2136-75-6Relevant articles and documents
Substituted dienes prepared from betulinic acid – Synthesis, cytotoxicity, mechanism of action, and pharmacological parameters
Frydrych, Ivo,Urban, Milan,?arek, Jan,Benická, Sandra,D?ubák, Petr,Gurská, Soňa,Hajdúch, Marián,Kotulová, Jana,Li?ková, Barbora,Olejníková, Denisa,Pokorny, Jan
, (2021/07/28)
A set of new substituted dienes were synthesized from betulinic acid by its oxidation to 30-oxobetulinic acid followed by the Wittig reaction. Cytotoxicity of all compounds was tested in vitro in eight cancer cell lines and two noncancer fibroblasts. Almost all dienes were more cytotoxic than betulinic acid. Compounds 4.22, 4.30, 4.33, 4.39 had IC50 below 5 μmol/L; 4.22 and 4.39 were selected for studies of the mechanism of action. Cell cycle analysis revealed an increase in the number of apoptotic cells at 5 × IC50 concentration, where activation of irreversible changes leading to cell death can be expected. Both 4.22 and 4.39 led to the accumulation of cells in the G0/G1 phase with partial inhibition of DNA/RNA synthesis at 1 × IC50 and almost complete inhibition at 5 × IC50. Interestingly, compound 4.39 at 5 × IC50 caused the accumulation of cells in the S phase. Higher concentrations of tested drugs probably inhibit more off-targets than lower concentrations. Mechanisms disrupting cellular metabolism can induce the accumulation of cells in the S phase. Both compounds 4.22 and 4.39 trigger selective apoptosis in cancer cells via intrinsic pathway, which we have demonstrated by changes in the expression of the crucial apoptosis-related protein. Pharmacological parameters of derivative 4.22 were superior to 4.39, therefore 4.22 was the finally selected candidate for the development of anticancer drug.
Synthesis of 9- and 12-nitro conjugated linoleic acid: Regiospecific isomers of naturally occurring conjugated nitrodienes
Woodcock, Steven R.,Salvatore, Sonia R.,Freeman, Bruce A.,Schopfer, Francisco J.
supporting information, (2021/09/13)
Conjugated diene-containing fatty acids (rumenic and rumelenic acids) are major substrates for nitration under physiological conditions. Their nitrated products are present in human urine. These nitrodiene-containing lipid electrophiles contain a strongly electron-withdrawing pair of conjugated double bonds amenable to nucleophilic attack in biological milieu, which affords them pluripotent signaling capabilities. We report synthetic methods to obtain useful quantities of three main biological nitrated fatty acids (9- and 12-nitro-conjugated linoleic acids and 9-nitro-conjugated linolenic acid) in six or seven steps from commercially available starting materials, for biological evaluation of these naturally occurring biomolecules.
Method for preparing formyl methylene triphenylphosphine
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Paragraph 0008; 0019-0020; 0024-0026; 0030, (2020/12/14)
The invention discloses a method for preparing formyl methylene triphenylphosphine. The method comprises the following steps: reacting triphenylphosphine with excessive chloroacetaldehyde dimethyl acetal under the catalysis of a proper catalyst to obtain corresponding quaternary phosphonium salt; dissolving quaternary phosphonium salt in water, adding a trace amount of inorganic acid to hydrolyzethe quaternary phosphonium salt, dropwise adding the hydrolyzed quaternary phosphonium salt into an aqueous solution of alkali according to a conventional method, and filtering and washing precipitates to directly obtain formyl methylene triphenylphosphine. The method has the advantages of no use of expensive reagents, simple operation, high yield, less three wastes, and easy realization of industrialization.
Method for preparing (formylmethylene)triphenylphosphorane
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Paragraph 0006; 0009; 0010; 0011; 0014; 0015; 0016; 0019, (2019/10/01)
The present invention relates to a method for preparing (formylmethylene)triphenylphosphorane (further named (triphenylphosphoranylidene)acetaldehyde, CAS:2136-75-6). According to the method, a chloroacetaldehyde aqueous solution is directly added to a triphenylphosphine solution in a dropwise manner; part of the water in the chloroacetaldehyde is taken out through the azeotropy of the ester and the water, and the remaining water is consumed through the hydrolysis of the ester; the obtained quaternary phosphonium salt is dissolved in water according to a conventional method, the dissolved solution is added to an alkali aqueous solution in a dropwise manner; and the precipitate is filtered to obtain the (formylmethylene)triphenylphosphorane. According to the present invention, the method does not use expensive reagents, directly uses the chloroacetaldehyde aqueous solution, has characteristics of mild reaction conditions, simple operation, high yield and less three-waste, and is suitable for industrial production.
Preparation method of (formylmethylene) triphenyl orthophosphonium
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Paragraph 0019; 0029; 0046-0050, (2018/03/25)
The invention discloses a preparation method of (formylmethylene) triphenyl orthophosphonium, and relates to the technical field of chemical substance preparation. The preparation method specificallycomprises the following steps of: carrying out a hydrolysis reaction on 2-bromo-1,1-dimethoxyethane under an acidic condition to obtain 1-bromoacetaldehyde; reacting 1-bromoacetaldehyde with triphenylphosphine to obtain a transition state intermediate quaternary phosphine salt namely 2-aldehyde ethyl triphenylphosphine bromide; and adding alkali into an aprotic solvent to obtain a product namely (formylmethylene) triphenyl orthophosphonium by losing one molecule of hydrogen bromide. The preparation method provided by the invention has the advantages of short synthesis route, easy synthesis, simple operation, cheap and easily obtained raw materials, less side reactions, high yield and high purity of the prepared (formylmethylene) triphenyl orthophosphonium, and is suitable for industrial production.
Synthesis of Polysubstituted Pyridines via a One-Pot Metal-Free Strategy
Wei, Hongbo,Li, Yun,Xiao, Ke,Cheng, Bin,Wang, Huifei,Hu, Lin,Zhai, Hongbin
supporting information, p. 5974 - 5977 (2016/01/09)
An efficient strategy for the one-pot synthesis of polysubstituted pyridines via a cascade reaction from aldehydes, phosphorus ylides, and propargyl azide is reported. The reaction sequence involves a Wittig reaction, a Staudinger reaction, an aza-Wittig reaction, a 6π-3-azatriene electrocyclization, and a 1,3-H shift. This protocol provides quick access to the polysubstituted pyridines from readily available substrates in good to excellent yields.
Scope and limitations of 1,3,5-hexatriene derivatives in regioselective cobalt-catalyzed reactions
Schmidt, Anastasia,Hilt, Gerhard
supporting information, p. 2708 - 2711 (2013/07/26)
Applications of 1,3,5-hexatriene derivatives in atom-economic cobalt-catalyzed transformations, such as the Diels-Alder reaction with alkynes, the 1,4-hydrovinylation reaction with terminal alkenes, and the 1,4-hydrohexatrienylation reaction, are investigated. In all cases, regioselective transformations were found to generate cyclic derivatives such as stilbenes or acyclic products with a high control of the double bond geometry in the skipped trienes derived from the 1,4-hydrovinylation process or the tetraenes generated in the so far unprecedented 1,4-hydrohexatrienylation reaction.
Synthesis and biological activity of alkylidene-substituted cephems and penams
Potorocina,Vorona,Shestakova,Domracheva,Liepinsh,Veinberg
experimental part, p. 767 - 775 (2012/02/01)
The condensation of tert-butyl esters of 3-methyl-7-oxoceph-3-em-4- carboxylic and 6-oxopenicillanic acids with a series of 2- oxoalkylidene(triphenyl)phosphoranes gave tert-butyl esters of new cephalosporin and penicillin analogs with an alkylidene substituent in the β-lactam ring. Most of these products were oxidized by meta-chloroperbenzoic acid to the corresponding sulfones. The cephemes and penams synthesized including the oxidized products displayed high cytotoxicity relative to cancer cells in vitro. Some of the alkylidene-substituted cephems as the free acids, similar to Tazobactam, inhibit the catalytic activity of Enterobacter cloacae penicillinase.
Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl- 4(1H)-quinolones
Wube, Abraham A.,Hüfner, Antje,Thomaschitz, Christina,Blunder, Martina,Kollroser, Manfred,Bauer, Rudolf,Bucar, Franz
experimental part, p. 567 - 579 (2011/03/17)
A series of 23 new 1-methyl-2-alkenyl-4(1H)quinolones have been synthesized and evaluated in vitro for their antimycobacterial activities against fast growing species of mycobacteria, such as Mycobacterium fortuitum, M. smegmatis and M. phlei. The compounds displayed good to excellent inhibition of the growth of the mycobacterial test strains with improved antimycobacterial activity compared to the hit compound, evocarpine. The most active compounds, which possessed chain length of 11-13 carbons at position-2 displayed potent inhibitory effects with an MIC value of 1.0 mg/L. In a human diploid embryonic lung cell line, MRC-5 cytotoxicity assay, the alkaloids showed weak to moderate cytotoxic activity. Biological evaluation of these evocarpine analogues on the less pathogenic fast growing strains of mycobacteria showed an interesting antimycobacterial profile and provided significant insight into the structure-activity relationships.
Stereoselective synthesis of isomers of the naturally occurring 13-hydroxy-2,4,9-tetradecatrienoic acid. Part II [1]
Huefner, Antje,Hoeller, Christa,Reznicek, Gottfried
, p. 447 - 459 (2007/10/03)
The stereoselective syntheses of four unsaturated hydroxy fatty acids (13S,2E,4E,9E)-13-hydroxy-2,4,9-tetradecatrienoic acid, (13S,9Z,11E)-13-hydroxy- 9,11-tetradecadienoic acid, (13S,9E, 11E)-13-hydroxy-9,11-tetradecadienoic acid, and (13S,2E,4E,9E)-13-hydroxy-2,4,9,11-tetradecatrienoic acid, are described. Wittig reactions, regioselective oxidation of dialcohol 3, and diastereomerization were used. Springer-Verlag 2004.
