3/?-Hydroxy sterols

Monodesmosidic S. s. have a high surface tension activity, form strongly foaming, soap-like solutions in water, and on direct introduction into the blood circulation cause hemolysis of red blood particles even at high dilution they thus act as potent plasma and frsh toxins. Digitonin forms poorly soluble 1 1 complexes with cholesterol and other 3/3-hydroxy- sterols, this property is used for the isolation and analysis of digitonin. 

The Windaus reaction, i.e., digitonin precipitation of 3-/3-hydroxy sterols by the formation of insoluble products, appears to have been introduced as a histochemical method by Leulier and Noel (1926). By this technique, abundant crystals are produced in the adrenal cortex and the other organs which form steroid hormones. like the Schultz test, however. 

In vitro studies by Roddick and Drysdale on the effect of tomatine on the leakage of peroxidases from liposomes also support the idea that tomatine binds membrane sterols. They detected a significant disruption of the liposome by tomatine, only if the membranes contained sterol and additionally this destabilization was pH-dependent [27]. Later it was demonstrated that liposome membranes containing sterols but lacking 30-hydroxy sterol were resistant to tomatine [28]. 

Topsentinols A through J, ten new 7-hydroxy sterols with unusual polyalkylated side chains, have been isolated from the Okinawan marine sponge Topsentia sp. 

Recovered starting material 3.5-7 % unidentified isomerization products 3-7 % the remainder of the reaction mixture consisted of hydroxy sterols which were not investigated. 

During the oxidative decarbonylation, the 15a-hydrogen is lost. Also, if squalene is converted to cholesterol in HjO, the 15 position of cholesterol is labeled. This led to the suggestion that C-15 was hydroxylated and that a 4,4-dimethyl-14a-formyl-cholest-7-ene-3)8,15-diol was the substrate for the oxidative decarbonylation. Several 15a-hydroxy sterols have been tested as precursors. One did not work, the other was converted only poorly [105]. The double bond at C-14 is probably reduced as the next step since A sterols are rarely encountered. NADPH would be a probable reductant. 

Structure-Activity Reiationship (SAR) Studies of 7-Hydroxy Sterols... 

All of the synthetic sterols were assayed in rad52 DNA-damaging and RAD bioassays and some selected analogs have also been tested for cytotoxicity to Vero cells the results are presented in Table 7. All synthetic 7a-hydroxy analogs showed activity in our DNA-damaging bioassay with 37 and 38 having activity comparable to natural sterols isolated from Pseudobersama mossambicensis. 7a-Hydroxy sterols were also active in Vero cell cytotoxicity assay. However, an inverse correlation between activity in the yeast assay and the cytotoxicity assay was noted. Thus, the 7a-hydroxy sterol which was the most active in the DNA-damaging assay was the epoxide 38, with... 

In contrast to 7a-hydroxy sterols the 7p-hydroxy analogs 45 and 46 were completely inactive in the yeast assay, but showed moderate cytotoxicity in the Vero cell assay. These results suggested that the bioactivity of 7p-hydroxy sterols may involve a different mechanism of action than their a-counterparts. The sp-hydroxy sterols 47, 48 and 49 were found to be inactive in the yeast assay regardless of their side-chain functionalities and were not tested in the Vero cell assay. The results also indicated the requirement of a hydroxy function at C-7 of the sterol nucleus for biological activity in this class of compounds. 

Two Other 3a-hydroxy sterols, sulfated at position 26, were isolated from a single specimen of a sea star collected in Antarctica. These sterols result from the oxidation of a hydroxyl at position 6, common among asterids. This starfish has not been identified to the genus level, but belongs to the family Asteriidae (De Marino et al., 1997a). 

In addition to A -3p-hydroxy-sterols Stellata clarella also contains 5a-cholestanol (147), 5a-ergostanol (256), and 5a-poriferastanol (257). The latter two must be counted as new to Porifera. 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

Unlike heliantholysin and congeners, the toxicity of metridiolysin is not prevented by sphingomyelin, but is inhibited by cholesterol in low concentration, as well as by certain related sterols (23). In addition, metridiolysin is activated by thiols such as dithiothreitol, and is reversibly inactivated by compounds having an affinity for SH-groups, such as p-hydroxy-mercuribenzoate. A third notable feature is that the action of metridiolysin on membranes involves, or is associated with, the formation of 33 nm rings demonstrable by electron microscopy of negatively stained preparations. 

Endogenous and exogenous androgens can be derivatized with trimethylsilyl (TMS) for hydroxy functions and by 0-methylation for ketones, and analyzed with GC-FID or GC-MS (Shimada et al., 2001). MS is more prevalent due to unequivocal identification and greatly increased sensitivity but FID is still used in laboratories for some steroids. Sterols have typically been analyzed by GC-FID and GC-MS with derivatization to optimize peak shape (Shimada et al., 2001), and bile acids can be derivatized with M-butyl ester-TMS ether and analyzed by GC-FID from plasma samples (Batta et al., 1998). Juricskay and Telegdy (2000) reported an assay capable of analyzing 28 steroids in urine samples using GC-FID. 

The first application of the manifold experiences gained in the field of bioreductions to substances of the cholic acid and sterol series is due to Kim. He showed that dehydrodesoxycholic acid is transformed by bottom yeast to 3-hydroxy-12-ketocholanic acid. Mamoli and Vercel-... 

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