17320-10-4

Usage

Uses

Used in Pharmaceutical Industry:
4-BETA-HYDROXYCHOLESTEROL is used as a potential ligand for the nuclear receptor LXR, playing a crucial role in the regulation of cellular processes and gene expression. Its interaction with LXR can have implications in the development of therapeutic strategies for various diseases.
Used in Drug Metabolism Research:
As a new endogenous CYP3A marker, 4-BETA-HYDROXYCHOLESTEROL is used in the study of drug metabolism, particularly in understanding the role of cytochrome P450 3A4 enzyme in the metabolism of various drugs and compounds. This can help in the development of more effective and safer medications.
Used in Chemical and Analytical Research:
4-BETA-HYDROXYCHOLESTEROL, being a white solid with distinct chemical properties, is used as a research compound in chemical and analytical studies. Its unique structure and properties make it a valuable tool for investigating various chemical reactions and processes.
Used in Cholesterol Metabolism Studies:
As a metabolite of cholesterol, 4-BETA-HYDROXYCHOLESTEROL is used in research to understand the complex pathways and mechanisms involved in cholesterol metabolism. This knowledge can contribute to the development of treatments for conditions related to cholesterol imbalance, such as atherosclerosis and hypercholesterolemia.

Biological Activity

4β-hydroxy cholesterol is an endogenous marker for cyp3a4/5 activity [1].cytochome p450 3a4 (cyp3a4) and cyp3a5 are important drug-metabolizing enzymes that oxidize small foreign organic molecules, such as toxins or drugs, and remove them from the body. they exhibit a large variation in hepatic expression and biological activity between different individuals. patients treated with drugs known to be strong inducers of cyp3a4/5 have highly elevated levels of 4β-hydroxycholesterol in the circulation [1].4β-hydroxy cholesterol, an endogenous oxysterol found in human circulation, is formed from cholesterol by cytochrome p450 (cyp) 3a4 and cyp3a5. in 12 different occasions during a 3-month period, the cvs for 4β-hydroxycholesterol ranged from 4.8 to 13.2% with an average cv of 7.1% at an average concentration of 30.8 ng/ml. in 24 volunteers treated with rifampicin, a strong cyp3a4/5 inducer, 4β-hydroxycholesterol increased in a dose-dependent way, while the isomer 4α-hydroycholesterol was not influenced by rifampicin treatment. these results suggested that 4β-hydroxy cholesterol is an endogenous marker for cyp3a4/5 activity [1].

references

[1]. diczfalusy u, kanebratt kp, bredberg e, et al. 4beta-hydroxycholesterol as an endogenous marker for cyp3a4/5 activity. stability and half-life of elimination after induction with rifampicin. br j clin pharmacol. 2009 jan;67(1):38-43.

InChI:InChI=1/C27H46O2/c1-17(2)7-6-8-18(3)20-11-12-21-19-9-10-23-25(29)24(28)14-16-27(23,5)22(19)13-15-26(20,21)4/h10,17-22,24-25,28-29H,6-9,11-16H2,1-5H3

Upstream product

• 20230-31-3 (4,5)α-epoxy-5α-cholestan-3β-ol 
• 50611-92-2 3β-benzoyloxycholest-5-ene-4-one 
• 51238-16-5 3β-acetoxy-4β-hydroxy-5-cholestene 
• 604-35-3 Cholesteryl acetate 
• 57-88-5 cholesterol 
• 57-88-5 cholesterol 
• 2309-27-5 3β-hydroxy-6β-nitrocholest-4-ene 
• 1857-80-3 5α,6β-dibromocholestan-3β-ol 
• 5034-92-4 5β,6α-dibromocholestanol 
• 7446-08-4 selenium(IV) oxide 
• 7732-18-5 water 
• 64-19-7 acetic acid 
• 71-43-2 benzene 
• 110-86-1 pyridine 

Downstream Products

• 601-57-0 Cholest-4-en-3-one 
• 481-21-0 cholestane 
• 481-20-9 5β-cholestane 
• 80-97-7 Cholestanol 
• 54339-68-3 4-cholestene-3,6-dione 
• 2243-09-6 5α-cholestane-3,6-dione 
• 56533-66-5 3β-acetoxycholest-5-en-4-one 
• 5847-14-3 3β-(toluene-4-sulfonyloxy)-cholest-5-en-4β-ol 

Relevant academic research and scientific papers

H-Atom Abstraction vs Addition: Accounting for the Diverse Product Distribution in the Autoxidation of Cholesterol and Its Esters

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.

Cholesterol transformations during heat treatment

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.

Improved synthesis and in vitro evaluation of the cytotoxic profile of oxysterols oxidized at C4 (4α- and 4β-hydroxycholesterol) and C7 (7-ketocholesterol, 7α- and 7β-hydroxycholesterol) on cells of the central nervous system

Whereas the biological activities of oxysterols oxidized at C7 (7-ketocholesterol (7KC), 7β-hydroxycholesterol (7β-OHC), 7α-hydroxycholesterol (7α-OHC)) are well documented, those of oxysterols oxidized at C4 (4β-hydroxycholesterol (4β-OHC), 4α-hydroxycholesterol (4α-OHC)) are not well known, especially on the cells of the central nervous system. Therefore, an improved methodology has been validated for 4β-OHC and 4α-OHC synthesis, and the effects on cell viability and cell growth of these molecules were studied on immortalized, tumoral and normal brain cells (158N, C6 and SK-N-BE cells, and mixed primary cultures of astrocytes and oligodendrocytes). Whereas inhibition of cell growth with 7KC, 7β-OHC, and 7α-OHC is associated with a decrease of cell viability (cytotoxic activities), our data establish that 4β-OHC and 4α-OHC have no effect on cell viability, and no or minor effect on cell growth evocating cytostatic properties. Thus, comparatively to oxysterols oxidized at C7, the toxicity of oxysterols oxidized at C4 is in the following range of order: 7KC ≥ 7β-OHC > 7α-OHC > (4β-OHC ≥ 4α-OHC). Interestingly, to date, 4β-OHC and 4α-OHC are the only oxysterols identified with cytostatic properties suggesting that these molecules, whereas not cytotoxic, may have some interests to counteract cell proliferation.

Oxidation with selenium dioxide: The first report of solvent-selective steroidal aromatization, efficient access to 4β,7α-dihydroxy steroids, and syntheses of natural diaromatic ergosterols

Selenium dioxide oxidation of cholesterol reveals a solvent-dependent product selectivity and facile one-pot synthesis of three derivatives, including aromatic analogues of naturally occurring ergosterol. Efficient access to 4β,7α-dihydroxy cholesterol is

Synthesis of [D4]- and [D7]-4β- hydroxycholesterols for use in a novel drug-drug interaction assay

Cytochrome P450 3A (CYP3A) enzymes are involved in the metabolism of over half of today's prescription drugs. As a result, drugs metabolized by CYP3A have a risk of drug-drug interactions (DDIs). Recent studies have shown the potential to use 4β-hydroxych

Highly efficient epoxidation of unsaturated steroids using magnesium bis(monoperoxyphthalate) hexahydrate

Fast generation of epoxides from the corresponding homoallylic and allylic steroidal olefins was developed by using magnesium bis(monoperoxyphthalate) hexahydrate (MMPP) as oxidant suspended in acetonitrile (CH3CN) at reflux temperature. The protocol involves the use of a safe readily available oxidant along with an easy work-up, which renders the process very efficient. Selective 4,5- and 5,6-epoxidations of steroids are reported. Among them, highly stereoselective epoxidation of Δ5-B-nor-cholestanes was achieved. Moreover, the method is chemoselective for the 5,6-position and can be applied to the epoxidation of ring-A enones.

Efficient chemoenzymatic synthesis, cytotoxic evaluation, and SAR of epoxysterols

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 and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents

Taking into account the structural requirements for cytotoxicity, several new hydroximinosteroid derivatives have been prepared and evaluated for their cytotoxic activity against A-549, H116, PSN1, and T98G cultured tumor cell lines in order to obtain further information on the potential pharmacophoric core of this type of compound. The influence of the oxygenated position in the A ring, the presence of an additional oxygenated position at C-7 and C-16, and a fluorinated position at C-5 were considered in order to study the structure-activity relationships. The results reveal the importance of oxygenated positions in the A ring (e.g., 4,5-epoxide showed an IC50 value against HCT-116 under micromolar level) for an increase in cytotoxic activity in this type of compound. Furthermore, they showed an important selectivity toward colon tumor line (HCT-116).

Sterol synthesis. Preparation and characterization of fluorinated and deuterated analogs of oxygenated derivatives of cholesterol

Oxygenated sterols, including both autoxidation products and sterol metabolites, have many important biological activities. Identification and quantitation of oxysterols by chromatographic and spectroscopic methods is greatly facilitated by the availability of authentic standards, and deuterated and fluorinated analogs are valuable as internal standards for quantitation. We describe the preparation, purification and characterization of 43 oxygenated sterols, including the 4β-hydroxy, 7α-hydroxy, 7β-hydroxy, 7-keto, and 19-hydroxy derivatives of cholesterol and their analogs with 25,26,26,26,27,27,27-heptafluoro (F7) and 26,26,26,27,27,27-hexadeuterio (d6) substitution. The 7α-hydroxy, 7β-hydroxy, and 7-keto derivatives of (25R)-cholest-5-ene-3β,26-diol (1d) and their 16,16-dideuterio analogs were also prepared. These d2-26-hydroxysterols and [16,16-2H2]-(25R)-cholest-5-ene-3β,26-diol (1e) were synthesized from [16,16-2H2]-(25R)-cholest-5-ene-3β,26-diol diacetate (2e), which can be prepared from diosgenin. The highly specific deuterium incorporation at C-16 in 1e and 2e should be useful in mass spectral analysis of 26-hydroxycholesterol samples by isotope dilution methods. The Δ5-3β,7α,26- and Δ5-3β,7β,26-triols were regioselectively oxidized/isomerized to the corresponding Δ4-3-ketosteroids with cholesterol oxidase. Also described are 5,6α-epoxy-5α-cholestan-3β-ol, its 5β,6β-isomer, cholestane-3β,5α,6β-triol, their F7 and d6 derivatives, and d3-25-hydroxycholesterol, which was prepared from 3β-acetoxy-27-norcholest-5-en-25-one (30). The 43 oxysterols and most synthetic intermediates were isolated in high purity and characterized by chromatographic and spectroscopic methods, including mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy. Detailed mass spectral assignments are presented, and 1H NMR stereochemical assignments are derived for the C-19 protons of 19-hydroxysterols and for the side chain protons of 30. Copyright (C) 1999 Elsevier Science Ireland Ltd.

A novel allylic oxidation using a combination of formic acid and selenium dioxide

A combination of formic acid and selenium dioxide in dioxane has been found to be an efficient system for the allylic oxygenation of olefins, in particular for sterically hindered ones, leading to the corresponding allylic alcohols or formates.