303-43-5Relevant articles and documents
Structural insights into the inhibition mechanism of human sterol O-acyltransferase 1 by a competitive inhibitor
Chang, Catherine C. Y.,Chang, Ta-Yuan,Chen, Lei,Chen, Si-Cong,Guan, Chengcheng,Kang, Yunlu,Luo, Tuoping,Nishi, Koji,Niu, Yange,Wu, Jing-Xiang
, (2020)
Sterol O-acyltransferase 1 (SOAT1) is an endoplasmic reticulum (ER) resident, multi-transmembrane enzyme that belongs to the membrane-bound O-acyltransferase (MBOAT) family. It catalyzes the esterification of cholesterol to generate cholesteryl esters for cholesterol storage. SOAT1 is a target to treat several human diseases. However, its structure and mechanism remain elusive since its discovery. Here, we report the structure of human SOAT1 (hSOAT1) determined by cryo-EM. hSOAT1 is a tetramer consisted of a dimer of dimer. The structure of hSOAT1 dimer at 3.5 ? resolution reveals that a small molecule inhibitor CI-976 binds inside the catalytic chamber and blocks the accessibility of the active site residues H460, N421 and W420. Our results pave the way for future mechanistic study and rational drug design targeting hSOAT1 and other mammalian MBOAT family members.
Synthesis and characterization of novel fatty acid analogs of cholesterol: In vitro antimicrobial activity
Banday, Mudasir R.,Farshori, Nida N.,Ahmad, Anis,Khan, Asad U.,Rauf, Abdul
, p. 1459 - 1464 (2010)
In the present study we synthesized, characterized and checked the antimicrobial activity of fatty acid analogs of cholesterol. The synthesized compounds were characterized using IR, 1H NMR, 13C NMR and mass spectral data and tested for their antimicrobial activity by disk diffusion assay with slight modifications against Gram-positive, Gram-negative strains of bacteria as well as fungal strains. Minimum inhibitory concentration (MIC) of all the synthesized compounds was also determined. Compounds 7-14 showed inhibitory action against both the groups of bacteria and four strains of fungus. In vitro antimicrobial activity of the test compounds show that the compounds 10 and 13 are excellent antibacterial agents, where as compounds 13 and 14 are the excellent antifungal agents among the eight synthesized compounds.
Macrolactonization Reactions Driven by a Pentafluorobenzoyl Group**
Ciofini, Ilaria,Force, Guillaume,Leb?uf, David,Mayer, Robert J.,Perfetto, Anna
supporting information, p. 19843 - 19851 (2021/08/13)
Macrolactones constitute a privileged class of natural and synthetic products with a broad range of applications in the fine chemicals and pharmaceutical industry. Despite all the progress made towards their synthesis, notably from seco-acids, a macrolactonization promoter system that is effective, selective, flexible, readily available, and, insofar as possible, compatible with manifold functional groups is still lacking. Herein, we describe a strategy that relies on the formation of a mixed anhydride incorporating a pentafluorophenyl group which, due to its high electronic activation enables a convenient access to macrolactones, macrodiolides and esters with a broad versatility. Kinetic studies and DFT computations were performed to rationalize the reactivity of the pentafluorophenyl group in macrolactonization reactions.
Analysis of Intact Cholesteryl Esters of Furan Fatty Acids in Cod Liver
Hammann, Simon,Wendlinger, Christine,Vetter, Walter
, p. 611 - 620 (2015/06/08)
Furan fatty acids (F-acids) are a class of natural antioxidants with a furan moiety in the acyl chain. These minor fatty acids have been reported to occur with high proportions in the cholesteryl ester fraction of fish livers. Here we present a method for the direct analysis of intact cholesteryl esters with F-acids and other fatty acids in cod liver lipids. For this purpose, the cholesteryl ester fraction was isolated by solid phase extraction (SPE) and subsequently analyzed by gas chromatography with mass spectrometry (GC/MS) using a cool-on-column inlet. Pentadecanoic acid esterified with cholesterol was used as an internal standard. GC/MS spectra of F-acid cholesteryl esters featured the molecular ion along with characteristic fragment ions for both the cholesterol and the F-acid moiety. All investigated cod liver samples (n = 8) showed cholesteryl esters of F-acids and, to a lower degree, of conventional fatty acids. By means of GC/MS-SIM up to ten F-acid cholesteryl esters could be determined in the samples. The concentrations of cholesteryl esters with conventional fatty acids amounted to 78-140 mg/100 g lipids (mean 97 mg/100 g lipids), while F-acid cholesteryl esters were present at 47-270 mg/100 g lipids (mean 130 mg/100 g lipids).
Direct esterification of carboxylic acids with alcohols catalyzed by Iron(III) acetylacetonate complex
Weng, Shiue-Shien,Chen, Fong-Kuang,Ke, Chih-Shueh
, p. 2615 - 2621 (2013/07/26)
Direct condensation of carboxylic acids and alcohols with electronic, steric, and functional group variations was carried out using the environmentally benign, moisture-stable, inexpensive, and recoverable iron(III) acetylacetonate [Fe(acac)3] as catalyst (5 mol%). This iron salt efficiently catalyzed the esterification of several primary and secondary alcohols in refluxing xylene, without the need for a dehydration reagent. The chemoselectivity of the proposed protocol was demonstrated by the selective esterification of primary alcohol functionality in racemic 1-phenylethane-1,2- diol with benzoic acid. The esterification was also applicable to unmasked α-hydroxyacid, guasiaromatic, heterocyclic, and N-protected amino acids. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
Transesterification catalyzed by iron(III) β-diketonate species
Weng, Shiue-Shien,Ke, Chih-Shueh,Chen, Fong-Kuang,Lyu, You-Fu,Lin, Guan-Ying
supporting information; experimental part, p. 1640 - 1648 (2011/04/17)
A practical and clean protocol for transesterification catalyzed by a 5 mol % cheap, non-toxic and moisture stable Fe(acac)3 or other iron(III) β-diketonate species in solvent, such as heptane under azeotropic condition is developed. A remarkable rate enhancement was observed upon the addition of 5 mol % of an inorganic base, such as Na2CO3, which suggests that faster formation of a dimeric μ-alkoxy-bridged iron(III) species under alkaline conditions facilitates catalytic turnover. This system provides smooth transesterification over a wide range of structurally diverse esters and alcohols without disturbing functional groups. In addition, the use of iron β-diketonate complexes as catalysts is more environmentally friendly, safer, and economical than other transition-metal catalysts. Preliminary mechanistic studies indicate that the active catalyst is likely a dimeric μ-alkoxy-bridged iron(III) species, as determined by X-ray crystallography of [Fe(dbm)2(O-n-Bu)]2 derived from the alcoholysis of Fe(dbm)3 under alkaline conditions.
Purification of recombinant acyl-coenzyme a:cholesterol acyltransferase 1 (ACAT1) from H293 cells and binding studies between the enzyme and substrates using difference intrinsic fluorescence spectroscopy
Chang, Catherine C. Y.,Miyazaki, Akira,Dong, Ruhong,Kheirollah, Alireza,Yu, Chunjiang,Geng, Yong,Higgs, Henry N.,Chang, Ta-Yuan
experimental part, p. 9957 - 9963 (2011/08/06)
Acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) is a membrane-bound enzyme utilizing long-chain fatty acyl-coenzyme A and cholesterol to form cholesteryl esters and coenzyme A. Previously, we had expressed tagged human ACAT1 (hACAT1) in CHO cells and purified it to homogeneity; however, only a sparse amount of purified protein could be obtained. Here we report that the hACAT1 expression level in H293 cells is 18-fold higher than that in CHO cells. We have developed a milder purification procedure to purify the enzyme to homogeneity. The abundance of the purified protein enabled us to conduct difference intrinsic fluorescence spectroscopy to study the binding between the enzyme and its substrates in CHAPS/phospholipid mixed micelles. The results show that oleoyl-CoA binds to ACAT1 with Kd = 1.9 μM and elicits significant structural changes of the protein as manifested by the significantly positive changes in its fluorescence spectrum; stearoyl-CoA elicits a similar spectrum change but much lower in magnitude. Previously, kinetic studies had shown that cholesterol is an efficient substrate and an allosteric activator of ACAT1, while its diastereomer epicholesterol is neither a substrate nor an activator. Here we show that both cholesterol and epicholesterol induce positive changes in the ACAT1 fluorescence spectrum; however, the magnitude of spectrum changes induced by cholesterol is much larger than epicholesterol. These results show that stereospecificity, governed by the 3β-OH moiety in steroid ring A, plays an important role in the binding of cholesterol to ACAT1.
FeCl3·6H2O as a versatile catalyst for the esterification of steroid alcohols with fatty acids
Komura, Kenichi,Ozaki, Akiyoshi,Ieda, Noboru,Sugi, Yoshihiro
experimental part, p. 3407 - 3410 (2009/05/09)
FeCl3·6H2O is an active catalyst for the esterification of some steroid alcohols with fatty acids under azeotropic reflux in mesitylene as solvent. Georg Thieme Verlag Stuttgart.
Direct atom-efficient esterification between carboxylic acids and alcohols catalyzed by amphoteric, water-tolerant TiO(acac)2
Chen, Chien-Tien,Munot, Yogesh S.
, p. 8625 - 8627 (2007/10/03)
A diverse array of oxometallic species were examined as catalysts for a test direct condensation of benzoic acid and 2-phenylethanol in 1:1 stoichiometry. Besides group IVB MOCl2-XH2O and TiOX 2-xH2O, group VB VOCl2-xTHF and group IVB TiO(acac)2 were found to be the most efficient and water-tolerant catalysts for the test reaction. The new neutral catalytic protocol with the optimal TiO(acac)2 tolerates many stereo/electronic structural variations in both (di)-acid (1°-3° alkyl and aryl) and (di)alcohol (1°, 2° alkyl, and aryl) components with high chemoselectivity.
Fatty acid steryl, stanyl, and steroid esters by esterification and transesterification in vacuo using Candida rugosa lipase as catalyst
Weber, Nikolaus,Weitkamp, Petra,Mukherjee, Kumar D.
, p. 67 - 71 (2007/10/03)
Sterols (sitosterol; cholesterol, stigmasterol, ergosterol, and 7-dehydrocholesterol) and sitostanol have been converted in high to near-quantitative yields to the corresponding long-chain acyl esters via esterification with fatty acids or transesterification with methyl esters of fatty acids or triacylglycerols using lipase from Candida rugosa as biocatalyst in vacuo (20-40 mbar) at 40 °C. Neither organic solvent nor water is added in these reactions. Under similar conditions, cholesterol has been converted to cholesteryl butyrate and steroids (5aα-pregnan-3Bβ-ol-20-one or 5-pregnen-3β- ol-20-one) have been converted to their propionic acid esters, both in moderate to high yields, via transesterification with tributyrin and tripropionin, respectively. Reaction parameters studied in esterification include the temperature and the molar ratio of the substrates as well as the amount and reuse properties of the C. rugosa lipase. Lipases from porcine pancreas, Rhizopus arrhizus, and Chromobacterium viscosum are quite ineffective as biocatalysts for the esterification of cholesterol with oleic acid under the above conditions.
