Synthesis and crystal structure of 3β-p-bromobenzoyloxy-14α, 15α-epoxy-5α-cholest-7-ene

Conner, Benjamin N.; Parish, Edward J.; Schroepfer, George J.

doi:10.1016/0009-3084(77)90012-3

Cited by 18 publications

(6 citation statements)

References 15 publications

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“…X-ray crystallographic analysis has been employed to establish unequivocally the structures of oxygenated sterols (or their derivatives) shown to be potent regulators of sterol synthesis (112,337,485,665,707,767,800,922,927,1030,1031) or of key intermediates or by-products in the chemical syntheses of 15-oxygenated sterols of potential importance in biology or medicine (214,1195,1196). X-ray crystallographic analyses of the 25R-isomer of 26-OH-Chol (493,949) and its 25S-isomer (1146) have been presented.…”

Section: X-ray Crystal Structures Of Oxysterolsmentioning

confidence: 99%

“…A number of investigations have indicated that cyp7a activity can be modified in vitro by phosphorylation-dephosphorylation processes (209,214,256,347,397,530,709,893,903,1093). Other investigators (60,274,578) have not obtained results consistent with this potential in vitro modulation of cyp7a activity, perhaps due to differences in experimental conditions (709).…”

Section: B Formation Of 7-oxygenated Sterolsmentioning

confidence: 99%

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Oxysterols: Modulators of Cholesterol Metabolism and Other Processes

Schroepfer

2000

Physiological Reviews

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Oxygenated derivatives of cholesterol (oxysterols) present a remarkably diverse profile of biological activities, including effects on sphingolipid metabolism, platelet aggregation, apoptosis, and protein prenylation. The most notable oxysterol activities center around the regulation of cholesterol homeostasis, which appears to be controlled in part by a complex series of interactions of oxysterol ligands with various receptors, such as the oxysterol binding protein, the cellular nucleic acid binding protein, the sterol regulatory element binding protein, the LXR nuclear orphan receptors, and the low-density lipoprotein receptor. Identification of the endogenous oxysterol ligands and elucidation of their enzymatic origins are topics of active investigation. Except for 24, 25-epoxysterols, most oxysterols arise from cholesterol by autoxidation or by specific microsomal or mitochondrial oxidations, usually involving cytochrome P-450 species. Oxysterols are variously metabolized to esters, bile acids, steroid hormones, cholesterol, or other sterols through pathways that may differ according to the type of cell and mode of experimentation (in vitro, in vivo, cell culture). Reliable measurements of oxysterol levels and activities are hampered by low physiological concentrations (approximately 0.01-0.1 microM plasma) relative to cholesterol (approximately 5,000 microM) and by the susceptibility of cholesterol to autoxidation, which produces artifactual oxysterols that may also have potent activities. Reports describing the occurrence and levels of oxysterols in plasma, low-density lipoproteins, various tissues, and food products include many unrealistic data resulting from inattention to autoxidation and to limitations of the analytical methodology. Because of the widespread lack of appreciation for the technical difficulties involved in oxysterol research, a rigorous evaluation of the chromatographic and spectroscopic methods used in the isolation, characterization, and quantitation of oxysterols has been included. This review comprises a detailed and critical assessment of current knowledge regarding the formation, occurrence, metabolism, regulatory properties, and other activities of oxysterols in mammalian systems.

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Section: X-ray Crystal Structures Of Oxysterolsmentioning

confidence: 99%

Section: B Formation Of 7-oxygenated Sterolsmentioning

confidence: 99%

Oxysterols: Modulators of Cholesterol Metabolism and Other Processes

Schroepfer

2000

Physiological Reviews

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872

687

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“…A key precursor for the preparation of the desired compound was 3/3-benzoyloxy-14a,15a-epoxy-5a-cholest-7-ene which was obtained in 96% yield by treatment of pure 3/3-benzoyloxy-5«-cholesta-7,14-diene with zn-chloroperbenzoic acid.14 Unambiguous establishment of structure was based upon the results of X-ray crystallographic analysis of 3/3-p-bromobenzoyloxy-14a,15a-epoxy-5a-cholest-7-ene. 15 Treatment of 3/3-benzoyloxy-14a,15a-epoxy-5a-cholest-7-ene with refluxing ethanolic KOH gave, in 53% yield, 5a-cholest-8( 14)-ene-3f3,7£,lo|-triol which was characterized by infrared, NMR, and mass spectroscopy and by conversion to 5a-cholest-8( 14)-ene-3,7,15-trione. The A8(14)-3/3,7£,15|-triol was found to be a potent inhibitor of sterol synthesis.12 Apart from the high activity of this compound in the inhibition of sterol biosynthesis, the triol is of considerable interest since we have now found that 5a-cholest-8( 14)-ene-3/3,7|,15£-triol, upon treatment with hydrochloric acid in ethanol, gives 5acholest-8( 14)-en-3/3-ol-15-one in high (87%) yield.…”

mentioning

confidence: 99%

Carbon-13 nuclear magnetic resonance studies of allylic hydroxysterols. Assignment of structure of 5.alpha.-cholest-8(14)-ene-3.beta.,7.alpha.,15.alpha.-triol, an inhibitor of sterol synthesis

Tsuda¹,

Parish²,

Schroepfer³

1979

J. Org. Chem.

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“…3/?-p-bromobenzoyloxycholest-8(14)-en-15/?-ol (Phillips et ah, 1976), 3jS-p-bromobenzoyloxy-14a,15a-epoxycholest-7-ene (Conner et al, 1977), 14jS-cholest-7-ene-3j?,15j?-diol-p-bromobenzoate (Gilliland et al, 1977), 3j8-/?-bromobenzoyloxy-14a-methylcholest-7-en-15j?-ol (Spike et al, 1978), 14a-ethylcholest-7-ene-3/?,15a-diol di-p-bromobenzoate (Monger et al, 1980), and 3j8-^-bromobenzoyloxy-15j9-methyl-14jS-cholest-7-ene-15a-ol Bowen et al, 1988). …”

Section: E X-ray Crystallographymentioning

confidence: 99%