Sterols ketones

Dreier et al. [44] determined sterols in lacustrine sediments. Samples of wet lacustrine sediments were heated under anoxic conditions at 150, 175, 200 and 250°C for five days at 175°C for five days with influx of potassium hydroxide and methanol to remove sterols and at 175°C for 12, 18, 24 and 48h, after which extraction was performed. Heating the sediment increased the amounts of extractable sterols provided that the temperature did not exceed 200°C, because degradation became rapid above that temperature. The behaviour of sterol ketones was similar, but the temperature limit was slightly higher. The various levels of the sterols extracted are tabulated 4-methylsterols had a high stability towards thermal degradation under the conditions used. 

Oppenauer, R. V. Dehydration of secondary alcohols to ketones. I. Preparation of sterol ketones and sex hormones. Reel. Trav. Chim. Pays-Bas 1937, 56,137-144. 

Verley, A., Bull. soc. chim. France, Sur 1 change de groupements fonctionnels entre deux mol cules. Passage des c tones aux alcohols et inversement. 37, 537,1925. Oppenauer, R. V., Dehydration of secondary alcohols to ketones. I. Preparation of sterol ketones and sex hormones. Reel. Trav. Chim. Pays-Bas, 56, 137,1937. 

General metabolic significance. Acetyl CoA is a central compound of cell metabolism linking catabolic processes with generation of biological energy. Acetyl CoA is also a starting metabolite for biosynthesis of fatty acids, sterols, ketone bodies, etc. 

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 ... 

In this chapter, we have examined the use of cells and enzymes to chemically transform lipids. We have had to be selective and have predominantly focused attention on the transformation of sterols and steroids. We first explained why these compounds were commercially important and why they only occur in low concentrations in natural systems. We pointed out that a very large number of reaction types are possible, but those which have found greatest use include stereospedfic hydroxylations, alcohol/ketone interconversion, hydrolysis, conjugation and isomerisation. 

Pharmacologically active allenic steroids have already been examined intensively for about 30 years [5], Thus, the only naturally occurring allenic steroid 107 had been synthesized 3 years before its isolation from Callyspongia diffusa and it had been identified as an inhibitor of the sterol biosynthesis of the silkworm Bombyx mori (Scheme 18.34) [86d], At this early stage, allenic 3-oxo-5,10-secosteroids of type 108 were also used for the irreversible inhibition of ketosteroid isomerases in bacteria, assuming that their activity is probably caused by Michael addition of a nucleophilic amino acid side chain of the enzyme at the 5-position of the steroid [103, 104]. Since this activity is also observed in the corresponding /3,y-acetylenic ketones, it can be rationalized that the latter are converted in vivo into the allenic steroids 108 by enzymatic isomerization [104, 105],... 

In contrast to the other large cats, the urine of the cheetah, A. jubatus, is practically odorless to the human nose. An analysis of the organic material from cheetah urine showed that diglycerides, triglycerides, and free sterols are possibly present in the urine and that it contains some of the C2-C8 fatty acids [95], while aldehydes and ketones that are prominent in tiger and leopard urine [96] are absent from cheetah urine. A recent study [97] of the chemical composition of the urine of cheetah in their natural habitat and in captivity has shown that volatile hydrocarbons, aldehydes, saturated and unsaturated cyclic and acyclic ketones, carboxylic acids and short-chain ethers are compound classes represented in minute quantities by more than one member in the urine of this animal. Traces of 2-acetylfuran, acetaldehyde diethyl acetal, ethyl acetate, dimethyl sulfone, formanilide, and larger quantities of urea and elemental sulfur were also present in the urine of this animal. Sulfur was found in all the urine samples collected from male cheetah in captivity in South Africa and from wild cheetah in Namibia. Only one organosulfur compound, dimethyl disulfide, is present in the urine at such a low concentration that it is not detectable by humans [97]. 

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. 

Grimalt JO, Fenandez P, Bayona JM, Albaiges J, Assessment of fecal sterols and ketones as indicators of urban sewage inputs to coastal waters, Environ Set Technol... 

Rog, T., Stimson, L.M., Pasenkiewicz-Gierula, M., Vattulainen, I., Karttunen, M. Replacing the cholesterol hydroxyl group with the ketone group facilitates sterol flip-flop and promotes membrane fluidity. J. Phys. Chem. B 2008, 112, 1946-52. 

Healthy, well-nourished individuals produce ketone bodies at a relatively low rate. When acetyl-CoA accumulates (as in starvation or untreated diabetes, for example), thiolase catalyzes the condensation of two acetyl-CoA molecules to acetoacetyl-CoA, the parent compound of the three ketone bodies The reactions of ketone body formation occur in the matrix of liver mitochondria. The six-carbon compound /3-hydroxy-/3-methylglutaryl-CoA (HMG-CoA) is also an intermediate of sterol biosynthesis, but the enzyme that forms HMG-CoA in that pathway is cytosolic. HMG-CoA lyase is present only in the mitochondrial matrix. 

Oppenauer was able to shift the equilibrium towards the oxidation of a number of sterols, by employing an excess of cheap acetone as oxidant and taking advantage of some very favourable thermodynamics in oxidations, in which an alkene enters into conjugation with the resulting ketone. 

The so-called Oppenauer oxidation proved to be extremely successful in the oxidation of sterols. On the other hand, its application—in the original formulation—to the obtention of ketones outside the field of steroids and to the preparation of aldehydes met a more limited success because of less favourable thermodynamics and side reactions, induced by the basic character of the aluminium alkoxides. 

Inspection of Table 6.1 shows that the classical oxidation of sterols on the alcohol at the 3-position, using acetone as oxidant, works efficiently thanks to the migration of the alkene. Thus, the oxidation of cholesterol with acetone (E0 = 129 mV) must proceed via the thermodynamically disfavoured A5-cholesten-3-one (E0 = 153 mV) that evolves to the very stable A4-cholesten-3-one (E0 = 63 mV). In fact, acetone lacks oxidizing power for the obtention of many ketones as well as for the preparation of virtually all aldehydes. 

The aluminium alkoxides present in the Oppenauer oxidation can cause some base-induced side reactions. Thus, quite typically during the oxidation of sterols possessing homoallylic alcohols, a migration of the alkene into conjugation with the resulting ketone is observed (see pages 256 and 259).4... 

While the hydrocarbon fraction of insect cuticular lipids is certainly the most studied and has been shown to play a key role in a wide range of chemical communication, other lipids are often present on the surface of insects. The most common cuticular lipids in addition to hydrocarbons include a variety of types of esters, free fatty acids, primary and secondary alcohols, ketones and sterols. Triacylglycerols and the more polar phospholipids are not common components of insect cuticular lipids. In some cases, hydrocarbons are hydroxylated and metabolized to oxygenated components, and these products include some of the short range and contact pheromones of the housefly (Blomquist, 2003) and the German cockroach (Schal et al., 2003). The oxygenated cuticular lipids are discussed in Chapter 9 (Buckner, this book). 

None of the steroid molecules is colored so direct electronic spectrophotometric analyses must be done in the near UV range. The major chromophores are, of course, the aromatic ring, ketone, conjugated ketones, and ethynyl groups. With some exceptions prior derivatization reactions are generally required for the determinations of sterols. These reactions can be either reversible or irreversible. Ketal formation, for instance, is an example of the latter type color induction reactions are examples of the second kind. 

Liu and Zhou applied Roush s crotylboration to the stereoselective synthesis of the orostanal 70, a novel sterol that induces apoptosis in human acute promyelotic leukemia cells28 (Scheme 3.ly). The aldehyde 72, prepared from hyodeoxycholic acid methyl ester, underwent asymmetric reaction with crotylboronate (R,R)-43E to furnish 73. Hydrogenation of the terminal alkene followed by Swem oxidation gave the ketone 74. Methylenation of the ketone and removal of the protective groups afforded orostanal in 50% yield. 

Insect cuticular lipids consist of aliphatic material which is present on the outer layer of the integument. In most species, they consist of complex mixtures of hydrophobic compounds including straight-chain saturated, unsaturated, and methyl-branched hydrocarbons, wax esters, sterol esters, ketones, alcohols, aldehydes, and fatty acids (lj 4). In many insects, including the American cockroach (8) and the housefly (9), hydrocarbons are the predominant cuticular lipid component. 

As shown in Figure 2-23, oil breakdown during frying can be caused by oxidation and thermal alteration. Oxidation can result in the formation of oxidized monomeric, dimeric, and oligomeric triglycerides as well as volatile compounds including aldehydes, ketones, alcohols, and hydrocarbons. In addition, oxidized sterols may be formed. Thermal degra-... 

Paraffin followed by candelilla wax and microcrystalline waxes, and eventually by beeswax, are considered as the most effective moisture barriers derived from edible waxes (Morillon et al. 2002). There is no satisfactory chemical definition for the term wax which is used for a variety of products of mineral, botanical and animal origin that contain various kinds of fatty materials (Table 23.4). The term resins or lacs can also be used for plant or insect secretions that take place along resins ducts, often in response to injury or infection, and result in more acidic substances (Hernandez 1994). However, all waxes tend to contain wax esters as major components, that is, esters of long-chain fatty alcohols with long chain fatty acids. Depending on their source, they may additionally include hydrocarbons, sterol esters, aliphatic aldehydes, primary and secondary alcohols, diols, ketones, triacylglycerols, and so on. 

Roller Coasters (an up and a down roller coaster, for fiitty acid biosynthesis and degradation), and a musical review by the Ketones in the Ketone Playhouse. In the East, progressing through Channel 5, one arrives at the dark and mysterious Sterol Forest, where one may search for sex, but must beware of falling into Bile Bog. 

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