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Ethyl carbonate

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PubCompare.ai's powerful AI-driven platform can help optimize your research protocols and enhance reproducibility when working with Ethyl carbonate. The tool can help you screen protocol literature more efficiently, and leverage AI to pinpoint critical insights. This allows you to identify the most effective protocols related to Ethyl carbonate for your specific research goals. The platform's AI-driven analysis can highlight key differences in protocol effectiveness, enabling you to choose the best option for reproducibility and accuracy.

Q: What are some common applications of Ethyl carbonate?

Ethyl carbonate is used in a variety of applications, including as a solvent, an intermediate in organic synthesis, and a co-solvent in some cosmetic and personal care products. It is also used in the production of certain plastics and as a fuel additive. Due to its relatively low toxicity and eco-friendly nature, Ethyl carbonate is considered a versatile and useful chemical compound.

Q: Are there any safety considerations when working with Ethyl carbonate?

While Ethyl carbonate is generally considered a safe and eco-friendly chemical, there are still some safety considerations to keep in mind. It is a flammable liquid, so proper precautions should be taken to avoid ignition sources. Additionally, Ethyl carbonate should be handled in a well-ventilated area, as the vapors can be irritating to the eyes and respiratory system. As with any chemical, it's important to follow all applicable safety protocols and wear appropriate personal protective equipment when working with Ethyl carbonate.

Q: How can I find the best protocols and procedures for using Ethyl carbonate in my research?

PubCompare.ai's AI-driven platform can help you identify the most effective protocols and procedures for using Ethyl carbonate in your research. The tool can scree protocol literature more efficiently, and use AI to pinpoit critical insights that help you choose the best option for reproducibility and accuracy. By leveraging PubCompare.ai, you can save time, enhance the quality of your research, and improve your overall outcomes when working with Ethyl carbonate.

Ethyl carbonate, also known as ethyl ester of carbonic acid, is a colorless, flammable liquid with a mild odor.
It is used as a solvent, an intermediate in organic synthesis, and a co-solvent in some cosmetic and personal care products.
Ethyl carbonate can be formed through the reaction of ethanol and carbon dioxide.
It is considered a relatively safe and eco-friendly chemical, with low toxicity and biodegradability.
Researchers can leverage PubCompare.ai's powerful AI-driven platform to optimize their research protocols and enhance reproducibility when working with ethyl carbonate, as the tool can help locate the best protocols from literature, preprints, and patents, as well as identify the most effective products and procedures for their experiments.

Most cited protocols related to «Ethyl carbonate»

Antibacterial NACP Nanocomposite Development

Cited 9 times

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Publication 2013

2-propylamine A-A-1 antibiotic Acetic Acid Anti-Bacterial Agents barium glass filler Biofilms bisphenol A camphorquinone Carbonate, Calcium Dental Health Services Dentsply dicalcium phosphate Electrostatics Esters Fungus, Filamentous gamma-methacryloxypropyltrimethoxysilane Ions Light Methacrylate Molar Paste Renamel Resins, Plant SNCA protein, human Triad resin triethylene glycoldimethacrylate

Preparation and Characterization of Lipid-based Nanoparticles

Cited 8 times

Stearic acid and SPAN 80 were purchased from Merck (Merck KGaA, Darmstadt, Germany). Arachidic acid, Tween 60, Tween 80, poly(vinyl alcohol), L-lysine monohydrochloride, lithium carbonate, dansyl chloride, methylamine hydrochloride, triethylamine and sodium acetate were purchased from Sigma-Aldrich (St. Louis, MO, USA) and Miglyol 812 was purchased from Caelo (Caesar & Loretz GmbH, Hilden, Germany). Precirol ATO 5 and Compritol 888 ATO were kindly provided by Gattefossé (Saint Priest Cedex, France). L-Phenylalanine ethyl-ester hydrochloride was purchased from Fluka (Fluka Chemie GmbH, Buchs, Switzerland), acetic acid was obtained from VWR Chemicals (VWR International S.A.S., Fontenay-sous-Bois, France) and acetonitrile and methanol were obtained from Honeywell (Honeywell Riedel-de Häen AG, Seelze, Germany). Aqueous solutions were prepared with double-deionized water (Arium Pro, Sartorius AG, Göttingen, Germany).

Albuquerque J., Casal S., Páscoa R.N., Van Dorpe I., Fonseca A.J., Cabrita A.R., Neves A.R, & Reis S. (2020). Applying nanotechnology to increase the rumen protection of amino acids in dairy cows. Scientific Reports, 10, 6830.

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Publication 2020

Acetic Acid acetonitrile arachidic acid Cedax Compritol ATO 888 dansyl chloride L-phenylalanine ethylester Lithium Carbonate Lysine Methanol methylamine hydrochloride miglyol 812 Polyvinyl Alcohol precirol ATO 5 Sodium Acetate Span 80 stearic acid triethylamine Tween 60 Tween 80

Synthesis and Evaluation of Glycyrrhetinic Acid Derivatives

Cited 8 times

Reagents: CDDO-Me 1 was synthesized from oleanolic acid according to a previously described method[5 (link)] with 10 % yield (NMR ¹H and ¹³C data).
18βH-Glycyrrhetinic acid acetate 2, obtained from a licorice extract, was used as starting material (purity∼94 %).[39 ]
General experimental procedures: Melting points were determined on a Hoover melting point apparatus and were uncorrected. The elemental composition of the products was determined from high-resolution mass spectra recorded on a DFS (Double Focusing Sector) Thermo Electron Corporation instrument. ¹H and ¹³C NMR spectra were measured from CDCl₃ solutions on Bruker spectrometers: AM-400 (400.13mhz for ¹H, 100.61mhz for ¹³C) and DRX-500 (500.13mhz for ¹H, 125.76mhz for ¹³C). Chloroform was used as the internal standard (δ_H 7.24 ppm, δ_C 76.90 ppm). The structure of the compounds was determined by NMR from proton spin–spin coupling constants in ¹H,¹H double-resonance spectra, and by analyzing ¹³C NMR proton-selective and off-resonance saturation spectra, 2D ¹³C,¹H correlated spectroscopy on CH constants (COSY, ¹J_C,H=135 Hz; and COLOC, ^{2, 3}J_C,H=10 Hz, correspondingly), and 1D ¹³C,¹H long-range J modulation difference (LRJMD, J_C,H=10 Hz). Flash column chromatography was performed with silica gel (Merck, 60–200 mesh) and neutral alumina (Chemapol, 40–250 mesh).
Methyl 18βH-Glycyrrhetinate acetate (3):[42 ] A solution of diazomethane in ether was added dropwise at 0°C to a stirred suspension of 2 (10 g, 19.0 mmol) in methanol (200 mL) until the originally colorless mixture turned yellow. The resulting mixture was allowed to stand at room temperature overnight. The solvent was removed and the product was purified by crystallization (chloroform/methanol; yield=9.1 g, 89 %). M.p. 303–304°C; ¹H NMR (CDCl₃): δ=0.76 (dd, ³J(H^5a,H^6a)=12.5, ³J(H^5a,H^6e)=1.5 Hz; H^5a), 0.76 (s, 3 H; C28-H₃), 0.84 (s, 6 H; C23-H₃, C24-H₃), 0.97 (dm, ²J(H^16e,H^16a)=13.8 Hz; H^16e), 1.01 (ddd, ²J(H^1a,H^1e)=13.5, ³J(H^1a,H^2a)=13.5, ³J(H^1a,H^2e)=3.7 Hz; H^1a), 1.08 (s, 3 H; C26-H₃), 1.10 (s, 3 H; C29-H₃), 1.12 (s, 3 H; C25-H₃), 1.14 (dm, ²J(H^15e_,H^15a)=13.8 Hz; H^15e), 1.23–1.39 (m, 4 H; H⁷, H^21a, 2 H²²), 1.32 (s, 3 H; C27-H₃), 1.41 (dddd, ²J(H^6a_,H^6e)=13.5, ³J(H^6a_,H^7a)=13.5, ³J(H^6a_,H^5a)=12.0, ³J(H^6a,H^7e)=3.2 Hz; H^6a), 1.51–1.66 (m, 3 H; H^6e, H^2e, H^7′), 1.57 (dd, ²J(H^19a,H^19e)=13.5, ³J(H^19a,H^18a)=13.5 Hz; H^19a), 1.66 (dddd, ²J(H^2a,H^2e)=13.5, ³J(H^2a,H^1a)=13.5, ³J(H^2a,H^3a)=11.7, ³J(H^2a,H^1e)=3.7 Hz; H^2a), 1.78 (ddd, ²J(H^15a,H^15e)=13.8, ³J(H^15a,H^16a)=13.8, ³J(H^15a_,H^16e)=4.5 Hz; H^15a), 1.88 (ddd, ²J(H^19e,H^19a)=13.5, ³J(H^19e,H^18a)=4.2, ⁴J(H^19e,H^21e)=2.7 Hz; H^19e), 1.95 (dm ²J(H^21e,H^21a)=10 Hz; H^21e), 1.98 (ddd, ²J(H^16a,H^16e)=13.8, ³J(H^16a,H^15a)=13.8, ³J(H^16a,H^15e)=4.8 Hz; H^16a), 2.00 (s, 3 H; C33-H₃), 2.04 (dd, ³J(H^18a,H^19a)=13.5, ³J(H^18a,H^19e)=4.2 Hz; H^18a), 2.32 (s, 1 H; H^9a), 2.76 (ddd ²J(H^1e,H^1a)=13.5, ³J(H^1e,H^2a)=3.7, ³J(H^1e,H^2e)=3.0 Hz; H^1e), 3.64 (s, 3 H; OC31-H₃), 4.47 (dd, ³J(H^3a,H^2a)=11.7, ³J(H^3a,H^2e)=4.7 Hz; H^3a), 5.62 (s, 1 H; H¹²); ¹³C NMR (CDCl₃): δ=38.63 (t, C1), 23.41 (t, C2), 80.45 (d, C3), 37.88 (s, C4), 54.88 (d, C5), 17.22 (t, C6), 32.55 (t, C7), 43.03 (s, C8), 61.56 (d, C9), 36.78 (s, C10), 199.85 (s, C11), 128.34 (d, C12), 169.01 (s, C13), 45.23 (s, C14), 26.31 (t, C15), 26.26 (t, C16), 31.67 (s, C17), 48.25 (d, C18), 40.93 (t, C19), 43.87 (s, C20), 30.98 (t, C21), 37.59 (t, C22), 27.89 (q, C23), 16.52 (q, C24), 16.24 (q, C25), 18.52 (q, C26), 23.17 (q, C27), 28.36 (q, C28), 28.15 (q, C29), 176.73 (s, C30), 51.58 (q, C31), 170.77 (s, C32), 21.13 (q, C33); HRMS: m/z calcd for C₃₃H₅₀O₅: 526.7471; found: 526.3658.
Methyl 3 β-Acetoxy-18 βH-olean-12-en-30-oate (4):[43 ] A solution of conc. hydrochloric acid (50 mL) was added dropwise at 10°C to a stirred suspension of 3 (9.1 g, 17.3 mmol) and zinc powder (18.2 g, 280 mmol) in dioxane (300 mL) over 2 h. The reaction mixture was stirred for a further 3 h at 5–10°C, concentrated in a vacuum, diluted with water (1 L), and filtered. The solid was dried and subjected to flash column chromatography (silica gel; benzene followed by chloroform) to give crude 4 (yield=6.8 g, 77 %). This material was used for the next reaction without further purification. An analytically pure sample was obtained by recrystallization from a mixture chloroform/methanol. M.p. 265–267°C; ¹H NMR (CDCl₃): δ=0.74 (s, 3 H; C28-H₃), 0.81 (dd, ³J(H^5a,H^6a)=12.0, ³J(H^5a,H^6e)=1.6 Hz; H^5a), 0.82–0.86 (m, H^16e), 0.83 (s, 3 H; C24-H₃), 0.84 (s, 3 H; C23-H₃), 0.93 (s, 6 H; C25-H₃, C26-H₃), 0.94 (dm ²J(H^15e,H^15a)=13.5 Hz; H^15e), 1.02 (m; H¹), 1.09 (s, 3 H; C29-H₃), 1.10 (s, 3 H; C27-H₃), 1.17–1.35 (m, 4 H; H⁷, H²¹, 2 H²²), 1.39 (m, H^6a), 1.44–1.64 (m, 7 H; H^1′, 2 H², H^6e, H^7′, H^9a, H¹⁹), 1.73 (ddd, ²J(H^15a,H^15e)=13.5, ³J(H^15a,H^16a)=13.5, ³J(H^15a,H^16e) 4.6 Hz; H^15a), 1.79–1.93 (m, 5 H; 2 H¹¹, H¹⁸, H^19′, H^21′), 1.92 (m; H^16a), 2.01 (s, 3 H; C33-H₃), 3.64 (s, 3 H; OC31-H₃), 4.47 (dd, ³J(H^3a,H^2a)=10.0, ³J(H^3a,H^2e)=6.0 Hz; H^3a), 5.23 (t, ²J(H¹²,H¹¹)=3.6 Hz; H¹²); ¹³C NMR (CDCl₃): δ=38.13 (t, C1), 23.42 (t, C2), 80.74 (d, C3), 37.56 (s, C4), 55.13 (d, C5), 18.11 (t, C6), 32.46 (t, C7), 39.65 (s, C8), 47.42 (d, C9), 36.70 (s, C10), 23.34 (t, C11), 122.34 (d, C12), 144.23 (s, C13), 41.38 (s, C14), 25.99 (t; C15), 26.82 (t, C16), 31.79 (s, C17), 48.05 (d, C18), 42.68 (t, C19), 44.12 (s, C20), 31.15 (t, C21), 38.25 (t, C22), 27.89 (q, C23), 16.54 (q, C24), 15.41 (q, C25), 16.64 (q, C26), 25.77 (q, C27), 28.03 (q, C28), 28.38 (q, C29), 177.46 (s, C30), 51.35 (q, C31), 170.77 (s, C32), 21.13 (q, C33); HRMS: m/z calcd for C₃₃H₅₂O₄: 512.7636; found: 512.3866.
Methyl 3β-acetoxy-12-oxo-18βH-olean-30-oate (5): A mixture of hydrogen peroxide (∼30 %, 25 mL) and acetic acid (25 mL) was added dropwise at 80°C to a stirred suspension of 4 (3.0 g, 5.7 mmol) in acetic acid (100 mL) over 1 h. The reaction mixture was stirred for a further 30 min at 80°C, cooled to room temperature, and diluted with water (500 mL). The solid was filtered, washed with water, and dried to give crude 5 (yield=6.8 g, 96 %). This material was used for the next reaction without further purification. An analytically pure sample was obtained by recrystallization from a mixture chloroform/methanol. M.p. 296–299°C; ¹H NMR (CDCl₃): δ=0.79–0.88 (m, 2 H; H^5a, H^16e), 0.82 (s, 3 H; C28-H₃), 0.83 (s, 3 H; C24-H₃), 0.84 (s, 3 H; C23-H₃), 0.86 (s, 3 H; C25-H₃), 0.90 (s, 3 H; C27-H₃), 0.92–1.01 (m, 2 H; H¹, H^15e), 1.09 (s, 3 H; C29-H₃), 1.10 (s, 3 H; C26-H₃), 1.19 (dd, ²J(H^19a,H^19e)=13.4, ³J(H^19a,H¹⁸)=13.4 Hz; H^19a), 1.18–1.27 (m, 2 H; H^21a, H^22e), 1.31–1.48 (m, 4 H; 2 H⁷, H^22a, H⁶), 1.49–1.64 (m, 4 H; H^1′, 2 H², H^6′), 1.64 (dd ³J(H^9a,H^11a)=13.0, ³J(H^9a,H^11e)=5.1 Hz; H^9a), 1.74 (m, H¹⁸), 1.76 (m, H^15a), 1.85 (ddd, ²J(H^16a,H^16e)=13.2, ³J(H^16a,H^15a)=13.2, ³J(H^16a,H^15e)=4.2 Hz; H^16a), 1.91 (dm, ²J(H^21e,H^21a)=13.2 Hz; H^21e), 2.00 (s, 3 H; C33-H₃), 2.12 (dd, ²J(H^11a,H^11e)=17.0, ³J(H^11a,H^9a)=13.0 Hz; H^11a), 2.23 (dd, ²J(H^11e,H^11a)=17.0, ³J(H^11e,H^9a)=5.1 Hz; H^11e), 2.54 (ddd, ²J(H^19e,H^19a)=13.4, ³J(H^19e,H¹⁸)=3.4, ⁴J(H^19e,H^21e)=2.8 Hz; H^19e), 2.72 (d, ³J(H¹³,H¹⁸)=4.4 Hz; H¹³), 3.68 (s, 3 H; OC31-H₃), 4.44 (dd, ³J(H^3a,H^2a)=11.4, ³J(H^3a,H^2e)=4.8 Hz; H^3a); ¹³C NMR (CDCl₃): δ=37.50 (t, C1), 23.26 (t, C2), 80.28 (d, C3), 37.60 (s, C4), 55.04 (d, C5), 18.05 (t, C6), 31.63 (t, C7), 41.41 (s, C8), 49.32 (d, C9), 36.67 (s, C10), 38.28 (t, C11), 211.91 (s, C12), 50.08 (d, C13), 41.90 (s, C14), 25.84 (t, C15), 26.29 (t, C16), 32.01 (s, C17), 38.41 (d, C18), 34.05 (t, C19), 43.97 (s, C20), 31.19 (t, C21), 38.33 (t, C22), 27.75 (q, C23), 16.30 (q, C24), 15.16 (q, C25), 15.95 (q, C26), 20.78 (q, C27), 26.83 (q, C28), 28.59 (q, C29), 177.44 (s, C30), 51.36 (q, C31), 170.70 (s, C32), 21.09 (q, C33); HRMS: m/z calcd for C₃₃H₅₂O₅: 528.7630; found: 528.3815.
Methyl 3β-acetoxy-12-oxo-18βH-olean-9(11)-en-30-oate (6): Compound 6 was synthesized according to a known method.[44 ] Briefly, a solution of bromine (0.5 mL, 9.8 mmol) in glacial acetic acid (50 mL) was added dropwise at 80°C to a stirred solution of 5 (4.0 g, 7.6 mmol) in glacial acetic acid (150 mL) over 1 h. The reaction mixture was stirred for a further 1 hour at 80°C, cooled to room temperature, diluted with water (1.5 L) and filtered. The solid was washed with water, dried, and subjected to flash column chromatography (silica gel, chloroform) to give a solid 6 (yield=3.0 g, 75 %). This material was used for the next reaction without further purification. An analytically pure sample was obtained by recrystallization from a mixture chloroform/methanol. M.p. 298°C; ¹H NMR (CDCl₃): δ=0.84 (m; H^16e), 0.85 (s, 3 H; C24-H₃), 0.86 (s, 6 H; C23-H₃, C28-H₃), 0.91 (s, 3 H; C27-H₃), 0.94 (dm, ³J(H^5a,H^6a)=10 Hz; H^5a), 1.01 (dm, ²J(H^15e,H^15a)=13.2 Hz; H^15e), 1.07 (s, 3 H; C29-H₃), 1.16 (s, 3 H; C25-H₃), 1.20 (dd, ²J(H^19a,H^19e)=13.3, ³J(H^19a,H¹⁸)=13.3 Hz; H^19a), 1.16–1.27 (m, 2 H; H^21a, H^22e), 1.32 (s, 3 H; C26-H₃), 1.35–1.44 (m, 2 H; H^1a, H^7e), 1.46 (ddd, ²J(H^22a,H^22e)=14.0, ³J(H^22a,H^21a)=14.0, ³J(H^22a,H^21e)=4.2 Hz; H^22a), 1.55–1.73 (m, 5 H; 2 H⁶, H^7a, 2 H²), 1.77 (m; H^15a), 1.83 (m; H^16a), 1.90 (m, 2 H; H^1e, H^21e), 1.93 (dm, ³J(H¹⁸,H^19a)=13.3; H¹⁸), 2.00 (s, 3 H; C33-H₃), 2.16 (ddd, ²J(H^19e,H^19a)=13.3, ³J(H^19e,H¹⁸)=3.4, ⁴J(H^19e,H^21e)=2.8 Hz; H^19e), 2.92 (d, ³J(H¹³,H¹⁸)=4.7 Hz; H¹³), 3.69 (s, 3 H; OC31-H₃), 4.43 (dd, ³J(H^3a,H^2a)=11.7, ³J(H^3a,H^2e)=4.5 Hz; H^3a), 5.72 (s; H¹¹); ¹³C NMR (CDCl₃): δ=35.86 (t, C1), 23.66 (t, C2), 79.49 (d, C3), 37.95 (s, C4), 50.08 (d, C5), 17.67 (t, C6), 32.66 (t, C7), 45.29 (s, C8), 177.61 (s, C9), 39.59 (s, C10), 122.89 (d, C11), 201.14 (s, C12), 47.70 (d, C13), 41.61 (s, C14), 26.03 (t, C15), 26.03 (t, C16), 31.87 (t, C17), 37.81 (d, C18), 33.69 (t, C19), 43.88 (s, C20), 31.10 (t, C21), 38.13 (t, C22), 27.77 (q, C23), 16.46 (q, C24), 23.79 (q, C25), 23.85 (q, C26), 21.84 (q, C27), 26.90 (q, C28), 28.45 (q, C29), 177.22 (s, C30), 51.32 (q, C31), 170.59 (s, C32), 21.01 (q, C33); HRMS: m/z calcd for C₃₃H₅₀O₅: 526.7471; found: 526.3658.
Methyl 3β-hydroxy-12-oxo-18βH-olean-9(11)-en-30-oate (7): A mixture of 6 (6.2 g, 11.8 mmol) and KOH (41 g, 732 mmol) in methanol (400 mL) was heated under reflux for 1.5 h. The resulting solution was cooled to room temperature, concentrated in vacuo, and 10 % aqueous hydrochloric acid solution was added. The mixture was extracted with chloroform/ethyl acetate (1:4, 3×75 mL). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (3×50 mL) and brine (3×50 mL), and dried over magnesium sulfate. The solvent was removed to give a solid 7 (yield=5.13 g, 90 %). This material was used for the next reaction without further purification. An analytically pure sample was obtained by recrystallization from a mixture chloroform/methanol. M.p. 202–203°C; ¹H NMR: δ=0.80 (s, 3 H; C24-H₃), 0.89 (s, 3 H; C28-H₃), 0.94 (s, 3 H; C27-H₃), 1.01 (s, 3 H; C23-H₃), 1.08 (s, 3 H; C29-H₃), 1.16 (s, 3 H; C25-H₃), 1.35 (s, 3 H; C26-H₃), 0.83–0.91 (m, 2 H; H^5a, H^16e), 1.04 (dm, ²J(H^15e,H^15a)=12.8 Hz; H^15e), 1.23 (dd, ²J(H^19a,H^19e)=13.2, ³J(H^19a,H¹⁸)=13.2 Hz; H^19a), 1.18–1.25 (m; H^21a), 1.27 (dm, ²J(H^22e,H^22a)=14.0 Hz; H^22e), 1.31 (m; H^1a), 1.44 (dm, ²J(H^7e,H^7a)=9.8 Hz; H^7e), 1.49 (ddd, ²J(H^22a,H^22e)=14.0, ³J(H^22a,H^21a)=14.0, ³J(H^22a,H^21e)=4.2 Hz; H^22a), 1.55–1.76 (m, 5 H; 2 H⁶, H^7a, 2 H²), 1.80 (m, H^15a), 1.85 (m; H^16a), 1.89–2.00 (m, 3 H; H^1e, H^21e, H¹⁸), 2.19 (ddd, ²J(H19^e,19^a)=13.2, ³J(H^19e,H¹⁸)=3.2, ⁴J(H^19e,H^21e)=2.7 Hz; H^19e), 2.95 (d, ³J(H¹³,H¹⁸) 4.7 Hz; H¹³), 3.18 (dd ³J(H^3a,H^2a)=11.7, ³J(H^3a,H^2e)=4.4 Hz; H^3a), 3.71 (s, 3 H; OC31-H₃), 5.76 (s, H¹¹); ¹³C NMR (CDCl₃): δ=36.22 (t, C1), 27.38 (t, C2), 77.83 (d, C3), 39.11 (s, C4), 50.06 (d, C5), 17.87 (t, C6), 32.79 (t, C7), 45.39 (s, C8), 178.10 (s, C9), 39.81 (s, C10), 122.85 (d, C11), 201.36 (s, C12), 47.76 (d, C13), 41.70 (s, C14), 26.14 (t, C15), 26.12 (t, C16), 31.95 (s, C17), 37.88 (d, C18), 33.79 (t, C19), 43.95 (s, C20), 31.17 (t, C21), 38.21 (t, C22), 27.96 (q, C23), 15.44 (q, C24), 23.81 (q, C25), 23.87 (q, C26), 21.99 (q, C27), 26.96 (q, C28), 28.52 (q, C29), 177.33 (s, C30), 51.43 (q, C31); HRMS: m/z calcd for C₃₁H₄₈O₄: 484.7104; found: 484.3553.
Methyl 3,12-Dioxo-18βH-olean-9(11)-en-30-oate (8): Jones reagent (5 mL), prepared from Na₂Cr₂O₇⋅2 H₂O in dilute sulfuric acid (33 %)[45 ] was added dropwise to a solution of 7 (5.13 g) in acetone (500 mL) at 0°C over 30 min till the brown color persisted. The mixture was stirred for further 2.5 h at room temperature, and ethanol (10 mL) was added. The resulting mixture was concentrated in a vacuum (∼100 mL), and water (1 L) was added. The solid was filtered and dried. The ketone 8 was purified by column chromatography (neutral alumina, chloroform) (yield=4.7 g, 94 %). This material was used for the next reaction without further purification. An analytically pure sample was obtained by recrystallization from a mixture chloroform/methanol. M.p. 189–192°C; ¹H NMR (CDCl₃): δ=0.88 (s, 3 H; C28-H₃), 0.94 (s, 3 H; C27-H₃), 1.05 (s, 3 H; C24-H₃), 1.07 (s, 3 H; C29-H₃), 1.08 (s, 3 H; C23-H₃), 1.27 (s, 3 H; C25-H₃), 1.38 (s, 3 H; C26-H₃), 0.89 (m, H^16e), 1.06 (m, H^15e), 1.21 (dd, ²J(H^19a,H^19e)=13.3, ³J(H^19a,H¹⁸)=13.3 Hz; H^19a), 1.17–1.29 (m, 2 H; H^21a, H^22e), 1.43–1.50 (m, 2 H; H^5a, H⁷), 1.48 (ddd, ²J(H^22a,H^22e)=14.0, ³J(H^22a,H^21a)=14.0, ³J(H^22a,H^21e)=4.3 Hz; H^22a), 1.60–1.72 (m, 3 H; 2 H⁶, H^7′), 1.75 (m, H^1a), 1.80 (m; H^15a), 1.85 (m, H^16a), 1.92 (m, H^21e), 1.96 (ddd, ³J(H¹⁸,H^19a)=13.3, ³J(H¹⁸,H¹³)=4.7, ³J(H¹⁸,H^19e)=3.2 Hz; H¹⁸), 2.16 (m, H^1e), 2.17 (ddd, ²J(H^19e,H^19a)=13.3, ³J(H^19e,H¹⁸)=3.2, ⁴J(H^19e,H^21e)=2.8 Hz; H^19e), 2.44 (ddd, ²J(H^2e,H^2a)=15.8, ³J(H^2e,H^1a)=7.2, ³J(H^2e,H^1e)=3.8 Hz; H^2e), 2.60 (ddd, ²J(H^2a,H^2e)=15.8, ³J(H^2a,H^1a)=11.5, ³J(H^2a,H^1e)=7.3 Hz; H^2a), 2.98 (d, ³J(H¹³,H¹⁸)=4.7 Hz; H¹³), 3.70 (s, OC31-H₃), 5.78 C(H¹¹); ¹³C NMR (CDCl₃): δ=36.80 (t, C1), 33.97 (t, C2), 215.57 (s, C3), 47.35 (s, C4), 50.73 (d, C5), 18.97 (t, C6), 31.90 (t, C7), 45.46 (s, C8), 176.36 (s, C9), 39.23 (s, C10), 124.10 (d, C11), 200.78 (s, C12), 47.86 (d, C13), 41.78 (s, C14), 26.13 (t, C15), 26.11 (t, C16), 31.90 (s, C17), 37.82 (d, C18), 33.76 (t, C19), 43.90 (s, C20), 31.12 (t, C21), 38.14 (t, C22), 26.10 (q, C23), 21.25 (q, C24), 23.69 (q, C25), 23.75 (q, C26), 21.81 (q, C27), 26.94 (q, C28), 28.45 (q, C29), 177.19 (s, C30), 51.37 (q, C31); HRMS: m/z calcd for C₃₁H₄₆O₄: 484.6945; found: 484.3396.
Methyl 2-hydroxymethylene-3,12-dioxo-18βH-olean-9(11)-en-30-oate (9): Ethyl formate (3.75 mL, 39.5 mmol) and sodium methylate (2.1 g, 38.9 mmol) were added to a solution of ketone 8 (4.5 g, 9.3 mmol) in dry benzene (50 mL). The mixture was stirred at room temperature for 2 h. The reaction mixture was diluted with a mixture of chloroform/diethyl ether (1:3, 100 mL), and 5 % HCl was added to achieve pH<7. The organic layer was separated, and the aqueous layer was extracted with chloroform/diethyl ether (1:3, 3×50 mL). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (3×50 mL), and brine (3×50 mL), and dried over magnesium sulfate. The solvent was removed to give an amorphous solid 9 (yield=4.5 g, 95 %). This material was used for the next reaction without further purification. An analytically pure sample was obtained by flash column chromatography (silica gel; hexane/ethyl acetate (9:1) followed by hexane/ethyl acetate (3:1)). ¹H NMR (CDCl₃): δ=0.90 (s, 3 H; C28-H₃), 0.96 (s, 3 H; C27-H₃), 1.09 (s, 3 H; C29-H₃), 1.13 (s, 3 H; C24-H₃), 1.15 (s, 3 H; C25-H₃), 1.20 (s, 3 H; C23-H₃), 1.38 (s, 3 H; C26-H₃), 0.91 (m, H^16e), 1.07 (m, H^15e), 1.23 (dd, ²J(H^19a,H^19e)=13.3, ³J(H^19a,H¹⁸)=13.3 Hz; H^19a), 1.18–1.31 (m, 3 H; H^21a, H^22e, H^5a), 1.49 (ddd, ²J(H^22a,H^22e)=14.0, ³J(H^22a,H^21a)=14.0, ³J(H^22a,H^21e)=4.1 Hz; H^22a), 1.47–1.53 (m, H⁷), 1.59–1.67 (m, 3 H; 2 H⁶, H^7′), 1.82 (m, H^15a), 1.86 (m, H^16a), 1.94 (dddd ²J(H^21e,H^21a)=13.3, ³J(H^21e,H^22a)=4.1, ³J(H^21e,H^22e)=3.4, ⁴J(H^21e,H^19e)=2.7 Hz; H^21e), 1.99 (ddd, ³J(H¹⁸,H^19a)=13.3, ³J(H¹⁸,H¹³)=4.6, ³J(H¹⁸,H^19e)=3.3 Hz; H¹⁸), 2.21 (ddd, ²J(H^19e,H^19a)=13.3, ³J(H^19e,H¹⁸)=3.3, ⁴J(H^19e,H^21e)=2.7 Hz; H^19e), 2.26 (d, ²J(H¹,H^1′)=14.5 Hz; H¹) and 2.58 (d, ²J(H^1′,H¹)=14.5 Hz; H^1′)—AB-system, 3.02 (d, ³J(H¹³,H¹⁸)=4.6 Hz; H¹³), 3.71 (s, 3 H; OC31-H₃), 5.90 (s, H¹¹), 8.70 (d, ³J(H³²_,OH)=2.4 Hz; H³²), 14.81 (d, ³J (OH,H³²)=2.4 Hz; OH); ¹³C NMR (CDCl₃): δ=36.85 (t, C1), 104.80 (s, C2), 188.08 (s, C3), 40.32 (s, C4), 48.07 (d, C5), 18.80 (t, C6), 31.25 (t, C7), 45.55 (s, C8), 175.36 (s, C9), 38.89 (s, C10), 124.37 (d, C11), 200.73 (s, C12), 47.86 (d, C13), 41.80 (s, C14), 26.22 (t, C15), 26.14 (t, C16), 31.93 (s, C17), 37.82 (d, C18), 33.74 (t, C19), 43.93 (s, C20), 31.14 (t, C21), 38.18 (t, C22), 28.14 (q, C23), 20.65 (q, C24), 23.36 (q, C25), 23.23 (q, C26), 21.82 (q, C27), 26.96 (q, C28), 28.48 (q, C29), 177.22 (s, C30), 51.42 (q, C31), 189.65 (d, C32); HRMS: m/z calcd for C₃₂H₄₆O₅: 510.7046; found: 510.3345.
Methyl 12-oxoisoxazolo[4,5-b]-18βH-olean-9(11)-en-30-oate (10): Hydroxylamine hydrochloride (6.0 g, 86.0 mmol) was added to a solution of 9 (4.4 g, 8.6 mmol) in ethanol (120 mL) and water (12 mL). The mixture was heated under reflux for 2 h, cooled to room temperature, concentrated in vacuo, and water (100 mL) was added. The mixture was extracted with ethyl acetate (3×70 mL). The combined organic layers were washed with water (3×50 mL), brine (3×50 mL) and dried over magnesium sulfate. The solvent was evaporated and the solid was purified by column chromatography (silica gel; hexane/ethyl acetate (3:1)) to give 10 (yield=3.2 g, 73 %). ¹H NMR (CDCl₃): δ=0.91 (s, 3 H; C28-H₃), 0.98 (s, 3 H; C27-H₃), 1.10 (s, 3 H; C29-H₃), 1.15 (s, 3 H; C25-H₃), 1.24 (s, 3 H; C24-H₃), 1.32 (s, 3 H; C23-H₃), 1.40 (s, 3 H; C26-H₃), 0.91 (m, H^16e), 1.06–1.11 (m, H^15e), 1.24 (dd, ²J(H^19a,H^19e)=13.2, ³J(H^19a,H¹⁸)=13.2 Hz; H^19a), 1.19–1.34 (m, 2 H; H^21a, H^22e), 1.44–1.57 (m, 3 H; H^5a, H^22a, H⁷), 1.64–1.79 (m, 3 H; 2 H⁶, H^7′), 1.84 (m, H^15a), 1.88 (m, H^16a), 1.95 (dddd, ²J(H^21e,H^21a)=13.3, ³J(H^21e,H^22a)=4.2, ³J(H^21e,H^22e)=3.2, ⁴J(H^21e,H^19e)=2.7 Hz; H^21e), 2.00 (ddd ³J(H¹⁸,H^19a)=13.2, ³J(H¹⁸,H¹³)=4.6, ³J(H¹⁸,H^19e)=3.2 Hz; H¹⁸), 2.21 (ddd, ²J(H^19e,H^19a)=13.2, ³J(H^19e,H¹⁸)=3.2, ⁴J(H^19e,H^21e)=2.7 Hz; H^19e), 2.38 (d, ²J(H¹,H^1′)=15.0 Hz; H¹) and 2.75 (d, ²J(H^1′,H¹)=15.0 Hz; H^1′)—AB system, 3.04 (d, ³J(H¹³,H¹⁸)=4.6 Hz; H¹³), 3.73 (s, 3 H; OC31-H₃), 5.89 (s, H¹¹), 8.04 (s, H³²); ¹³C NMR (CDCl₃): δ=33.42 (t, C1), 108.38 (s, C2), 171.94 (s, C3), 35.01 (s, C4), 49.53 (d, C5), 18.16 (t, C6), 31.24 (t, C7), 45.75 (s, C8), 175.87 (c, C9), 41.09 (s, C10), 124.65 (d, C11), 200.77 (s, C12), 47.90 (d, C13), 41.79 (s, C14), 26.27 (t, C15), 26.13 (t, C16), 31.95 (s, C17), 37.85 (d, C18), 33.79 (t, C19), 43.95 (s, C20), 31.16 (t, C21), 38.18 (t, C22), 28.65 (q, C23), 21.26 (q, C24), 24.52 (q, C25), 23.28 (q, C26), 21.87 (q, C27), 26.99 (q, C28), 28.51 (q, C29), 177.26 (s, C30), 51.47 (q, C31), 150.06 (d, C32); HRMS: m/z calcd for C₃₂H₄₅NO₄: 507.7040; found: 507.3349.
The mixture of tautomers (11): Sodium methylate (11 g, 204 mmol) was added at 0°C to a solution of isoxazole 10 (3.0 g, 5.9 mmol) in methanol (85 mL) and diethyl ether (170 mL). The mixture was stirred at room temperature for 1 h. The resulting mixture was diluted with a mixture of chloroform/diethyl ether (1:3; 100 mL), and 5 % HCl was added to achieve pH<7. The organic layer was separated, and the aqueous layer was extracted with chloroform/diethyl ether (1:3; 3×50 mL). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (3×50 mL) and brine (3×50 mL), and dried over magnesium sulfate. The solvent was removed to give a mixture of tautomers 11 (yield=3.0 g, 100 %). This material was used for the next reaction without further purification. HRMS: m/z calcd for C₃₂H₄₅NO₄: 507.7040; found: 507.3349.
Methyl 2-cyano-3,12-dioxo-18βH-olean-9(11),1(2)-dien-30-oate (12): Mixture 11 (2.8 g, 5.5 mmol) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (1.5 g, 6.5 mmol) in dry benzene (160 mL) were heated under reflux for 4 h. Insoluble matter was removed by filtration, and the filtrate was evaporated in a vacuum to give a solid. The solid was subjected to flash column chromatography (silica gel; benzene followed by benzene/acetone (10:1)) to give crude 12. The crude product was purified by recrystallization from methanol/chloroform to give crystals 12 (yield 1.7 g, 61 %). M. p. 247–249°C; ¹H NMR (CDCl₃): δ=0.90 (s, 3 H; C28-H₃), 0.96 (s, 3 H; C27-H₃), 1.09 (s, 3 H; C29-H₃), 1.14 (s, 3 H; C24-H₃), 1.22 (s, 3 H; C23-H₃), 1.44 C (s, 3 H; C26-H₃), 1.47 (s, 3 H; C25-H₃), 0.93 (dm, ²J(H^16e,H^16a)=13.3 Hz; H^16e), 1.08 (m, H^15e), 1.20 (dd, ²J(H^19a,H^19e)=13.2, ³J(H^19a,H¹⁸)=13.2 Hz; H^19a), 1.18–1.32 (m, 2 H; H^21a, H^22e), 1.48 (ddd, ²J(H^22a,H^22e)=14.0, ³J(H^22a,H^21a)=14.0, ³J(H^22a,H^21e)=4.2 Hz; H^22a), 1.55 (dm, ²J(H^7e,H^7a)=13.5 Hz; H^7e), 1.67–1.79 (m, 4 H; H^5a, 2 H⁶, H^7a), 1.82 (m, H^15a), 1.87 (m, H^16a), 1.94 (dddd, ²J(H^21e,H^21a)=13.3, ³J(H^21a,H^22a)=4.2, ³J(H^21e,H^22e)=3.2, ⁴J(H^21e,H^19e)=2.8 Hz; H^21e), 2.02 (ddd, ³J(H¹⁸,H^19a)=13.2, ³J(H¹⁸,H¹³)=4.7, ³J(H¹⁸,^19e)=3.2 Hz; H¹⁸), 2.17 (ddd, ²J(H^19e,H^19a)=13.2, ³J(H^19e,H¹⁸)=3.2, ⁴J(H^19e,H^21e)=2.8 Hz; H^19e), 3.02 (d, ³J(H¹³,H¹⁸)=4.7 Hz; H¹³), 3.72 (s, 3 H; OC31-H₃), 5.97 (s, H¹¹), 8.01 (s, H¹); ¹³C NMR (CDCl₃): δ=165.65 (d, C1), 114.46 (s, C2), 196.42 (s, C3), 44.86 (s, C4), 47.57 (d, C5), 18.12 (t, C6), 31.58 (t, C7), 45.82 (s, C8), 168.18 (s, C9), 42.36 (s, C10), 124.17 (d, C11), 199.52 (s, C12), 48.04 (d, C13), 42.10 (s, C14), 26.03 (t, C15), 26.00 (t, C16), 31.88 (s, C17), 37.75 (d, C18), 33.61 (t, C19), 43.91 (s, C20), 31.11 (t, C21), 38.14 (t, C22), 26.88 (q, C23), 21.40 (q, C24), 26.61 (q, C25), 24.77 (q, C26), 21.81 (q, C27), 26.96 (q, C28), 28.46 (q, C29), 177.13 (s, C30), 51.48 (q, C31), 114.22 (s, C32); HRMS: m/z calcd for C₃₂H₄₃NO₄: 505.6881; found: 505.3192.
Cell culture and glycyrrhetinic acids derivatives: Human KB-3-1 epidermoid carcinoma cell line, HeLa cervical epithelioid carcinoma cell line, MCF-7 breast adenocarcinoma cell line, SKNMC neuroblastoma cell line (Russian Cell Culture Collection, St. Petersburg), KB-8-5 multidrug resistant cancer cell line (kindly provided by Professor M. Gottesman (NIH, USA)), were cultured in DMEM supplemented with 10 % (v/v) heat-inactivated fetal bovine serum, penicillin (100 U mL⁻¹; ICN Biomedicals, Inc), streptomycin (100 μg mL⁻¹) and amphotericin (250 μg mL⁻¹). Cells were maintained in a humidified atmosphere (5 % CO₂, 37°C). The KB-8-5 cell line was incubated in the additional presence of vinblastine (300 nmoll⁻¹).
Glycyrrhetinic acids derivatives were dissolved in DMSO (10 mmoll⁻¹), and stock solution were stored at −20°C.
After treatments, both floating and adherent scraped cells were collected by centrifugation, and used for further analysis.
Cell viability analysis by MTT assay: Cancer cells, growing in log phase, were seeded in triplicate 96-well plates at a density of 5×10³ cells per well for HeLa cells, 7×10³ for KB-3-1, KB-8-5 and MCF-7 cells, and 30×10³ for SKNMC cells. The plates were incubated at 37°C in humidified 5 % CO₂ atmosphere. Cells were allowed to adhere to the surface for 24 h, then treated with varying doses of the compounds for 24 h. Aliquots of [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) solution (10 μL, 5 mg mL⁻¹) were added to each well, and the incubation was continued for an additional 3 h. The dark blue formazan crystals (formed within healthy cells) were solubilized with DMSO, and the absorbance was measured at 570 nm in a Multiscan RC plate reader (Thermo LabSystems, Finland). The IC₅₀ was determined as the compound concentration required to decrease the A₅₇₀ to 50 % of the control (no compound, DMSO), and was determined by interpolation from dose-response curves.
Analysis of antioxidant effect on the cytotoxicity of compound 12: KB-3-1 cells growing in the log phase were seeded in triplicate in 96-well plates (7×10³ cells per well). The plates were incubated at 37°C in a humidified 5 % CO₂ atmosphere. Cells were allowed to adhere to the surface for 24 h, then treated with GSH (1, 5, 15 or 45 mm) or with ascorbic acid (1, 3 or 5 mm), both alone and in combination with 12 (1 μm). Cells were incubated with the compounds for 24 h and cell viability was analyzed by the MTT assay as described above.
Morphological observation of nuclear change: KB-3-1 cells were seeded into 24-well plates (10⁵ cells per well) containing glass cover slips. Cells were allowed to adhere to the surface for 24 h. Cells were treated with 12 (1 μm) or with DMSO (0.1 % (v/v)) for 6, 18 or 24 h at 37°C in a humidified 5 % CO₂ atmosphere. After incubation, cells were fixed with 4 % formaldehyde for 15 min, and then stained for 30 min with Hoechst 33258 (200 ng mL⁻¹). Cells were analyzed for the presence of fragmented nuclei and condensed chromatin by fluorescent microscopy.
Apoptosis detection by Annexin V staining: Log-phase KB-3-1 cells in six-well plates (5×10⁵ cells per well) were treated with 12 (0.3 μm or 1 μm) or with DMSO (0.1 % (v/v)) for 4, 18 or 24 h. The cells were stained with Annexin V-FITC and propidium iodide by using the ApopNexin-FITC apoptosis detection kit (Chemicon Millipore) according to the manufacturer's instructions. Briefly, cells were collected by scraping, washed twice with cold PBS, and centrifuged (400 g, 5 min). Cells were resuspended in binding buffer (1 mL) at a concentration of 1×10⁶ cells per mL, then a sample (200 μL) was transferred to a 5 mL culture tube, and Annexin V-FITC (3 μL) and 100×PI (2 μL) were added. Cells were incubated for 15 min at room temperature in the dark. Finally, binding buffer (300 μL) was added to each tube, and the quantity of apoptotic cells in samples was analyzed by flow cytometry (FC500, Beckman Coulter, USA). For each sample, 10 000 ungated events were acquired. Annexin V⁺/PI⁻ cells represented early apoptotic populations. Annexin V⁺/PI⁺ cells represented either late apoptotic or secondary necrotic populations.
Mitochondria depolarization analysis: Mitochondria involvement in apoptosis was measured by the mitochondrial depolarization that occurs early during the onset of apoptosis. KB-3-1 cells were treated with 1 (1 μm), 12 (1 μm) or DMSO (0.1 % (v/v)) for 6 h, and loss of mitochondrial potential was determined by using the mitochondrial potential sensor JC-1 (Molecular Probes, Invitrogen).
Flow cytometry assay: Cells were incubated for the appropriate time with the compounds, then collected, incubated in complete media in the dark with JC-1 (5 μg mL⁻¹) at 37°C for 15 min, and washed with PBS. At the end of the incubation period the cells were washed twice with cold PBS, and resuspended in PBS (400 μL). J-aggregate and J-monomer fluorescence were recorded in the channesl 2 (FL2) and 1 (FL1), respectively, of an FC500 flow cytometer. Necrotic fragments were electronically gated out, on the basis of morphological characteristics on the forward light scatter versus side light scatter dot plot.
Fluorescent microscopy assay: Cells were plated into 24-well plates (10⁵ cells per well) containing glass cover slips, and allowed to adhere to the surface for 24 h. Cells were incubated for the appropriate time with the compounds. After incubation the cell culture media was removed and replaced with JC-1 reagent (5 μm) diluted in PBS. Cells were incubated at 37°C in a 5 % CO₂ incubator for 15 min, and analyzed by fluorescence microscopy.
Cytofluorimetric analysis of DNA content: Exponentially growing KB-3-1 cells in 6-well plates (5×10⁵ cells per well) were treated with 12 (0.3 μm, or 1 μm) or DMSO (0.1 % (v/v)) for 18 h. After incubation, the cells were collected by centrifugation (400 g, 10 min), fixed with ice-cold 70 % ethanol for at least 1 h at 4°C and treated with RNase A from bovine pancreas (1 mg mL⁻¹; Sigma) for 30 min at 37°C. PI (50 μg mL⁻¹) was then added to the solution and the DNA content was quantitated by a flow cytometry. Cells in sub-G1 phase were considered apoptotic.
Analysis of caspase activation: After treatment of KB-3-1 cells with 1 (0.3 μm, 1 μm), or 12 (0.3 μm, 1 μm), or DMSO (0.1 % (v/v)) for 18 h, caspase activation was assayed by using the CaspACE FITC-VAD-FMK in situ marker (Promega).
Flow cytometry assay: Cells were incubated for the appropriate time in the presence of the compounds, collected, suspended in PBS (0.5 mL), and FITC-VAD-FMK (1 μL, 5 mm) was added. The cells were gently mixed and incubated for 20 min at RT in the dark. Cells were washed twice with PBS, and the pellets resuspended in PBS (0.5 mL). Flow cytometry was conducted within 10 min.
Fluorescent microscopy assay: Cells were seeded (10⁵ cells per well) into 24-well plates containing glass cover slips, and allowed to adhere to the surface for 24 h. After incubation for the appropriate time with the compounds, the cell culture medium was removed and replaced with JC-1 reagent (5 μm) diluted in PBS. Cells were incubated at 37°C in a 5 % CO₂ incubator for 15 min. The cells were washed twice with PBS, and caspase activation was analyzed by fluorescence microscopy within 10 min.

Logashenko E.B., Salomatina O.V., Markov A.V., Korchagina D.V., Salakhutdinov N.F., Tolstikov G.A., Vlassov V.V, & Zenkova M.A. (2011). Synthesis and Pro-Apoptotic Activity of Novel Glycyrrhetinic Acid Derivatives. Chembiochem, 12(5), 784-794.

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Publication 2011

Synthesis of Indolo[2,3-d]benzazepinone Derivatives

Cited 7 times

2-Iodobenzonitrile, ethyl-1H-indole-carboxylate and 5-bromo-ethyl-1H-indole-carboxylate were purchased from ABCR. Borane solution (1M in THF), absolute DMF, dimethylaminopyridine, di-tert-butyl-dicarbonate, absolute acetonitrile, palladium(II) acetate, sodium bicarbonate, basic aluminuim oxide, 2-acetylpyridine and 2-formylpyridine were bought from Fisher/Acros Organics. Ethoxy-methylchloride was obtained form TCI. Sodium hydride, phosphorus(V) sulfide, celite, hydrazine monohydrate and methyl iodide were purchased from Sigma Aldrich, while lithium hydroxide monohydrate and triphenylphosphine were from Alfa Aesar. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide-hydrochloride was purchased from IRIS biotech. Silver(I) carbonate was purchased from Merck. 2-Iodobenzylamine was prepared by a known method.^{26 (link)} The unsubstituted indolo[2,3-d]benzazepinone (A) was prepared by following published protocols.^{18 (link)–20} The 11-bromo-substituted B was prepared using reported precedures,^{18 (link)–20} with some modifications, a detailed description of the synthesis of B is given in the Supplementary Information file.

Bacher F., Wittmann C., Nové M., Spengler G., Marć M.A., Enyedy E.A., Darvasiova D., Rapta P., Reiner T, & Arion V.B. (2019). Novel latonduine derived proligands and their copper(II) complexes show cytotoxicity in the nanomolar range in human colon adenocarcinoma cells and in vitro cancer selectivity. Dalton transactions (Cambridge, England : 2003), 48(28), 10464-10478.

Publication 2019

2-acetylpyridine Acetate acetonitrile Anabolism Bicarbonate, Sodium bis(tert-butoxycarbonyl)oxide Boranes Carbodiimides Carbonates Celite hydrazine hydrate indole Iris Plant lithium hydroxide monohydrate Methyl Chloride methyl iodide Oxides Palladium Phosphorus Silver sodium hydride Sulfides triphenylphosphine

Simultaneous Extraction and Quantification of 25(OH)D3 and 25(OH)D2 in Serum

Cited 7 times

Serum materials from three individual donors were used for 25(OH)D₃ studies (6.3 ng/g, 15.3 ng/g, and 27.0 ng/g 25(OH)D₃ for sera 1, 2, and 3, respectively), while a serum material from a single donor was used for 25(OH)D₂ studies [0.9 ng/g 25(OH)D₂]. Samples were prepared in three different sets (each on a different day), each set consisting of triplicate aliquots from each of the serum materials. Each serum material was accurately weighed (approximately 2 g) into a 50 mL glass centrifuge tube. Each sample was then spiked with appropriate weighed amounts of 25(OH)D₃-d₃ and 25(OH)D₂-d₃ to get an approximately 1:1 mass ratio of analyte to internal standard. After equilibration at room temperature for 1 h, the pH of each sample was adjusted to pH 9.8 ± 0.2 with approximately 400 μL of 0.1 g/mL carbonate buffer, pH 9.8 (approximately 200 μL of buffer per mL of liquid). The 25(OH)D₃ and 25(OH)D₂ were simultaneously extracted from the serum matrix with 8 mL of hexane-ethyl acetate (50:50, volume fraction). Each sample was shaken vigorously for 10 min using a mechanical shaker to allow complete mixing. The upper hexane-ethyl acetate layer was transferred to another 50 mL centrifuge tube. Hexane-ethyl acetate extraction was repeated once more with another 8 mL of solvent by shaking for 3 min. The combined extracts were dried under nitrogen at 45 °C and the residue was reconstituted with 120 μL of methanol for LC-MS/MS analysis.
Preliminary experiments were conducted to evaluate the 25(OH)D concentrations of serum materials. An initial experiment was performed where arbitrary amounts of the internal standard were chosen, and a wider range of mass ratios (0.2 to 3.0) for the standards was used. Once the approximate 25(OH)D concentration was determined, the quantity of internal standard was calculated to obtain a 1:1 mass ratio.

Tai S.S., Bedner M, & Phinney K.W. (2010). Development of a Candidate Reference Measurement Procedure for the Determination of 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in Human Serum Using Isotope-Dilution Liquid Chromatography/Tandem Mass Spectrometry. Analytical chemistry, 82(5), 1942-1948.

Publication 2010

Buffers Calcifediol Carbonates Donors ethyl acetate Methanol n-hexane Nitrogen Serum Solvents Tandem Mass Spectrometry Tissue Donors

Most recents protocols related to «Ethyl carbonate»

Synthesis of Azithromycin Chloramphenicol Conjugate

A solution of the compound 3 (0.91 g, 1.00 mmol), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 0.30 mL, 2.00 mmol) and 1,2-diaminoethane (0.20 g, 3.00 mmol) in DMF (10 mL) was stirred for 2 h at room temperature. The reaction mixture was diluted with 5% aqueous NaHCO₃ (20 mL), and the product was extracted with ethyl acetate (3 × 15 mL). The combined organic layers were washed with brine (15 mL), and dried over Na₂SO₄. The solvent was evaporated, yielding 2′-O-acetyl-4′′-O-((2-aminoethyl)carbamoyl)-11,12-cyclic carbonate of azithromycin as a white solid, which was used for the next step without purification.
The crude powder of 2′-O-acetyl-4′′-O-((2-aminoethyl)carbamoyl)-11,12-cyclic carbonate of azithromycin was dissolved in DMF (5 mL) and added to the solution of chloramphenicol hemisuccinate [31 (link)] (0.47 g, 1.1 mmol), DIPEA (0.52 mL, 3 mmol), and PyBOP (0.78 g, 1.5 mmol) in DMF (5 mL). The reaction mixture was stirred for 1 h at room temperature, and diluted with 5% aqueous NaHCO₃ solution (10 mL). The product was extracted with ethyl acetate (3 × 15 mL), the combined organic layers were washed with brine (10 mL), dried over Na₂SO₄, and the solvent was evaporated. The crude residue was purified via column chromatography (CHCl₃:MeOH, 15:1) to give 0.26 g (20%) of compound 4a as a white powder; R_f = 0.31 (DCM/MeOH, 7:1). HPLC: t_R = 13.6 min (system A). ¹H and ¹³C NMR spectra are given in Table S1 and Figures S19 and S20, Supplementary Materials. HRMS (ESI) calculated for C₅₉H₉₃Cl₂N₆O₂₂ [M + H]⁺: 1307.5715; found: 1307.5711 (Figure S4, Supplementary Materials).

Volynkina I.A., Bychkova E.N., Karakchieva A.O., Tikhomirov A.S., Zatonsky G.V., Solovieva S.E., Martynov M.M., Grammatikova N.E., Tereshchenkov A.G., Paleskava A., Konevega A.L., Sergiev P.V., Dontsova O.A., Osterman I.A., Shchekotikhin A.E, & Tevyashova A.N. (2024). Hybrid Molecules of Azithromycin with Chloramphenicol and Metronidazole: Synthesis and Study of Antibacterial Properties. Pharmaceuticals, 17(2), 187.

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Publication 2024

Electrochemical Performance with Electrolyte Additives

All electrochemical tests were
performed with 1 M lithium hexafluorophosphate (LiPF₆)
in ethylene carbonate and ethyl methyl carbonate electrolyte (EC:EMC,
30:70 wt %) with 2 wt % vinylene carbonate (VC) additive (Elyte, Germany);
for the REs test, ferrocene (≥99% purity, AlfaAesar, Germany)
was added to the same electrolyte to obtain a 1 mM solution. The detailed
description of WE, CE, and RE preparation procedures is available
in the Supporting Information.

Sanin A, & Stein H.S. (2024). Exploring Reproducible Nonaqueous Scanning Droplet Cell Electrochemistry in Model Battery Chemistries. Chemistry of Materials, 36(8), 3536-3545.

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Publication 2024

Electrode Materials Synthesis and Evaluation

The sodium dodecylbenzene sulfonate (SDBS, 98%) and TAPB (99.67%) were purchased from Tianjin Damao Chemical Reagent Factory, while BTMB (99.98%) and TP (97%) were obtained from Jilin Province Yanshen Technology Co, Ltd. BPY (97%) and glacial acetic acid (99.5%) were procured from Shanghai Macklin Biochemical Co, Ltd. Electrolytes (1 M LiPF₆) in ethylene carbonate (EC)/dimethyl carbonate (DMC)/ethyl methyl carbonate (EMC) (volume ratio of 1:1:1) and CR2032 coin type cells were purchased from DoDochem.

Xu X., Zhang J., Zhang Z., Lu G., Cao W., Wang N., Xia Y., Feng Q, & Qiao S. (2024). All-Covalent Organic Framework Nanofilms Assembled Lithium-Ion Capacitor to Solve the Imbalanced Charge Storage Kinetics. Nano-Micro Letters, 16, 116.

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Publication 2024

Standardizing Na2CO3 Titrations

Not available on PMC !

Sodium carbonate (Na2CO3), sodium hydroxide, phenolphthalein, sulfamic acid, and 95% ethyl alcohol were purchased from Dalkem Corporation. The reagents that were used are of high purity and were used without further purification. All the solutions were prepared as aqueous solutions. The different concentrations of Na2CO3 were prepared using freshly boiled distilled water and expressed as calcium carbonate (CaCO3) concentration.

Parungao C.A.C., & Reyes D.F. (2024). RGB-based colorimetric method for the analysis of water alkalinity using Cordyline fruticosa extracts as visual indicator. International Journal of Public Health Science (IJPHS), 13(1), 369-369.

Publication 2024

Phytochemical Profiling and Antioxidant Assays

Not available on PMC !

Distilled water, rectified ethyl alcohol 96% V/V, sodium carbonate (Carl Roth GmbH & Co, Karlsruhe, Germany), Folin-Ciocalteu reagent (Sigma Aldrich, St. Louis, USA), gallic acid monohydrate (Sigma Aldrich, St. Louis, USA), hydrochloric acid (Sigma Aldrich, Germany), DMAC (4-dimethylaminocinnamaldehyde) (Sigma Aldrich, Germany), epicatechin (Sigma Aldrich, Germany), ABTS (2,2'-Azino-di(3-ethyl-benzthiazoline sulphonic acid ( 6

Daukšienė J., Burdulienė K., Daukšys G., Paulauskaitė L., & Burdulis D. (2024). The influence of raw material preparation on the yield of bioactive substances in lingonberry (Vaccinium vitis-idaea L.) fruits. Chemija, 35(1).

Publication 2024

Top products related to «Ethyl carbonate»

Ethyl acetate by Merck Group

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Ethyl acetate is a clear, colorless liquid solvent commonly used in laboratory applications. It has a characteristic sweet, fruity odor. Ethyl acetate is known for its ability to dissolve a variety of organic compounds, making it a versatile tool in chemical research and analysis.

Gallic acid by Merck Group

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Gallic acid is a naturally occurring organic compound that can be used as a laboratory reagent. It is a white to light tan crystalline solid with the chemical formula C6H2(OH)3COOH. Gallic acid is commonly used in various analytical and research applications.

Sodium carbonate by Merck Group

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Sodium carbonate is a water-soluble inorganic compound with the chemical formula Na2CO3. It is a white, crystalline solid that is commonly used as a pH regulator, water softener, and cleaning agent in various industrial and laboratory applications.

Methanol by Merck Group

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Methanol is a clear, colorless, and flammable liquid that is widely used in various industrial and laboratory applications. It serves as a solvent, fuel, and chemical intermediate. Methanol has a simple chemical formula of CH3OH and a boiling point of 64.7°C. It is a versatile compound that is widely used in the production of other chemicals, as well as in the fuel industry.

Folin ciocalteu reagent by Merck Group

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The Folin-Ciocalteu reagent is a colorimetric reagent used for the quantitative determination of phenolic compounds. It is a mixture of phosphomolybdic and phosphotungstic acid complexes that undergo a color change when reduced by phenolic compounds.

Acetonitrile by Merck Group

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Acetonitrile is a colorless, volatile, flammable liquid. It is a commonly used solvent in various analytical and chemical applications, including liquid chromatography, gas chromatography, and other laboratory procedures. Acetonitrile is known for its high polarity and ability to dissolve a wide range of organic compounds.

Sodium hydroxide (naoh) by Merck Group

Sourced in Germany, United States, India, United Kingdom, Italy, China, Spain, France, Australia, Canada, Poland, Switzerland, Singapore, Belgium, Sao Tome and Principe, Ireland, Sweden, Brazil, Israel, Mexico, Macao, Chile, Japan, Hungary, Malaysia, Denmark, Portugal, Indonesia, Netherlands, Czechia, Finland, Austria, Romania, Pakistan, Cameroon, Egypt, Greece, Bulgaria, Norway, Colombia, New Zealand, Lithuania

Sodium hydroxide is a chemical compound with the formula NaOH. It is a white, odorless, crystalline solid that is highly soluble in water and is a strong base. It is commonly used in various laboratory applications as a reagent.

2 2 diphenyl 1 picrylhydrazyl (dpph) by Merck Group

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DPPH is a chemical compound used as a free radical scavenger in various analytical techniques. It is commonly used to assess the antioxidant activity of substances. The core function of DPPH is to serve as a stable free radical that can be reduced, resulting in a color change that can be measured spectrophotometrically.

Hydrochloric acid (hcl) by Merck Group

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Hydrochloric acid is a commonly used laboratory reagent. It is a clear, colorless, and highly corrosive liquid with a pungent odor. Hydrochloric acid is an aqueous solution of hydrogen chloride gas.

Ethanol by Merck Group

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Ethanol is a clear, colorless liquid chemical compound commonly used in laboratory settings. It is a key component in various scientific applications, serving as a solvent, disinfectant, and fuel source. Ethanol has a molecular formula of C2H6O and a range of industrial and research uses.

What is Ethyl carbonate?

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What are some common applications of Ethyl carbonate?

Ethyl carbonate is used in a variety of applications, including as a solvent, an intermediate in organic synthesis, and a co-solvent in some cosmetic and personal care products. It is also used in the production of certain plastics and as a fuel additive. Due to its relatively low toxicity and eco-friendly nature, Ethyl carbonate is considered a versatile and useful chemical compound.

Are there any safety considerations when working with Ethyl carbonate?

While Ethyl carbonate is generally considered a safe and eco-friendly chemical, there are still some safety considerations to keep in mind. It is a flammable liquid, so proper precautions should be taken to avoid ignition sources. Additionally, Ethyl carbonate should be handled in a well-ventilated area, as the vapors can be irritating to the eyes and respiratory system. As with any chemical, it's important to follow all applicable safety protocols and wear appropriate personal protective equipment when working with Ethyl carbonate.

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PubCompare.ai's AI-driven platform can help you identify the most effective protocols and procedures for using Ethyl carbonate in your research. The tool can scree protocol literature more efficiently, and use AI to pinpoit critical insights that help you choose the best option for reproducibility and accuracy. By leveraging PubCompare.ai, you can save time, enhance the quality of your research, and improve your overall outcomes when working with Ethyl carbonate.

Ethyl carbonate

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