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Query: CAS:22373-09-7 (cholestane)
 779 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A side-chain fluorinated delta 8(14)-15-ketosterol has been synthesized from 3 beta-acetoxy-24-hydroxy-5 alpha-chol-8(14)-en-15-one (VII) as part of a program to prepare new analogs of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I), a potent regulator of cholesterol metabolism. 3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one (VIII) was prepared in five steps from VII in 38% overall yield. Dehydration of VII via the ortho-nitrophenylselenide to the 23-ene, followed by addition of (CF3)2CFI gave 3 beta-acetoxy-23R-iodo-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one. Reductive deiodination with tributyltin hydride, followed by hydrolysis of the acetate gave VIII. 25,26,26,26,27,27,27-Heptafluorocholest-5-en-3 beta-ol (XXI) was prepared in eight steps in 31% overall yield from 3 alpha,6 alpha-diacetoxy-5 beta-cholanic acid (XIII). Compound XIII was reduced with borane-methyl sulfide to the corresponding 24-hydroxysteroid, which was converted to 3 alpha,6 alpha-diacetoxy-25,26,26,26,27,27,27-heptafluoro-5 beta-cholestane (XVIII) by reactions analogous to those developed for the preparation of VIII from VII. Conversion of XVIII via the 3 alpha,6 alpha-diol to the 3 alpha,6 alpha-ditosylate, followed by heating with potassium acetate in dimethylformamide and subsequent hydrolysis gave XXI. Full 1H and 13C NMR assignments are presented for VIII, XXI, and intermediates involved in their synthesis. 13C NMR assignments for 3 alpha,6 alpha-dihydroxy-5 beta-steroids have been corrected, and stereochemical assignments were established for the side-chain methylene protons of VIII, XXI, and most synthetic intermediates. Compound VIII lowered the levels of HMG-CoA reductase activity in CHO-K1 cells and in HepG2 cells with a potency comparable to that of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I). In contrast, 25,26,26,26,27,27,27-heptafluorocholest-5-en-3 beta-ol had little or no effect on reductase activity in CHO-K1 cells. These combined results indicate that metabolism of 3 beta-hydroxy-5 alpha-cholest-8(14)-en-15-one (I) to 26- and 25-oxygenated species is not required for the suppressive action of I on the levels of HMG-CoA reductase activity in CHO-K1 cells and HepG2 cells.
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PMID:Inhibitors of sterol synthesis. Chemical synthesis and properties of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one and 25,26,26,26,27,27,27-heptafluorocholesterol and their effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells. 824 28

In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bactericidal activity against both Gram-negative and Gram-positive bacteria. In addition, squalamine is fungicidal and induces osmotic lysis of protozoa. The chemical structure of the antibiotic 3 beta-N-1-(N-[3-(4-aminobutyl)]- 1,3-diaminopropane)-7 alpha,24 zeta-dihydroxy-5 alpha-cholestane 24-sulfate has been determined by fast atom bombardment mass spectroscopy and NMR. Squalamine is a cationic steroid characterized by a condensation of an anionic bile salt intermediate with spermidine. The discovery of squalamine in the shark implicates a steroid as a potential host-defense agent in vertebrates and provides insights into the chemical design of a family of broad-spectrum antibiotics.
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PMID:Squalamine: an aminosterol antibiotic from the shark. 843 93

A facile and regiocontrolled procedure for the preparation of 5-beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol-3-O-beta-D-glucuronide and its corresponding C-26 analogue is described. The method involves direct coupling of bile alcohols, namely, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol to methyl (tetra-O-acetyl-beta-D-glucopyranuronate) in the presence of a Lewis acid, tin(IV) chloride, in dichloromethane. The resulting anomeric pairs of 1,2-trans- and 1,2-cis-glucuronides of tetrols were resolved by analytical and preparative thin-layer chromatography, and their identities were established by high-resolution 1H NMR spectroscopy and by chemical-ionization and fast-atom-bombardment mass spectrometry. The method described has a practical advantage over the traditional two-step synthesis involving bromides as it is more efficient and uses inexpensive and less toxic materials. It is suggested that these compounds will be useful for studying permeability of the blood-brain barrier in cerebrotendinous xanthomatosis (CTX).
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PMID:Bile alcohol glucuronides: regioselective O-glucuronidation of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol. 845 7

The O-specific polysaccharide component of the lipopolysaccharide produced by Fusobacterium necrophorum is of the teichoic acid type, with repeating units connected by phosphoric diester linkages. Dephosphorylation of the polysaccharide by treatment with aqueous hydrogen fluoride yielded a carbohydrate composed of a trisaccharide linked to an acidic component. This product, and the polysaccharide, were investigated by chemical methods and 1H-, 13C-, 31P- and 15N-NMR spectroscopy and the former also by fast-atom-bombardment mass spectrometry. It is proposed that the polysaccharide is composed of repeating units having the following structure, in which Fuc represents fucose (6-deoxy-galactose), Am represents an acetamidino group and Sug 2,4-diamino-2,4,6-trideoxy-D-glucose ('bacillosamine') acetylated at the 2-position and acylated with a (S)-3-hydroxybutanoic acid at the 4-position. The acid was identified as a 2-amino-2-deoxy-2-C-methyl-pentonic acid (2-amino-2-methyl-3,4,5-trihydroxypentanoic acid). The configuration of this acid remains to be determined. [formula: see text]
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PMID:Structural studies of the O-antigenic polysaccharide of Fusobacterium necrophorum. 846 51

The interaction of the cationic tridecapeptide alpha-melanocyte stimulating hormone (alpha-MSH) and the biologically more active analog [Nle4, DPhe7]-alpha-MSH with lipid membranes was investigated by means of ESR of spin probes incorporated in the bilayer, and NMR of deuterated lipids. All spin labels used here, stearic acid and phospholipid derivatives labeled at the 5th and 12th position of the hydrocarbon chain, and the cholestane label, incorporated into anionic vesicles of DMPG (1,2-dimyristoyl-sn-glycero-3-phosphoglycerol) in the liquid-crystalline phase, indicated that both peptides decrease the motional freedom of the acyl chains. No peptide effect was detected with neutral lipid bilayers. Changes in the alpha-deuteron quadrupolar splittings and spin lattice relaxation time of DMPG deuterated at the glycerol headgroup paralleled the results obtained with ESR, showing that the peptides cause a better packing both at the headgroup and at the acyl chain bilayer regions. The stronger effect caused by the more potent analog in the membrane structure, when compared to the native hormone, is discussed in terms of its larger lipid association constant and/or its deeper penetration into the bilayer.
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PMID:Spin label and 2H-NMR studies on the interaction of melanotropic peptides with lipid bilayers. 866 38

Cholestane-derived gem-dihydroperoxides and tetraoxanes were synthesized starting from 5 alpha- and 5 beta-cholestan-3-ones by acid-catalyzed addition of hydrogen peroxide to the ketone. They were characterized by IR, NMR, and mass spectroscopy analysis aided by molecular mechanics calculations, and, in the instance of 5 beta-cholestane-3 alpha,3 beta-dihydroperoxide (6), by x-ray analysis. The synthesized compounds were tested in vitro against Plasmodium falciparum Sierra Leone (D6) and Indochina (W2) malaria clones. All compounds were inactive to both clones, with the exception of tetraoxane 7a, which exhibited modest activity toward D6 clone with IC50 = 155 nM.
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PMID:Steroidal geminal dihydroperoxides and 1,2,4,5-tetraoxanes: structure determination and their antimalarial activity. 898 37

A rapid and easily performed procedure for the synthesis of 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol by means of an efficient homologation sequence of the intermediate, 3 alpha, 7 beta, 12 alpha-triformyloxy-24-oxo-25-diazo-25-homo-5 beta-cholane is described. The reaction sequence involved treating the intermediate, alpha-diazoketone in methanol with 3% AgNO3 or Ag2O, anhydrous Na2CO3, Na2S2O/H2O resulting in the formation of homoursocholic acid in high yield. Esterification of the homoursocholic acid in methanol containing a catalytic amount of methanesulfonic acid under microwave irradiation conditions gave methyl homourscholate. The subsequent treatment of methyl homoursocholate with methyl magnesium iodide provided 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol in 88% yield. The products and synthetic intermediates prepared in these studies were fully characterized by the results of 1D and 2D NMR, and high-resolution mass spectral studies. These studies will help in further investigation of the defect of cholic acid biosynthesis in patients with cerebrotendinous xanthomatosis (CTX) as well as other inborn errors of bile acid metabolism.
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PMID:7 beta-hydroxy bile alcohols: facile synthesis and 2D 1H NMR studies of 5 beta-cholestane-3 alpha, 7 beta, 12 alpha, 25-tetrol. 917 27

3 beta-Hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one (4) has been prepared as part of a program to synthesize 15-ketosterols that are not readily metabolized to cholesterol or side-chain oxygenated species. Saponification of 3 beta-acetoxy-5 alpha-chola-8(14),23-dien-15-one (5) followed by lithium-ammonia reduction with a bromobenzene quench gave 3 beta-hydroxy-5 alpha-chol-23-en-15-one (6). Addition of (CF3)2CFI to 6 in the presence of triethylborane gave an iodide preparation, which was reduced to 4 with tributyltin hydride (71% overall yield of 4 from 5). The 23-iodide preparations consisted of 6:1 mixtures of (23R)-3 beta-hydroxy-23-iodo-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one (9a) and its C-23 epimer 9b with variable amounts of 4. Compound 4 was also prepared by lithium-ammonia reduction of the delta 8(14) analogs of 4 and iodides 9a and 9b. The presence of small amounts of 6 in the latter product suggested a side reaction involving cleavage of the C24-C25 bond with loss of a (CF3)2CF radical. Also prepared were 25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestane-3 beta, 15 alpha-diol, its 15 beta epimer, the 7 alpha-methyl analog of 4, 3 beta-hydroxy-7 alpha-methyl-5 alpha-cholestan-15-one (16), and (25R)-3 beta,26-dihydroxy-5 alpha-cholestan-15-one. Full 1H and 13C-NMR data of high precision with complete signal assignments are given for all new compounds. Definitive 1H-NMR stereochemical assignments of the C-24 protons were established for most sterols with a C8H17 side chain based on analysis of the downfield H-24 resonance in a 750-MHz spectrum of 16. Detailed electron-impact mass spectral data are presented together with a summary of major fragmentation patterns for 15-hydroxy- and 15-ketosteroids with and without a delta 8(14) bond.
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PMID:Inhibitors of sterol synthesis. Synthesis and spectral properties of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholestan-15-one. 917 93

Steroids were isolated from the blood-sucking leech species Hirudo medicinalis and their structure was studied with one- and two-dimensional NMR spectroscopy (DQF-COSY and HMQC), GC-MS and ESI-MS spectrometry. Fractionating leech lipid using silicic acid chromatography led to the isolation of cholesterol in an early chloroform-eluted peak. Only minor traces of cholest-4-en-3-one, 4 beta-methylcholesterol, and sitosterol were present. The subsequent acetone-eluted fraction contained steroidtriols that were further purified by preparative TLC; these included cholest-7-ene-3,5,6 triol, cholest-4,7-diene-3,6,15 triol and to a lesser amount, cholestane-3,5,6 triol. A developmental study on cholesterol content in the leech showed that it is also the principal steroid in embryonic and freshly hatched leeches prior to feeding. The abundance of cholesterol, comprising approximately 5% of the total leech lipid, suggests that H. medicinalis, a blood sucking leech, has adapted itself fully to its mammalian host in terms of its steroid content. It remains to be seen whether lipids are directly transferred from the host to the parasite or whether leeches have evolved mechanisms to synthesize their own steroids.
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PMID:Cholesterol and its derivatives, are the principal steroids isolated from the leech species Hirudo medicinalis. 982 41

Seven new aminosterols related to squalamine (8) were isolated from the liver of the dogfish shark Squalus acanthias. Their structures (1-7) were determined using spectroscopic methods, including 2D NMR and HRFABMS. These aminosterols possess a relatively invariant cholestane skeleton with a trans AB ring junction, a spermidine or spermine attached equatorially at C3, and a steroidal side-chain that may be sulfated. The structure of the lone spermine conjugate, 7 (MSI-1436), was confirmed by its synthesis from (5alpha,7alpha, 24R)-7-hydroxy-3-ketocholestan-24-yl sulfate. Some members of this family of aminosterols exhibit a broad spectrum of antimicrobial activity comparable to squalamine.
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PMID:Aminosterols from the dogfish shark Squalus acanthias. 1084 74


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