Steroid sulfates structures

An Acanthodendrilla sp. from Japan contained ten steroidal sulfates, acanthosterol sulfates A-J (561-570). Acanthosterol sulfates I (569) and J (570) showed antifungal activity against Saccharomyces cervisiae and its mutants [463]. Clathsterol (571), was isolated from the Red Sea sponge Clathria sp. The structure was established mainly by interpretation of spectral data and a chemical transformation. Clathsterol (571) was active against HIV-1 reverse transcriptase (RT) at a concentration of 10 iM [464]. Toxadocia zumi contains three sterol sulfates (572-574) that are antimicrobial, cytotoxic, ichthyotoxic and larvicidal [465]. 

Several physiologic roles for CS have been postulated. First, it has been suggested that the presence of CS in erythrocytes (about 700 fig of CS are present in 100 ml erythrocytes [125]) stabilizes the erythrocyte membrane [130]. Thus, CS was found to reduce hemolysis up to 56% in hypotonic solutions, whereas several other steroid sulfates and cholesterol conjugates were devoid of antihemolytic activity [125]. Furthermore, the presence of CS had a critical influence on the disc shape of erythrocytes in hypotonic solution without CS, erythrocytes tended to become spherical and extend spicules [131]. A second postulated role of CS relates to spermatozoa. It has been suggested that CS stabilizes the membranes of these cells and that it may provide a structural trigger for capacitation [132,133]. Thus, CS is present in spermatozoa (15 fig/lO cells) as well as in seminal plasma, and appears to be concentrated in the acrosomal region [132]. On the other hand, sterol sulfatase activity is present in the human female reproductive tract [133]. There is no direct evidence, however, that CS contributes to the sperm membrane modification reactions that occur in association with fertilization. 

Steroid sulfates and glucuronides are best analyzed in the negative-ion ESI mode, where they give [M-H] ions. Structural information can then be obtained by performing MS/MS (Figure 14.5). However, steroids and bile acids exist in biological samples as part of complex mixtures and an [M-H] ion is likely to represent a number of isomers. These can, however, be separated by LC prior to ESI [27] and partially characterized by MS/MS [34]. 

Structures of some steroid sulfates and glucuronides found in urine. Also shown are the structures of plamitic and stearic acids. 

Structures of some steroid sulfates found in plasma. 

Yun, S-S., Scott, A. P., and Li, W. (2003). Pheromones of the male sea lamprey, Petromyzon marinusL. structural studies on a new compound, 3-keto allocholic acid, and 3-keto petromyzonol sulfate. Steroids 68,297-304. 

The structure of sokotrasterol sulfate (548), isolated from sponges of the family Halichondriidae was determined by X-ray analysis [453-455]. The steroid, 26-norsokotrasterol sulfate (549), was isolated from the marine sponge Trachyopsis halichondrioides and was identified by NMR spectroscopic analysis [456]. 

An unusual 6a-sterol sulfate (557) was isolated from Dysidea fragilis, from the Venetian lagoon and displayed cytotoxicity against two different tumour cell lines in vitro [460]. Tamosterone sulfates (558-559) are a C14 epimeric pair of polyhydroxylated sterols isolated from a new species of Oceanapia [461]. The Japanese marine sponge Epipolasis sp. contained the steroid polasterol B sulfate (560) along with the known compound halistanol sulfate (532). The structure of compound 560 was determined on the basis of spectroscopic evidence and a chemical conversion [462]. 

Steroid hormones are generally converted into inactive metaboic excretion products in the liver. Reactions include reduction of unsaturated bonds and the introduction of additional hydroxyl groups. The) resulting structures are made more soluble by conjugation with curonic acid or sulfate (from PAPS, see p. 160). Approximate ) twenty to thirty percent of these metabolites are secreted into the bile and then excreted in the feces, whereas the remainder ae t released into the blood and filtered from the plasma in the kidney, passing into the urine. These conjugated metabolites are fairb1 water-soluble and do not need protein carriers. 

Several sulfated polyhydroxysterols have been recently isolated from sponges. Most of these natural products are characterized by the 2p,3a,6a-tri-0-sulfate functions together with additional alkylation in the side chain. These steroids are of interest not only because of their structures but... 

In 2002, through the use of nuclear magnetic resonance (NMR) and mass spectrometry/mass spectrometry (MS/MS) analysis, the planar and partial stereostructure of a SAAF from the egg-conditioning medium of C. intestinalis w s elucidated to be a previously uncharacterized sulfated steroid 3,4,7,26-tetrahydroxycholestane-3,26-disulfate (30).73 Its structure was deduced from only 4p.g (6 nmol) of sample. Thus, SAAF may represent the smallest amount of sample used in the structure elucidation of novel nonpeptidic or nonoligosaccharide natural products.74... 

From the viewpoint of the steroid structure, SAAF (30) has several unique features. The hydroxylation pattern at the 3, 4, 7, and 26 positions of a cholestane skeleton has not been reported in any other natural products.73 The positions of the C-3 and C-26 sulfate esters are also unique among sulfated polyhydroxysterols of marine origin. In general, steroid hormones act on nuclear receptors and activate gene expression. However, the chemotactic behavior of sperm occurs within a few seconds, and the sperm nucleus is condensed, indicating that genes could not be expressed in the sperm. Furthermore, since SAAF has a hydrophilic nature due to the presence of two hydroxyl and two sulfated esters, it may bind to receptors located on the sperm plasma membrane. 

Numerous squalamine analogs have been prepared and examined for biological activity (Figure 9.1). The squalamine structure has been varied through the length of the polyamine chain [41-44] the nature of the anionic functional group [41] the position of the polyamine [43-45], sulfate [45,46], and free hydroxyl [41,43,44,47] on the steroid scaffold the stereochemistry and substitution at C-3, C-7, and C-24 [41-44] the length of the steroid side chain [41,45,46] and the unsaturation of the steroid [43,44]. 

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