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

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

Uses

Used in Pharmaceutical Industry:
20,22-Dihydroxycholesterol is used as a pharmaceutical agent for its potential role in modulating the hedgehog (Hh) signaling pathway. This pathway is involved in various biological processes, including cardiovascular disease and bone formation. By targeting this pathway, 20,22-dihydroxycholesterol may offer therapeutic benefits in treating related conditions.
Used in Research Applications:
In the field of research, 20,22-dihydroxycholesterol is used as a tool to study the hedgehog (Hh) signaling pathway and its role in cellular processes. This oxysterol can help researchers understand the mechanisms underlying cardiovascular disease and bone formation, potentially leading to the development of new therapeutic strategies.
Used in Drug Development:
20,22-Dihydroxycholesterol may be utilized in the development of new drugs targeting the hedgehog (Hh) signaling pathway. As an antagonist of hedgehog activity, it could potentially be used to treat conditions related to the dysregulation of this pathway, such as certain cancers or developmental disorders.

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

• 79409-87-3 (3β,20R,22R)-3-<(tetrahydro-2H-pyran-2-yl)oxy>cholesta-5-ene-20,22-diol 
• 4548-78-1 (3-methylbutyl)magnesium bromide 
• 66007-54-3 (20R)-20,3β-dihydroxypregna-5-ene-22-aldehyde 
• 107-82-4 i-pentyl bromide 
• 60084-24-4 (20R,22R)-cholest-5-ene-3β,20,22-triol 3-acetate 
• 7154-75-8 4-methylpentyne 
• 145-13-1 Pregnenolone 
• 58701-45-4 3β-t-butyldimethylsilyloxy-pregn-5-en-20-one 
• 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 
• 79409-86-2 (3β,20R,22R,23E)-3-<(tetrahydro-2H-pyran-2-yl)oxy>cholesta-5,23-diene-20,22-diol 
• 79409-83-9 (3β,20S,22E,24S)-24-(phenylthio)-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 
• 79409-84-0 (3β,20S,22E,24S)-24-(phenylsulfinyl)-3-<(tetrahydro-2H-pyran-2-yl)oxy>cholesta-5,22-dien-20-ol 
• 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 

Downstream Products

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

Relevant articles and documents

OXYSTEROLS THAT ACTIVATE LIVER X RECEPTOR SIGNALING AND INHIBIT HEDGEHOG SIGNALING

This invention relates, e.g., to compositions comprising oxysterol compounds represented by Formula I or Formula II, e.g., comprising one or more of Oxy 16, Oxy 22, Oxy30, Oxy 31, Oxy35, Oxy37, Oxy43, Oxy44, Oxy45 or Oxy47. The compounds are shown to be Hedgehog pathway inhibiting, and to act as agonists for liver X receptor (LXR). Also disclosed are methods of using compositions of the invention to inhibit Hedgehog signaling effects, such as cell proliferation, including treating subjects in need thereof, and pharmaceutical compositions and kits for implementing methods of the invention.

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.

Stereoselective synthesis of (22R)- and (22S)-castasterone/ponasterone a hybrid compounds and evaluation of their molting hormone activity

Two stereoisomers of a castasterone/ponasterone A hybrid compound, the (20R,22R) and (20R,22S)-isomers of 2α,3α,20,22-tetrahydroxy- 5α-cholestan-6-one, were synthesized stereoselectively and their binding activity to the ecdysteroid receptor was determined. From the concentration-response curve for the inhibition of the incorporation of tritiated ponasterone A into ecdysteroid receptor containing insect cells, the concentration (IC50) required to inhibit 50% of the incorporation of radioactivity into cells was evaluated. The IC50 values of the (22R)- and (22S)-isomers were determined to be 0.30 and 38.9 μM against Kc cells, respectively, indicating that the (22R)-isomer is about 100 times more potent than the corresponding (22S)-isomer. IC50 values of these compounds against lepidopteran Sf-9 cells were determined to be 0.36 and 12.9 μM, respectively. The molting hormonal effect was examined in a Chilo suppressalis integument system and the 50% effective concentration for the stimulation of N-acetylglucosamine incorporation into the cultured integument was determined to be 2.7 μM for the (22R)-isomer, while the (22S)-isomer was inactive. On the other hand, both isomers did not show brassinolide-like activity in the rice lamina inclination assay.

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.