19812-64-7Relevant articles and documents
Discovery and Pharmacological Studies of 4-Hydroxyphenyl-Derived Phosphonium Salts Active in a Mouse Model of Visceral Leishmaniasis
Manzano, José Ignacio,Cueto-Díaz, Eduardo J.,Olías-Molero, Ana Isabel,Perea, Ana,Herraiz, Tomás,Torrado, Juan J.,Alunda, José María,Gamarro, Francisco,Dardonville, Christophe
, p. 10664 - 10675 (2019)
We report the discovery of new 4-hydroxyphenyl phosphonium salt derivatives active in the submicromolar range (EC50 from 0.04 to 0.28 μM, SI > 10) against the protozoan parasite Leishmania donovani. The pharmacokinetics and in vivo oral efficacy of compound 1 [(16-(2,4-dihydroxyphenyl)-16-oxohexadecyl)triphenylphosphonium bromide] in a mouse model of visceral leishmaniasis were established. Compound 1 reduced the parasite load in spleen (98.9%) and liver (95.3%) of infected mice after an oral dosage of four daily doses of 1.5 mg/kg. Mode of action studies showed that compound 1 diffuses across the plasma membrane, as designed, and targets the mitochondrion of Leishmania parasites. Disruption of the energetic metabolism, with a decrease of intracellular ATP levels as well as mitochondrial depolarization together with a significant reactive oxygen species production, contributes to the leishmanicidal effect of 1. Importantly, this compound was equally effective against antimonials and miltefosine-resistant clinical isolates of Leishmania infantum, indicating its potential as antileishmanial lead.
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Stone
, p. 571 (1940)
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The Thermodynamics of the Micelle Formation of Sodium α,ω-Alkanediyl Disulfate
Ikeda, Kenji,Nakasima, Tomoko,Esumi, Kunio,Meguro, Kenjiro
, p. 578 - 580 (1989)
The critical micelle concentrations of a α,ω-type surfactant: (sodium α,ω-alkanediyl disulfate: n=12, 14, 16) in an aqueous solution have been determined by studying the electrical conductivity, and the free energies of the micelle formation have then been estimated from these data.The free energy of micelle formation of a α,ω-type surfactant was smaller than that of a normal-type surfactant with the same alkyl chain length as the α,ω-type one.The free-energy changes per -(CH2)-segment was also calculated from these data.It is found that the free-energy change per -(CH2)-segment of the α,ω-type surfactant is -11.1 -1>.
Non-metal-templated approaches to bis(borane) derivatives of macrocyclic dibridgehead diphosphines via alkene metathesis
Fiedler, Tobias,Barbasiewicz, Micha?,Stollenz, Michael,Gladysz, John A.
, p. 2354 - 2365 (2018)
Two routes to the title compounds are evaluated. First, a ca. 0.01 M CH2Cl2 solution of H3B·P((CH2)6CH=CH2)3 (1·BH3) is treated with 5 mol % of Grubbs' first generation catalyst (0 °C to reflux), followed by H2 (5 bar) and Wilkinson's catalyst (55 °C). Column chromatography affords H3B·P(n-C8H17)3 (1%), H3B·P((CH2)13CH2)(n-C8H17) (8%; see text for tie bars that indicate additional phosphorus–carbon linkages, which are coded in the abstract with italics), H3B·P((CH2)13CH2)((CH2)14)P((CH2)13CH2)·BH3 (6·2BH3, 10%), in,out-H3B·P((CH2)14)3P·BH3 (in,out-2·2BH3, 4%) and the stereoisomer (in,in/out,out)-2·2BH3 (2%). Four of these structures are verified by independent syntheses. Second, 1,14-tetradecanedioic acid is converted (reduction, bromination, Arbuzov reaction, LiAlH4) to H2P((CH2)14)PH2 (10; 76% overall yield). The reaction with H3B·SMe2 gives 10·2BH3, which is treated with n-BuLi (4.4 equiv) and Br(CH2)6CH=CH2 (4.0 equiv) to afford the tetraalkenyl precursor (H2C=CH(CH2)6)2(H3B)P((CH2)14)P(BH3)((CH2)6CH=CH2)2 (11·2BH3; 18%). Alternative approaches to 11·2BH3 (e.g., via 11) were unsuccessful. An analogous metathesis/hydrogenation/chromatography sequence with 11·2BH3 (0.0010 M in CH2Cl2) gives 6·2BH3 (5%), in,out-2·2BH3 (6%), and (in,in/out,out)-2·2BH3 (7%). Despite the doubled yield of 2·2BH3, the longer synthesis of 11·2BH3 vs 1·BH3 renders the two routes a toss-up; neither compares favorably with precious metal templated syntheses.
Synthesis of 13C-labelled cutin and suberin monomeric dicarboxylic acids of the general formula HO213C-(CH2)n-13CO2H (n = 10, 12, 14, 16, 18, 20, 22, 24, 26, 28)
Schink, Carina,Spielvogel, Sandra,Imhof, Wolfgang
, p. 14 - 29 (2020/11/30)
13C-labeled dicarboxylic acids HO213C-(CH2)n-13CO2H (n = 10, 12, 14, 16, 18, 20, 22, 24, 26, 28) have been synthesized as internal standards for LC-MS and GC-MS analysis of cutin and suberin monomer degradation by soil-based microorganisms. Different synthetic strategies had to be applied depending on the chain length of the respective synthetic target and because of economic considerations. 13C-labels were introduced by nucleophilic substitution of a suitable leaving group with labelled potassium cyanide and subsequent hydrolysis of the nitriles to produce the corresponding dicarboxylic acids. All new compounds are characterized by GC/MS, IR, and NMR methods as well as by elemental analysis.
