Sterols, oxidative degradation

Steroids and sterols represent an important class of drugs that are susceptible to oxidative degradation through the possession of alkene moieties. The oxidation of phenothiazines forms the sulfoxide moiety. 

We investigated the ratio of free sterol to steryl ester in auxotrophic cells. Although the principal sterol of yeast is ergosterol, we have found that cholesterol can satisfy the sterol growth requirement of adapted yeast sterol auxotrophs and is readily esterified. We chose to use cholesterol for these experiments because of its stability against oxidative degradation and availability as a high purity radiolabeled compound. 

Figure 4 Peroxisomal fatty-acid (FA) /3-oxidation pathways. While saturated long-chain fatty acids (LCFA) are preferentially degrade in mitochondria, saturated very-long-chain fatty acids (VLCFA) and some LCFA are shortened by peroxisomal /3-oxidation. Degradation of pristanic acid, the product of phytanic acid a-oxidation, and the conversion of the cholesterol-derived 27-carbon bile-acid precursors dihydroxycholestanoic acid (DHCA) and trihydroxycholestanoic acid (THCA) to 24-carbon bile acids also require this pathway. The mechanism by which these substrates enter peroxisomes is unknown. Four enzymatic reactions serve to shorten the substrates by either two (LCFA, VLCFA) or three (pristanic acid, DHCA, THCA) carbon atoms. The 2-methyl group of the latter substrates is shown in brackets. SCPx thiolase refers to the thiolase activity of sterol carrier protein x.

Bacterial removal of sterol side chains is carried out by a stepwise P-oxidation, whereas the degradation of the perhydrocyclopentanophenanthrene nucleus is prevented by metaboHc inhibitors (54), chemical modification of the nucleus (55), or the use of bacterial mutants (11,56). P-Sitosterol [83-46-5] (10), a plant sterol, has been used as a raw material for the preparation of 4-androstene-3,17-dione [63-05-8] (13) and related compounds using selected mutants of the P-sitosterol-degrading bacteria (57) (Fig. 2). 

Sterols are seldom detected in archaeological residues due to their low concentration and the tendency to undergo chemical degradation. In any case, the presence of sterols or of their oxidation products in a sample can help distinguish between animal and plant lipid materials cholesterol is the most abundant animal sterol, while campesterol and sitosterol are the two major plant ones. 

Degradation of the sterol stigmasterol to progesterone is achieved by the sequence shown in Figure 5.120. The double bond in the side-chain allows cleavage by ozonolysis, and the resultant aldehyde is chain shortened via formation of an enamine with piperidine. This can be selectively oxidized to progesterone. In this sequence, the ring A transformations are carried out as the... 

Valuable minor components Fat degradation products Contaminants Tocopherols, sterols, squalene, oryzanol Trans-fatty acids, polymeric and oxidized triacylglycerols, cyclic fatty acids Pesticides, polycyclic aromatic hydrocarbons, polychlorinated biphenyls, dioxins, furans ... 

XLIX) was degraded by Hofmann eliminations (Fig. 6) to a mixture of dienes which w as oxidized to X( — )-3-methoxyadipic acid. The absolute configuration of this acid was knowui from earlier work in which it had been a key intermediate in establishing the absolute configuration of sterols 20) and led to the 3 R configuration for j8-erythroidine. 

Barbier-Wieland degradation. Stepwise carboxylic acid degradation of aliphatic acids (particularly in sterol side chains) to the next lower homo log. The ester is converted to a tertiary alcohol that is dehydrated with acetic anhydride, and the olefin oxidized with chromic acid to a lower homologous carboxylic acid. 

Amino acid oxidation catalase and peroxidase reactions sterol degradations in plants, glyoxylate cycle reactions... 

Figure 7.4. The activation of spironolactone to products that inactivate sterol 17a-hydroxylase by covalent attachment to the protein, and hepatic P450 3A by degradation of the heme group, occurs during oxidation of the free thiol group unmasked by the action of a thiolesterase.

---