596-94-1

Basic information

• Product Name: 20,22-dihydroxycholesterol
• Synonyms: 20,22-dihydroxycholesterol;(3β,22R)-Dihydroxy Cholesterol;Oxy-16;(20R,22R)-Dihydroxycholesterol;(22R)-5-Cholesten-3β,20α,22-triol;(22R)-Cholest-5-ene-3β,20,22-triol;(3β,22R)-Cholest-5-ene-3,20,22-triol;20α,22(R)-Dihydroxycholesterol
• CAS NO: 596-94-1
• Molecular Formula: C₂₇H₄₆O₃
• Molecular Weight: 418.65
• Product Categories: Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Steroids
• Mol File: 596-94-1.mol
• Article Data: 8

Chemical Properties

• Melting Point: 183 °C(Solv: ethyl acetate (141-78-6))
• Boiling Point: 553.5°Cat760mmHg
• Flash Point: 233.1°C
• Appearance: /
• Density: 1.08g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.55
• Solubility: ≤10mg/ml in ethanol;1.5mg/ml in DMSO;1.5mg/ml in dimethyl formamide
• PKA: 14.42±0.29(Predicted)
• CAS DataBase Reference: 20,22-dihydroxycholesterol(CAS DataBase Reference)
• NIST Chemistry Reference: 20,22-dihydroxycholesterol(596-94-1)
• EPA Substance Registry System: 20,22-dihydroxycholesterol(596-94-1)

Safety Data

• Hazardous Substances Data: 596-94-1(Hazardous Substances Data)

Usage

Description

Naturally occurring oxysterols are products of cholesterol oxidation that can stimulate the hedgehog (Hh) signaling pathway in target cells associated with cardiovascular disease and with bone formation. Depending on the target cell, activation of Hh signaling can modulate inflammatory responses to additional atherogenic factors such as lesion-producing macrophages or enable osteoblast differentiation. Oxy-16 is a synthetic oxysterol compound that may function as an antagonist of hedgehog activity. Published data regarding its efficacy remains forthcoming.

Definition

ChEBI: An oxysterol that is cholesterol substituted by hydroxy groups at positions 20 and 22 (the 20R,22R-stereoisomer).

in vitro

oxysterols have been shown to be associated with immunosuppression, apoptosis, atherosclerosis, inflammation, and cholesterol turnover. other studies aslo indicated that oxysterols were hedgehog (hh) signaling pathway activators and had potent osteoinductive properties. oxy-16, an oxysterol, was identified as a cell permeable oxygenated derivative of cholesterol that might be the end product or intermediate of the cholesterol excretion pathways. oxy-16 is currently used as a transport form for cholesterol across the blood brain barrier and membranes. the osteogenic differentiation caused by oxy-16 was cinsidered to be mediated via a wnt signaling-related, dkk-1-inhibitable mechanism [1].

references

[1] amantea, c. m.,kim, w.k.,meliton, v., et al. oxysterol-induced osteogenic differentiation of marrow stromal cells is regulated by dkk-1 inhibitable and pi3-kinase mediated signaling. journal of cellular biochemistry 105(2), 424-436 (2008).

InChI:InChI=1/C27H46O3/c1-17(2)6-11-24(29)27(5,30)23-10-9-21-20-8-7-18-16-19(28)12-14-25(18,3)22(20)13-15-26(21,23)4/h7,17,19-24,28-30H,6,8-16H2,1-5H3/t19-,20-,21-,22-,23-,24?,25-,26-,27+/m0/s1

Upstream product

• 1334232-72-2 C₂₈H₄₈O₃Si 
• 188955-65-9 3β-tert-butyldimethylsilyloxy-(20R)-20-hydroxy-pregna-5-en-dithiane 
• 57-88-5 cholesterol 
• 66007-51-0 (R)-1-((1aR,3aR,3bS,5aS,6S,8aS,8bS,10R,10aR)-10-Methoxy-3a,5a-dimethyl-hexadecahydro-cyclopenta[a]cyclopropa[2,3]cyclopenta[1,2-f]naphthalen-6-yl)-1-(R)-oxiranyl-ethanol 
• 79409-84-0 (3β,20S,22E,24S)-24-(phenylsulfinyl)-3-<(tetrahydro-2H-pyran-2-yl)oxy>cholesta-5,22-dien-20-ol 
• 79409-80-6 (3β,20S,22E)-24ξ-(phenylthio)-3-<(tetrahydro-2H-pyran-2-yl)oxy>-24ξ-(trimethylsilyl)cholesta-5,20-dien-20-ol 
• 79409-83-9 (3β,20S,22E,24S)-24-(phenylthio)-3-<(tetrahydro-2H-pyran-2-yl)oxy>cholesta-5,22-dien-20-ol 
• 79409-86-2 (3β,20R,22R,23E)-3-<(tetrahydro-2H-pyran-2-yl)oxy>cholesta-5,23-diene-20,22-diol 
• 79409-72-6 (Z)-(S)-2-[(3S,8S,9S,10R,13S,14S,17S)-10,13-Dimethyl-3-(tetrahydro-pyran-2-yloxy)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]-5-phenylsulfanyl-5-trimethylsilanyl-pent-4-en-2-ol 
• 54548-85-5 (20(22)E)-cholesta-5,20(22)-dien-3β-ol acetate 
• 782494-65-9 (20R,22R,23R)-22,23-epoxy-3β-(tert-butyldimethylsilyl)oxycholest-5-en-20-ol 
• 782494-64-8 (20R,22Z)-3β-(tert-butyldimethylsilyl)oxycholesta-5,22-dien-20-ol 
• 115910-64-0 (20R)-3β-(tert-butyldimethylsilyl)oxycholest-5-en-22-yn-20-ol 
• 58701-45-4 3β-t-butyldimethylsilyloxy-pregn-5-en-20-one 

Downstream Products

• 626-89-1 4-Methyl-1-pentanol 
• 145-13-1 Pregnenolone 
• 1119-16-0 isocaproic aldehyde 

Relevant articles and documents

Isotope-Labeling Studies Support the Electrophilic Compound i Iron Active Species, FeO3+, for the Carbon-Carbon Bond Cleavage Reaction of the Cholesterol Side-Chain Cleavage Enzyme, Cytochrome P450 11A1

The enzyme cytochrome P450 11A1 cleaves the C20-C22 carbon-carbon bond of cholesterol to form pregnenolone, the first 21-carbon precursor of all steroid hormones. Various reaction mechanisms are possible for the carbon-carbon bond cleavage step of P450 11A1, and most current proposals involve the oxoferryl active species, Compound I (FeO3+). Compound I can either (i) abstract an O-H hydrogen atom or (ii) be attacked by a nucleophilic hydroxy group of its substrate, 20R,22R-dihydroxycholesterol. The mechanism of this carbon-carbon bond cleavage step was tested using 18O-labeled molecular oxygen and purified P450 11A1. P450 11A1 was incubated with 20R,22R-dihydroxycholesterol in the presence of molecular oxygen (18O2), and coupled assays were used to trap the labile 18O atoms in the enzymatic products (i.e., isocaproaldehyde and pregnenolone). The resulting products were derivatized and the 18O content was analyzed by high-resolution mass spectrometry. P450 11A1 showed no incorporation of an 18O atom into either of its carbon-carbon bond cleavage products, pregnenolone and isocaproaldehyde. The positive control experiments established retention of the carbonyl oxygens in the enzymatic products during the trapping and derivatization processes. These results reveal a mechanism involving an electrophilic Compound I species that reacts with nucleophilic hydroxy groups in the 20R,22R-dihydroxycholesterol intermediate of the P450 11A1 reaction to produce the key steroid pregnenolone.

INHIBITION OF PPAR GAMMA EXPRESSION IN PREADIPOCYTE CELLS BY OXYSTEROLS

This invention relates, e.g., to methods and agents to inhibit peroxisome proliferator activated receptor expression (PPAR) in preadipocytes.

An improved synthesis of (20R,22R)-cholest-5-ene-3β,20,22-triol, an intermediate in steroid hormone formation and an activator of nuclear orphan receptor LXRα

Asymmetric dihydroxylation of (20(22)E)-cholesta-5,20(22)-dien-3β-ol acetate (2a), prepared from pregnenolone, gave a 1:1 mixture (67% yield) of (20R,22R)-cholest-5-ene-3β,20,22-triol 3-acetate (3a) and its 20S,22S isomer 3b. Highly purified 3a and 3b were obtained by semipreparative silver ion high performance liquid chromatography. Saponification of 3a and 3b gave (20R,22R)-cholest-5-ene-3β,20,22-triol (4a) and its 20S,22S isomer 4b. This simple approach provided the natural isomer 4a more efficiently than previously described chemical or enzymatic syntheses. Full 1H and 13C nuclear magnetic resonance data were presented for triols 4a and 4b and their synthetic precursors. Side-chain conformations of 2a, its 20(22)Z isomer, 4a, and 4b were studied by molecular mechanics and nuclear Overhauser effect difference spectroscopy.