Steroid phenolic, formation

C3. Collins, D. C., and Layne, D. S., The formation by the rabbit of iV-acetylglucos-aminides of steroid phenolic sulfates. Steroids 13, 783-792 (1969). 

An unusual reaction was been observed in the reaction of old yellow enzyme with a,(3-unsat-urated ketones. A dismutation took place under aerobic or anaerobic conditions, with the formation from cyclohex-l-keto-2-ene of the corresponding phenol and cyclohexanone, and an analogous reaction from representative cyclodec-3-keto-4-enes—putatively by hydride-ion transfer (Vaz et al. 1995). Reduction of the double bond in a,p-unsaturated ketones has been observed, and the enone reductases from Saccharomyces cerevisiae have been purified and characterized. They are able to carry out reduction of the C=C bonds in aliphatic aldehydes and ketones, and ring double bonds in cyclohexenones (Wanner and Tressel 1998). Reductions of steroid l,4-diene-3-ones can be mediated by the related old yellow enzyme and pentaerythritol tetranitrate reductase, for example, androsta-A -3,17-dione to androsta-A -3,17-dione (Vaz etal. 1995) and prednisone to pregna-A -17a, 20-diol-3,ll,20-trione (Barna et al. 2001) respectively. 

Actinomycetes can metabolize a wide variety of organic substrates, including organic compounds that are generally not metabolized, such as phenols and steroids. They are also important in the metabolism of heterocyclic compounds such as complex nitrogen compounds and pyrimidines [42,49]. The breakdown products of their metabolites are frequently aromatic, and these metabolites are important in the formation of humic substances and soil humus [42,49]. 

The formation of sulfate esters is a major route of conjugation for various types of hydroxyl group, and may also occur with amino groups. Thus, substrates include aliphatic alcohols, phenols, aromatic amines, and also endogenous compounds such as steroids and carbohydrates (Figs. 4.56 and 4.57). 

Among the variety of sulfate esters formed by living cells are the sulfate esters of phenolic and steroid compounds excreted by animals, sulfate polysaccharides, and simple esters, such as choline sulfate. The key intermediate in the formation of all of these compounds lias been shown to be 3 -phosphoadenosine-5/-phosphosulfate (PAPS). This nucleotide also serves as an intermediate in sulfate reduction. 

SBSE can be successfully used in the analysis of environmental samples [93-97] and for food analysis [98, 99]. PDMS is the most commonly used polymer, primarily because of its thermal stability and durability. SBSE has been modified by application of derivatization with different reagents (acetic anhydride, BSTFA, etc) [100-104]. This approach is suitable for the extraction of compounds requiring derivatization. The use of multistep derivatization with several extraction elements (each reaction is performed on a different stir bar) allows efficient extraction, desorption, and chromatographic analysis of compounds with different functional groups (e.g., phenols, steroids, amines, thiazoles, ketones). Acetic anhydride (ester formation), ethyl chloroformate (reaction of acids and amines), tetraethyloborane, and sodium bis-trimethylotrifluoroacetamide have been used for extraction and simultaneous derivatization [105]. 

The substrate arachidonic aeid, whieh often leads to formation of inflammatory prostaglandins, is stored in tissues as one of a number of phospholipids these compounds, as the name indicates, comprise complex phosphate-containing esters. The antiinflammatory corticosteroids inhibit the action of the enzyme, phospholipase A2, that frees arachidonic acid. The many undesired effects of those steroids has led to the search for non-steroidal inhibitors of that enzyme. A highly substituted indole derivative has shown good activity as a phospholipase A2 inhibitor. Alkylation of the anion from treatment of indole (32) with benzyl chloride affords the corresponding A-benzylated derivative (33). The methyl ether at the 4 position is then cleaved by means of boron tribromide to yield 34. Alkylation of the enolate from reaction of the phenol with sodium hydride with tert-butylbromoacetate affords the corresponding... 

Results listed in Table 25 show that substituents at a variety of positions have little effect on the course of rearrangement of steroidal i,4-dien-3 0nes, except in regard to yields of the j>ara phenols. Certain structural changes, however, result in the formation of "meta (3-hydroxy-i-methyl) products. This occurs when the compound contains a A -double... 

STs are simple phenols such as 4-nitrophenol, phenolic catecholamine neurotransmitters such as dopamine, phenolic steroids such as the estrogens, non-phenolic hydroxy-steroids such as dehydroepiandrosterone (DHEA) and in plants, flavonols such as quercetin. Cytosolic STs are also actively involved in the Al-sulfation of alkyl- and aryl-amines, as well as alkyl- and arylamides leading in some cases to the formation of unstable metabolites. 

Compounds ofher fhan phenols are also capable of giving color reactions with iron(III). Of special inferesf are fhe ones forming red or violet complexes formate and acetate, benzoate, acetylacetone, and antipyrine. Even some steroids can give red complexes with iron(lll) through enolization of a carbonyl group.Selectivity in the test method is given by the color of fhe complex and its stability even after adding acetic acid. 

The formation of 2-methoxyestrogens from the estrogens requires also 2-hydroxylation of the phenolic steroids. It has recently been shown by Fishman et al. (1960a) that this reaction does in fact occur in human tissues. Following the injection of estradiol-l7 9-i5-C into a 22-year-old man, 2-hydroxyestrone was isolated from the urine. The extent of 2-hydroxylation appears to be considerable about 12% of the administered radioactivity was recovered from the urine as radioactive 2-hydroxyestrone. An extensive study on 2-hydroxylation of estriol by rat liver in vitro was carried out by King (1961 a,b). It was found that the 2-hydroxylase activity is limited to the microsomal fraction and requires either NADHj or NADPHz, and possibly a folic acid derivative ATP appears to stimulate the 2-hydroxylase. 

Conjugation of phenols, aliphatic and steroid alcohols with sulfate occurs in mammals, birds, reptiles, amphibia, but not in fish. In addition, active sulfate in the presence of transferase will conjugate aromatic amines and form sulfamates [70] in mammals, birds, and spiders. The synthesis of sulfate derivatives occurs in the soluble fraction of liver homogenates through the formation of adenosine-5 -phosphosulfate (APS) and 3 -phosphoadenosine-5 -phosphosulfate (PAPS) [21]. The reactions may be written as follows ... 

Contrary to plants, higher animals can not synthesize compounds with benzenoid rings from aliphatic precursors, the very few exceptions include estrone and related phenolic steroids (Singleton, 1981). Plants are the source of nearly all the phenols found in animals. Even the phenols that are essential for animals (such as the catechol amines and phenolic indole amines involved in nerve action and associated effects), the vitamin E tocopherols, the vitamin K napthoquinones or menadiones, the ubiquinone benzoquinones, thyroxine, the tyrosine of proteins, and the tyrosine-DOPA derivatives involved in melanin pigment formation, are all drawn either directly or indirectly from plants or are modified from an essential plant precursor, usually phenylalanine (Singleton and Kratzer, 1969). 

Sulphate conjugates, once called ethereal sulphates because of their extraction characteristics, are of two major types aryl or alkyl sulphates (which are esters of phenols or alcohols) and steroid sulphates. The sulphate moiety is transferred from the cofactor adenosine-3 -phosphate-S -phosphosulphate (PAPS) to an acceptor by enzymes known as sulphotransferases or sulphokinases. The enzymes which catalyse the formation of PAPS as well as the sulphokinases are in the soluble fraction of liver ... 

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