Selective Oxidation with N-Bromosuccinimide. II. Cholestane-3β,5α,6β-triol

Fieser, Louis; Rajagopalan, S.

doi:10.1021/ja01180a016

Cited by 179 publications

(36 citation statements)

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“…All data were consistent with the unknown metabolite as cholestan-6-oxo-3,5-diol. This compound was synthesized (25) and was found to have the same retention time and electron ionization mass spectrum as the unknown metabolite (Fig. 5B).…”

Section: Fig 3 Formation Of 5␤6␤-cholesterol Epoxide In 16-hbe Celmentioning

confidence: 96%

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Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant

Pulfer

Murphy

2004

Journal of Biological Chemistry

105

102

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Exposure of the lung to concentrations of ozone found in ambient air is known to cause toxicity to the epithelial cells of the lung. Because of the chemical reactivity of ozone, it likely reacts with target molecules in pulmonary surfactant, a lipid-rich material that lines the epithelial cells in the airways. Phospholipids containing unsaturated fatty acyl groups and cholesterol would be susceptible to attack by ozone, which may lead to the formation of cytotoxic products. Whereas free radicalderived oxidized cholesterol products have been frequently studied for their cytotoxic effects, ozonized cholesterol products have not been studied, although they could reasonably play a role in the toxicity of ozone. The reaction of ozone with cholesterol yielded a complex series of products including 3␤-hydroxy-5-oxo-5,6-secocholestan-6-al, 5-hydroperoxy-B-homo-6-oxa-cholestan-3␤,7a-diol, and 5␤,6␤-epoxycholesterol. Mass spectrometry and radioactive monitoring were used to identify the major cholesterol-derived product during the reaction of 2 ppm ozone in surfactant as 5␤,6␤-epoxycholesterol, which is only a minor product during ozonolysis of cholesterol in solution. A dose-dependent formation of 5␤,6␤-epoxycholesterol was also seen during direct exposure of intact cultured human bronchial epithelial cells (16-HBE) to ozone. Studies of the metabolism of this epoxide in lung epithelial cells yielded small amounts of the expected metabolite, cholestan-3␤,5␣,6␤-triol, and more abundant levels of an unexpected metabolite, cholestan-6-oxo-3␤,5␣-diol. Both 5␤,6␤-epoxycholesterol and cholestan-6-oxo-3␤,5␣-diol were shown to be cytotoxic to cultured 16-HBE cells. A possible mechanism for cytotoxicity is the ability of these oxysterols to inhibit isoprenoid-based cholesterol biosynthesis in these cells.Human exposure to 0.2 ppm levels of ozone in ambient air has been shown to cause numerous pulmonary effects such as increased airway inflammation and decreased pulmonary function (1, 2). Studies of ozone in animals using up to 3 ppm ozone have been shown to cause increased airway hyperresponsiveness and epithelial cell death. It has been hypothesized that the very high chemical reactivity of ozone limits the distribution of this gas in the pulmonary system, preventing direct exposure to the cellular components of the lung. In part ozone may react with the various components of the epithelial cell lining fluid in the lung, also known as pulmonary surfactant, which includes proteins, lipids, and single electron antioxidant agents such as ascorbic acid (3-5). Because of the very high reactivity of ozone with lipids containing double bonds, considerable emphasis has been placed on the reaction of ozone with lipid compounds in the lungs and the possibility that the adverse effects of ozone are mediated by lipid-ozonized products (6). Evidence in support of this theory has been accumulating with the identification of biologically active phospholipids (7) such as 1-hexadecanoyl-2-(9-oxo-nonanoyl)-glycerophosphocholine, found following oz...

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Section: Fig 3 Formation Of 5␤6␤-cholesterol Epoxide In 16-hbe Celmentioning

confidence: 96%

“…The 3,5,6-triol was purified by RP-HPLC as described above for ␤-epoxide. Cholestan-6-oxo-3,5-diol (6-oxo-3,5-diol) was synthesized by the method of Fieser and Rajagopalan (25). Briefly, 10 mg of cholestanetriol was dissolved in 4.5 ml of ether, 750 l of methanol, and 750 l of water.…”

Section: Formation Of Active Oxysterols During Cholesterol Ozonolysismentioning

confidence: 99%

Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant

Pulfer

Murphy

2004

Journal of Biological Chemistry

105

102

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“…Purification of cholestanol by oxidation. The cholestanol-containing fraction from TLC system 3 in Patient 8 was also treated with formic acid and hydrogen peroxide after addition of 50 mg cholestanol as carrier (18). The product was partitioned between petroleum ether and methanol and the cholestanol was oxidized with perbenzoic acid and chromatographed as described (19).…”

Section: Methodsmentioning

confidence: 99%

Sterol synthesis in the human arterial intima

Chobanian¹

1968

J. Clin. Invest.

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“…3P,5-Dihydroxy-5a-androstane-6,17-dione (9b) This was prepared by a modification of the method of Fieser and Rajagopalan (30). 3J3,5,6P-Trihydroxy-5a-androstan-17-one (3.2 g) was dissolved in a mixture of dioxan (50 mL) and water (5 mL).…”

Section: Preparation Of Substratesmentioning

confidence: 99%

Microbial hydroxylation of steroids. 5. Metabolism of androst-5-ene-3,17-dione and related compounds by Rhizopusarrhizus ATCC 11145

Holland¹,

Diakow²

1979

Can. J. Chem.

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The products of the incubation of androst-5-ene-3,17-dione @a), 3B-hydroxyandrost-5-ene-17-one (2b), and androsta-3,s-diene-17-one ( The C-6P hydroxylation of androst-4-ene-3,17-dione (la) by R. arrhizus ATCC 11 145 proceeds via the A395-enol form of the ketone (1). In an attempt to gain further insight into this enzymic process, we have studied the metabolism of androst-5-ene-3,17-dione (2a), the corresponding 3P-alcohol (2b), and the A3.5-enol analogue 3, by R. arrhizus under a variety of conditions. In addition we have incubated a series of epoxy steroids and related compounds, 4-9.

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Selective Oxidation with N-Bromosuccinimide. II. Cholestane-3β,5α,6β-triol

Cited by 179 publications

References 0 publications

Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant

Formation of Biologically Active Oxysterols during Ozonolysis of Cholesterol Present in Lung Surfactant

Sterol synthesis in the human arterial intima

Microbial hydroxylation of steroids. 5. Metabolism of androst-5-ene-3,17-dione and related compounds by Rhizopusarrhizus ATCC 11145

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