reason, in this research work, ten deep eutectic solvents (DESs) and three ionic liquids (ILs) were selected to investigate the extraction of CURs from turmeric. Further, DES and ILs-based extraction was performed under ultrasound. Under extraction conditions, the CURs in the turmeric powder was measured by the use of high performance liquid chromatog. (HPLC). The maximum CURs amount of 164.51 mg/g was attained using effective ultrasound-assisted extraction in 50% water content DES or IL at 5% solid loading with 50.8 W/cm2 power intensity at 363 K in 60 min. This improved extraction method can be economical, green and effective alternative to conventional solvent extraction for CURs. On the other hand, the solubility of standard CUR was obtained at 298.15 K using saturation shake flask method. Finally, Hansen solubility parameters (HSP) were applied to identify solvents which were compatible with CURs. All the results were consistent with each other, supporting the validity of our extraction method. This study involved multiple reactions and reactants, such as Bisdemethoxycurcumin (cas: 33171-05-0SDS of cas: 33171-05-0).

Bisdemethoxycurcumin (cas: 33171-05-0) belongs to ethers. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Polyesters are important plastics, with monomers linked by ester moieties. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.SDS of cas: 33171-05-0

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Identification of p53 Activators in a Human Microarray Compendium was written by Corton, J. Christopher;Witt, Kristine L.;Yauk, Carole L.. And the article was included in Chemical Research in Toxicology in 2019.Application In Synthesis of 4-Benzyloxyphenol The following contents are mentioned in the article:

Biomarkers predictive of mol. and toxicol. effects are needed to interpret emerging high-throughput transcriptomic data streams. The previously characterized 63 gene TGx-DDI biomarker that includes 20 genes known to be regulated by p53 was previously shown to accurately predict DNA damage in chem.-treated cells. The authors comprehensively evaluated whether the mol. basis of the DDI predictions was based on a p53-dependent response. The biomarker was compared to microarray data in a compendium derived from human cells using the Running Fisher test, a nonparametric correlation test. Using the biomarker, the authors identified conditions that led to p53 activation, including exposure to the chem. nutlin-3 which disrupts interactions between p53 and the neg. regulator MDM2 or by knockdown of MDM2. The expression of most of the genes in the biomarker (75%) were found to depend on p53 activation status based on gene behavior after TP53 overexpression or knockdown. The biomarker identified DDI chems. that were strong inducers of p53 in wild-type cells; these p53 responses were decreased or abolished in cells after p53 knockdown by siRNAs. Using the biomarker, the authors screened ∼1950 chems. in ∼9800 human cell line chem. vs. control comparisons and identified ∼100 chems. that caused p53 activation. Among the pos. chems. were many that are known to activate p53 through direct and indirect DNA damaging mechanisms. These results contribute to the evidence that the TGx-DDI biomarker is useful for identifying chems. that cause DDI and activate p53. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Application In Synthesis of 4-Benzyloxyphenol).

4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Esters are also usually derived from carboxylic acids. It may also be obtained by reaction of acid anhydride or acid halides with alcohols or by the reaction of salts of carboxylic acids with alkyl halides. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Application In Synthesis of 4-Benzyloxyphenol

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Build-Couple-Transform: A Paradigm for Lead-like Library Synthesis with Scaffold Diversity was written by Uguen, Melanie;Davison, Gemma;Sprenger, Lukas J.;Hunter, James H.;Martin, Mathew P.;Turberville, Shannon;Watt, Jessica E.;Golding, Bernard T.;Noble, Martin E. M.;Stewart, Hannah L.;Waring, Michael J.. And the article was included in Journal of Medicinal Chemistry in 2022.Application In Synthesis of 2-Methoxyethylamine The following contents are mentioned in the article:

High-throughput screening provides one of the most common ways of finding hit compounds Lead-like libraries e.g., I, in particular, provide hits with compatible functional groups and vectors for structural elaboration and phys. properties suitable for optimization. Library synthesis approaches can lead to a lack of chem. diversity because they employ parallel derivatization of common building blocks using single reaction types. This problem through a “build-couple-transform” paradigm for the generation of lead-like libraries e.g., I with scaffold diversity was addressed. Nineteen transformations of 4-oxo-2-butenamides RC(O)CH=CHC(O)N(R¹)R² (R = Ph, 4-methoxyphenyl, tetrahydro-2H-pyran-4-yl, etc.; R¹ = H; R² = 2-methoxyethyl, Bn, 1-methyl-1H-pyrazol-3-yl; R¹R² = -(CH₂)₅-, -(CH₂)₂O(CH₂)₂-) scaffold template were optimized, including 1,4-cyclizations, 3,4-cyclizations, reductions, and 1,4-additions A pool-transformation approach efficiently explored the scope of these transformations for nine different building blocks and synthesized a >170-member library with enhanced chem. space coverage and favorable drug-like properties. Screening revealed hits against CDK2. This work establishes the build-couple-transform concept for the synthesis of lead-like libraries e.g., I and provides a differentiated approach to libraries with significantly enhanced scaffold diversity. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3Application In Synthesis of 2-Methoxyethylamine).

2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Esters are widespread in nature and are widely used in industry. In nature, fats are in general triesters derived from glycerol and fatty acids. Esters are responsible for the aroma of many fruits, including apples, durians, pears, bananas, pineapples, and strawberries. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Application In Synthesis of 2-Methoxyethylamine

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Comprehensive characterization of hydrothermal liquefaction products obtained from woody biomass under various alkali catalyst concentrations was written by Hwang, Hyewon;Lee, Jae Hoon;Choi, In-Gyu;Choi, Joon Weon. And the article was included in Environmental Technology in 2019.COA of Formula: C9H12O3 The following contents are mentioned in the article:

Hydrothermal liquefaction (HTL) of lignocellulosic biomass has been widely investigated for the production of renewable and alternative bio-crude oil. In this study, catalytic hydrothermal processing of two biomasses (larch and Mongolian oak) was performed using different K₂CO₃ concentrations (0, 0.1, 0.5, 1.0 wt% of solvent) to improve fuel yield and properties. HTL oil, hydrochar, water-soluble fraction (WSF) and gas were characterized, and carbon balance was investigated. As a result, the maximum yield of HTL oil, 27.7 wt% (Mongolian oak) and 25.7 wt% (larch), and the highest carbon conversion ratio was obtained with 0.5 wt% of catalyst. The high catalyst concentration also resulted in an increase in higher heating values up to 31.9 MJ/kg. In addition, the amount of organic compounds in HTL oil also increased, specifically for lignin-derived compounds including catechol and hydroquinone which can be derived from secondary hydrolysis of lignin. On the other hand, formation of hydrochar was suppressed with the addition of alkali catalyst and the yield dramatically decreased from 30.7-40.8 weight% to 20.0-21.8 weight%. Furthermore, it was revealed that WSF had low organic carbon content less than 3.4% and high potassium content mostly derived from alkali catalyst, indicating that it may be reusable with simple purification This work suggests that the addition of the proper amount of alkali catalyst can improve the production efficiency and quality of bio-crude oil, and another potential of WSF to be recyclable in further work. This study involved multiple reactions and reactants, such as 4-Hydroxy-3-methoxyphenethanol (cas: 2380-78-1COA of Formula: C9H12O3).

4-Hydroxy-3-methoxyphenethanol (cas: 2380-78-1) belongs to ethers. Esters perform as high-grade solvents for a broad array of plastics, plasticizers, resins, and lacquers, and are one of the largest classes of synthetic lubricants on the commercial market. Esters contain a carbonyl center, which gives rise to 120° C–C–O and O–C–O angles. Unlike amides, esters are structurally flexible functional groups because rotation about the C–O–C bonds has a low barrier. Their flexibility and low polarity is manifested in their physical properties; they tend to be less rigid (lower melting point) and more volatile (lower boiling point) than the corresponding amides. COA of Formula: C9H12O3

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Design and synthesis of novel benzothiophene analogs as selective estrogen receptor covalent antagonists against breast cancer was written by Bai, Chengfeng;Ren, Shengnan;Wu, Shuangjie;Zhu, Meiqi;Luo, Guoshun;Xiang, Hua. And the article was included in European Journal of Medicinal Chemistry in 2021.Recommanded Product: 4-Benzyloxyphenol The following contents are mentioned in the article:

Endocrine therapy (ET) has benefited patients with estrogen receptor alpha (ERα) pos. breast cancer for decades. Selective estrogen receptor modulator (SERM) such as Tamoxifen represents the clin. standard of care (SoC). Despite the therapeutic importance of current SoC agents, 30-50% of prolonged treatment patients inevitably generated resistant tumor cells, usually eventually suffered tumor relapse and developed into metastatic breast cancer (MBC), which was the leading cause of female cancer-related mortality. Among these, most resistant tumors remained dependent on ERα signaling, which reignited the need for the next generation of ERα related agents. Authors hypothesized that selective estrogen receptor covalent antagonists targeting ERα would provide a therapeutic alternative. In the current work, series of novel benzothiophene hybrids I (R₁ = H, Me; R₂ = Me; R₁R₂ = (CH₂)₃, (CH₂)₅, etc.) II, III (R₃ = R₄ = H, Me) and IV bearing electrophile moieties were synthesized and biol. evaluated. The representative analog I (R₁R₂ = (CH₂)₃) exhibited potent anti-proliferative effect in MCF-7 cell lines in vitro, and further mechanism studies confirmed the necessity of covalent bonding. More importantly, I could attenuate the expression of TFF-1, GREB-1 and down-regulate the levels of cellular ERα protein. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2Recommanded Product: 4-Benzyloxyphenol).

4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Esterification is the general name for a chemical reaction in which two reactants (typically an alcohol and an acid) form an ester as the reaction product. Esters are common in organic chemistry and biological materials.Recommanded Product: 4-Benzyloxyphenol

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Design and synthesis of novel benzothiophene analogs as selective estrogen receptor covalent antagonists against breast cancer was written by Bai, Chengfeng;Ren, Shengnan;Wu, Shuangjie;Zhu, Meiqi;Luo, Guoshun;Xiang, Hua. And the article was included in European Journal of Medicinal Chemistry in 2021.COA of Formula: C13H12O2 The following contents are mentioned in the article:

Endocrine therapy (ET) has benefited patients with estrogen receptor alpha (ERα) pos. breast cancer for decades. Selective estrogen receptor modulator (SERM) such as Tamoxifen represents the clin. standard of care (SoC). Despite the therapeutic importance of current SoC agents, 30-50% of prolonged treatment patients inevitably generated resistant tumor cells, usually eventually suffered tumor relapse and developed into metastatic breast cancer (MBC), which was the leading cause of female cancer-related mortality. Among these, most resistant tumors remained dependent on ERα signaling, which reignited the need for the next generation of ERα related agents. Authors hypothesized that selective estrogen receptor covalent antagonists targeting ERα would provide a therapeutic alternative. In the current work, series of novel benzothiophene hybrids I (R₁ = H, Me; R₂ = Me; R₁R₂ = (CH₂)₃, (CH₂)₅, etc.) II, III (R₃ = R₄ = H, Me) and IV bearing electrophile moieties were synthesized and biol. evaluated. The representative analog I (R₁R₂ = (CH₂)₃) exhibited potent anti-proliferative effect in MCF-7 cell lines in vitro, and further mechanism studies confirmed the necessity of covalent bonding. More importantly, I could attenuate the expression of TFF-1, GREB-1 and down-regulate the levels of cellular ERα protein. This study involved multiple reactions and reactants, such as 4-Benzyloxyphenol (cas: 103-16-2COA of Formula: C13H12O2).

4-Benzyloxyphenol (cas: 103-16-2) belongs to ethers. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.COA of Formula: C13H12O2

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Novel Soloxolone Amides as Potent Anti-Glioblastoma Candidates: Design, Synthesis, In Silico Analysis and Biological Activities In Vitro and In Vivo was written by Markov, Andrey V.;Ilyina, Anna A.;Salomatina, Oksana V.;Sen’kova, Aleksandra V.;Okhina, Alina A.;Rogachev, Artem D.;Salakhutdinov, Nariman F.;Zenkova, Marina A.. And the article was included in Pharmaceuticals in 2022.COA of Formula: C3H9NO The following contents are mentioned in the article:

The modification of natural or semisynthetic triterpenoids with amines can be explored as a promising strategy for improving their pharmacol. properties. Here, we report the design and synthesis of 11 novel amide derivatives of soloxolone Me (SM), a cyano enone-bearing derivative of 18βH-glycyrrhetinic acid. Anal. of their bioactivities in vitro and in silico revealed their high toxicity against a panel of tumor cells (average IC50(24h) = 3.7 μM) and showed that the formation of amide moieties at the C-30 position of soloxolone did not enhance the cytotoxicity of derivatives toward tumor cells compared to SM, though it can impart an ability to pass across the blood-brain barrier. Further HPLC-MS/MS and mechanistic studies verified significant brain accumulation of hit compound 12 (soloxolone tryptamide) in a murine model and showed its high anti-glioblastoma potential. It was found that 12 induced ROS-dependent and autophagy-independent death of U87 and U118 glioblastoma cells via mitochondrial apoptosis and effectively blocked their clonogenicity, motility and capacity to form vessel-like structures. Further in vivo study demonstrated that i.p. injection of 12 at a dosage of 20 mg/kg effectively inhibited the growth of U87 glioblastoma in a mouse xenograft model, reducing the proliferative potential of the tumor and leading to a depletion of collagen content and normalization of blood vessels in tumor tissue. The obtained results clearly demonstrate that 12 can be considered as a promising leading compound for drug development in glioblastoma treatment. This study involved multiple reactions and reactants, such as 2-Methoxyethylamine (cas: 109-85-3COA of Formula: C3H9NO).

2-Methoxyethylamine (cas: 109-85-3) belongs to ethers. Carboxylic acid esters of low molecular weight are colourless, volatile liquids with pleasant odours, slightly soluble in water. Cyclic esters are called lactones, regardless of whether they are derived from an organic or inorganic acid. One example of an organic lactone is γ-valerolactone.COA of Formula: C3H9NO

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem

Hydrotropic Extraction of Carnosic Acid from Rosemary with Short-Chain Alkyl Polyethylene Glycol Ethers was written by Mazaud, Agathe;Lebeuf, Raphael;Laguerre, Mickael;Nardello-Rataj, Veronique. And the article was included in ACS Sustainable Chemistry & Engineering in 2020.Application of 112-59-4 The following contents are mentioned in the article:

Carnosic acid (CA) is a hydrophobic secondary metabolite and the main antioxidant of rosemary. Extractions of CA from whole leaves of rosemary have been performed with aqueous solutions of 12 short-chain alkyl polyethylene glycol ethers, abbreviated as C_iE_j with i = 4-8 and j = 1-4. Such compounds act as hydrotropes which are known to enhance the solubilization of hydrophobic mols. in water while avoiding the formation of liquid crystals like surfactants. The extractions are compared with those carried out with alcs., sodium xylene sulfonate (SXS) which is an archetypical ionic hydrotrope, and longer C_iE_j (i = 10 or 12 and j = 4) which behave as true surfactants. C₅E₂ and C₄E₁ are the best candidates and provide 1.21 g/L CA in 21 h and 1.02 g/L in 8 h, resp. They are more efficient than SXS and alc. aqueous solutions Correlations between the chem. structure and activity have highlighted three requirements for better performances: (i) a small mol. volume V_m (<250 ų), (ii) a log P above 1, and (iii) a linear alkyl chain rather than a branched one. Finally, kinetic study and optical microscopy observations of the leaves after extraction give insight into the mode of action of the C₄E_j compared to ethanol. Here, we investigate the use of aqueous solutions of nonionic hydrotropes to extract phytochems. in a process that mitigates emissions of volatile organic compounds compared to extraction routes using conventional solvents. This study involved multiple reactions and reactants, such as 2-(2-(Hexyloxy)ethoxy)ethanol (cas: 112-59-4Application of 112-59-4).

2-(2-(Hexyloxy)ethoxy)ethanol (cas: 112-59-4) belongs to ethers. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Liquid esters of low volatility serve as softening agents for resins and plastics. Esters also include many industrially important polymers. Polymethyl methacrylate is a glass substitute sold under the names Lucite and Plexiglas; polyethylene terephthalate is used as a film (Mylar) and as textile fibres sold as Terylene, Fortrel, and Dacron.Application of 112-59-4

Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem