55700-78-2Relevant academic research and scientific papers
H-Atom Abstraction vs Addition: Accounting for the Diverse Product Distribution in the Autoxidation of Cholesterol and Its Esters
Zielinski, Zosia A. M.,Pratt, Derek A.
, p. 3037 - 3051 (2019/02/19)
We recently communicated that the free-radical-mediated oxidation (autoxidation) of cholesterol yields a more complex mixture of hydroperoxide products than previously appreciated. In addition to the epimers of the major product, cholesterol 7-hydroperoxide, the epimers of each of the regioisomeric 4- and 6-hydroperoxides are formed as is the 5α-hydroperoxide in the presence of a good H-atom donor. Herein, we complete the story by reporting the products resulting from competing peroxyl radical addition to cholesterol, the stereoisomeric cholesterol-5,6-epoxides, which account for 12% of the oxidation products, as well as electrophilic dehydration products of the cholesterol hydroperoxides, 4-, 6-, and 7-ketocholesterol. Moreover, we interrogate how their distribution - and abundance relative to the H-atom abstraction products - changes in the presence of good H-atom donors, which has serious implications for how these oxysterols are used as biomarkers. The resolution and quantification of all autoxidation products by LC-MS/MS was greatly enabled by the synthesis of a new isotopically labeled cholesterol standard and corresponding selected autoxidation products. The autoxidation of cholesteryl acetate was also investigated as a model for the cholesterol esters which abound in vivo. Although esterification of cholesterol imparts measurable stereoelectronic effects, most importantly reflected in the fact that it autoxidizes at 4 times the rate of unesterified cholesterol, the product distribution is largely similar to that of cholesterol. Deuteration of the allylic positions in cholesterol suppresses autoxidation by H-atom transfer (HAT) in favor of addition, such that the epoxides are the major products. The corresponding kinetic isotope effect (kH/kD ～ 20) indicates that tunneling underlies the preference for the HAT pathway.
Ring opening of epoxides with [18F]FeF species to produce [18F]fluorohydrin PET imaging agents
Verhoog, Stefan,Brooks, Allen F.,Winton, Wade P.,Viglianti, Benjamin L.,Sanford, Melanie S.,Scott, Peter J.H.
supporting information, p. 6361 - 6364 (2019/06/07)
A simple technique for the preparation of [18F]HF has been developed and applied to the generation of an [18F]FeF species for opening sterically hindered epoxides. This method has been successfully employed to prepare four drug-like molecules, including 5-[18F]fluoro-6-hydroxy-cholesterol, a potential adrenal/endocrine PET imaging agent. This easily automated one-pot procedure produces sterically hindered fluorohydrin PET imaging agents in good yields and high molar activities.
Chemoselective epoxidation of cholesterol derivatives on a surface-designed molecularly imprinted Ru-porphyrin catalyst
Muratsugu, Satoshi,Baba, Hiroshi,Tanimoto, Tatsuya,Sawaguchi, Kana,Ikemoto, Satoru,Tasaki, Masahiro,Terao, Yosuke,Tada, Mizuki
supporting information, p. 5114 - 5117 (2018/05/26)
A new molecularly imprinted Ru-porphyrin complex catalyst on a SiO2 support was designed, prepared, and characterized in a step-by-step manner for the C5C6 epoxidation of cholesterol derivatives. High chemoselectivity for the C5C6 epoxidation of cholesterol derivatives without protecting the 3-position OH group and other oxidizable functional groups was achieved on the molecularly imprinted catalyst.
Solvent-free synthesis of 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol as potential antiproliferative agents
Soto-Castro, Delia,Lara Contreras, Roberto Carlos,Pina-Canseco, María,Santillán, Rosa,Hernández-Huerta, María Teresa,Negrón Silva, Guillermo E.,Pérez-Campos, Eduardo,Rincón, Susana
supporting information, p. 92 - 100 (2017/09/19)
In this paper is described a synthetic route to 6β-phenylamino-cholestan-3β,5α-diol and (25R)-6β-phenylaminospirostan-3β,5α-diol, starting from cholesterol and diosgenin, respectively. The products were obtained in two steps by epoxidation followed by aminolysis, through an environmentally friendly and solvent-free method mediated by SZ (sulfated zirconia) as catalyst. The use of SZ allows chemo- and regioselective ring opening of the 5,6α-epoxide during the aminolysis reaction eliminating the required separation of the epoxide mixture. The products obtained were spectroscopically characterized by 1H, PENDANT 13C NMR and HETCOR experiments, and complemented with FTIR-ATR and HRMS. The antiproliferative effect of the β-aminoalcohols was evaluated on MCF-7 cells after 48 h of incubation, by MTT and CVS assays. These methodologies showed that both compounds have antiproliferative activity, being more active the cholesterol analogue. Additionally, the cell images obtained by Harris’ Hematoxylin and Eosin (H&E) staining protocol, evidenced formation of apoptotic bodies due to the presence of the obtained β-aminoalcohols in a dose-dependent manner.
Effect of Eleven Antioxidants in Inhibiting Thermal Oxidation of Cholesterol
Xu, Guihua,Liu, Donghong,Zhao, Gongling,Chen, Shiguo,Wang, Jun,Ye, Xingqian
, p. 215 - 225 (2016/02/03)
Eleven antioxidants including nine phenolic compounds (rutin, quercetin, hesperidin, hesperetin, naringin, naringenin, chlorogenic acid, caffeic acid, ferulic acid), vitamin E (α-tocopherol), and butylated hydroxytoluene (BHT) were selected to investigate their inhibitory effects on thermal oxidation of cholesterol in air and lard. The results indicated that the unoxidized cholesterol decreased with heating time whilst cholesterol oxidation products (COPs) increased with heating time. The major COPs produced were 7α-hydroxycholesterol, 7β-hydroxycholesterol, 5,6β-epoxycholesterol, 5,6α-epoxycholesterol, and 7-ketocholesterol. When cholesterol was heated in air for an hour, rutin, quercetin, chlorogenic acid, and caffeic acid showed a strong inhibitory effect. When cholesterol was heated in lard, caffeic acid, quercetin, and chlorogenic acid demonstrated inhibitory action during the initial 0.5 h (p a high flame is recommended. If baking or deep fat frying food in oil, it is best to limit cooking time to within 0.5 h.
Cholesterol transformations during heat treatment
Derewiaka,Molińska
, p. 233 - 240 (2015/01/09)
The aim of the study was to characterise products of cholesterol standard changes during thermal processing. Cholesterol was heated at 120 °C, 150 °C, 180 °C and 220 °C from 30 to 180 min. The highest losses of cholesterol content were found during thermal processing at 220 °C, whereas the highest content of cholesterol oxidation products was observed at temperature of 150 °C. The production of volatile compounds was stimulated by the increase of temperature. Treatment of cholesterol at higher temperatures i.e. 180 °C and 220 °C led to the formation of polymers and other products e.g. cholestadienes and fragmented cholesterol molecules. Further studies are required to identify the structure of cholesterol oligomers and to establish volatile compounds, which are markers of cholesterol transformations, mainly oxidation.
Biosynthesis of 20-hydroxyecdysone in plants: 3β-Hydroxy-5β-cholestan-6-one as an intermediate immediately after cholesterol in Ajuga hairy roots
Fujimoto, Yoshinori,Maeda, Izumi,Ohyama, Kiyoshi,Hikiba, Juri,Kataoka, Hiroshi
, p. 59 - 64 (2015/02/19)
3β-Hydroxy-5β-cholestan-6-one was identified in the EtOAc extract of Ajuga hairy roots by micro-analysis using LC-MS/MS in the multiple reaction mode (MRM). Furthermore, administration of (2,2,4,4,7,7-2H6)- and (2,2,4,4,6,7,7-2H7)-cholesterols to the hairy roots followed by LC-MS/MS analysis of the EtOAc extract of the hairy roots indicated that cholesterol was converted to the 5β-ketone with hydrogen migration from the C-6 to the C-5 position. These findings, in conjunction with the previous observation that the ketone was efficiently converted to 20-hydroxyecdysone, strongly suggest that the 5β-ketone is an intermediate immediately formed after cholesterol during 20-hydroxyecdysone biosynthesis in Ajuga sp. In addition, the mechanism of the 5β-ketone formation from cholesterol is discussed.
Efficient trans-diaxial hydroxylation of Δ5-steroids
Carvalho, Jo?o F.S.,Silva, M. Manuel Cruz,Sá e Melo, M. Luisa
scheme or table, p. 2455 - 2462 (2010/06/14)
A convenient, fast, and high-yielding process to synthesize 5α,6β-dihydroxysteroids directly from the correspondent Δ5-steroids is reported. The reaction protocol consists in the conjugation of a readily available and stable oxidant, magnesium bis(monoperoxyphthalate) hexahydrate, with the non-toxic bismuth(III) triflate in acetone to afford the trans-diaxial hydroxylation product in a stepwise manner and in excellent yields.
Efficient chemoenzymatic synthesis, cytotoxic evaluation, and SAR of epoxysterols
Carvalho, Jo?o F. S.,Cruz Silva, M. Manuel,Moreira, Jo?o N.,Sim?es, Sérgio,Sá E Melo, M. Luisa
experimental part, p. 4007 - 4019 (2009/12/26)
A library of diastereomerically pure epoxysterols, prepared by combining chemical and enzymatic methodologies, was evaluated for cytotoxicity toward human cancer and noncancer cell lines. Unsaturated steroids were oxidized by magnesium bis(monoperoxyphthalate) hexahydrate in acetonitrile, and the resulting epimeric epoxides were enzymatically separated using Novozym 435 or lipase AY. Some of the synthesized epoxysterols have potent cytotoxicity and higher activity on cancer cell lines HT29 and LAMA-84.
Synthesis of new alkylaminooxysterols with potent cell differentiating activities: Identification of leads for the treatment of cancer and neurodegenerative diseases
De Medina, Philippe,Paillasse, Michael R.,Payre, Bruno,Silvente-Poirot, Sandrine,Poirot, Marc
experimental part, p. 7765 - 7777 (2010/08/03)
We describe here the syntheses and the biological properties of new alkylaminooxysterols. Compounds were synthesized through the trans-diaxial aminolysis of 5,6-α-epoxysterols with various natural amines including histamine, putrescine, spermidine, or spermine. The regioselective synthesis of these 16 new 5α-hydroxyl-6β-aminoalkylsterols is presented. Compounds were first screened for dendrite outgrowth and cytotoxicity in vitro, and two leads were selected and further characterized. 5α-Hydroxy-6β-[2- (1Himidazol-4-yl)ethylamino]cholestan-3β-ol, called dendrogenin A, induced growth control, differentiation, and the death of tumor cell lines representative of various cancers including metastatic melanoma and breast cancer. 5α-Hydroxy-6β-[3-(4-aminobutylamino)propylamino]cholest-7-en- 3β-ol, called dendrogenin B, induced neurite outgrowth on various cell lines, neuronal differentiation in pluripotent cells, and survival of normal neurones at nanomolar concentrations. In summary, we report that two new alkylaminooxysterols, dendrogenin A and dendrogenin B, are the first members of a class of compounds that induce cell differentiation at nanomolar concentrations and represent promising new leads for the treatment of cancer or neurodegenerative diseases.
