Cholestanol, structure

The ring structure of cholesterol cannot be metabolized to C02 and HfeO in humans. Rather, the intact sterol nucleus is eliminated from the body by conversion to bile acids and bile salts, which are excreted in the feces, and by secretion of cholesterol into the bile, which transports it to the intestine for elimination. Some of the cholesterol in the intestine is modified by bacteria before excretion. The primary compounds made are the isomers coprostanol and cholestanol, which are reduced derivatives of cholesterol. Together with cholesterol, these compounds make up the bulk of (neutral fecal sterols. 

Degradation of choles terol Mechanisms of choles terol disposal DEGRADATION OF CHOLESTEROL (p. 222) The ring structure of cholesterol can not be metabolized in humans. Cholesterol can be elim inated from the body either by conversion to bile salts or by secretion into the bile. Intestinal bacteria can reduce cholesterol to coprostanol and cholestanol, which together with cholesterol make up the bulk of neutral fecal sterols. 

Figure 9.22 Coprastanol and cholestanol, products of cholesterol reduction. Dotted lines indicate positions below the plane of the ring (trans with respect to -CH3 on position 10) solid lines indicate positions above the plane of the ring (cis with respect to -CH3 on position 10). Both structures are of the /3 type.

Figure 4 Structures of lecithin, cholestanol (cholesterol derivative), and chlorophyll b.

Although cholesterol is always the major sterol present, a few closely related sterols are detected in mammalian cells, namely 7-dehydrocholesterol (cholest-5,7-dien-3 -ol) [11], cholestanol (5a-cholestan-3j8-ol) [12,13], lathosterol (5a-cholest-7-en-3/8-ol) [14] and desmosterol (cholest-5,24-dien-3)8-ol) [15]. 7-Dehydrocholesterol can make up 6-9% of the sterol content in subcellular membranes and in skin [11]. The structures of the most relevant mammahan and plant sterols are given in Fig. 1. 

Esters of cholesterol cannot be directly attacked by the enzyme [60,61]. Rat liver microsomes catalyse 7a-hydroxylation of cholestanol at a rate comparable to that of cholesterol [62]. Since 7a-hydroxylation of cholestanol is stimulated after treatment with cholestyramine, it appears likely that the same enzyme is involved as in hydroxylation of cholesterol. Shght changes in the side chain lead to marked loss of activity [63,64]. Loss of a terminal methyl group reduces the rate to about 50% and addition of an ethyl group at C-24 (sitosterol) leads to almost complete loss of the activity. From a study with a great number of structurally closely related steroids, Aringer concluded that cholesterol 7a-hydroxylase requires a rather flat steroid (A", A or 5a) and an equatorial or quasi-equatorial hydroxyl group at C-3 [65]. 

Androgens, the male sex hormones, proved far more elusive that either the estrogens and progestins since they occur at much lower concentrations in biological fluids. The bioassay used to track the isolation in this case comprised the capon unit . This was the amount of extract that produced a 20% increase in the surface of a rooster s comb. The 15 mg of pure crystalline testosterone isolated in 1931 came from about 15 0001 of urine. The structural investigations of this series relied on the then newly discovered side chain oxidations of cholestanol (13-1) (Scheme 1.13). This method in essence comprised fairly drastic oxidation of reduced cholesterols of known stereochemistry at the A-B junction to afford in fairly low yield products in which the side chain at Cn had been consumed to leave behind a carbonyl group. One of these products proved to be identical with androsterone (13-2). That compound had in turn been obtained from a sequence of reactions starting from dehydroepiandrosterone (13-3) that had been isolated from male urine. 

We can readily infer from their structures that epicholestanol, with an axial OH, will be less stable than its isomer, cholestanol, which has an equatorial OH. This explains why cholestanol is observed to predominate in the equilibrium mixture (90%). For the same reason,epicoprostanol will be more stable than coprostanol, and hence will be the favored isomer. 

The terms a and are useful in describing the stereochemistry of steroid and carbohydrate systems. For steroid systems such as the isomers of 3-cholestanol in Figure 2.26, an a hydroxyl group is one that lies beneath the approximate molecular plane. ° ° Thus, 62 is 3-a-cholestanol. On the other hand, a /3 substituent lies above the approximate plane of the molecule, as shown by the structure of 3-j8-cholestanol (63). ° ... 

Scheme 1 Molecular structures of the cholesterol (a- and ff- epimers) and cholestanol fi-epimer) building blocks...

Weiss and coworkers reported a series of anthraquinone-containing systems based on either the cholesterol or the 5a -cholestanol unit (Scheme 7) that were proven effective gelators of organic liquids. The behavior of cholesteryl anthraquinone-2-carboxylate, 16, the anthraquinone-containing derivative of 9, has been investigated in detail [31,33,36-38]. It was shown that the structure and properties of 16 gels in n-alkanes and long-chain alcohols, at... 

Steroid units other than cholesterol or cholestanol have been used for the synthesis of ALS structures featuring anthraquinone or anthracene as A part (Scheme 9) [31,36]. Particularly those compoimds in which the steroidal unit lacks a C8Hi7 chain at C-17 failed to produce gels in any of the solvents where 7 and 9, for example, are effective [31]. Slight changes at the C-17 aliphatic chain, such as introduction of unsaturation (23) and/or ethyl group (24), were shown to have httle impact on the gelation ability [36]. Compound 25,... 

Following is the structural formula and ball-and-stick model of cholestanol ... 

Following is the structural formula and a ball-and-stick model of cholestanol.The only difference between this compound and cholesterol (Section 26.4) is that cholesterol has a carbon-carbon double bond in ring B. 

In several insects and in certain microorganisms which require cholesterol for growth, this requirement can be met or spared by cholestanol (Clayton, 1964 Smith, 1964). This sterol is generally not metabolized and is believed to replace cholesterol in structural elements of the cell (Clayton and Bloch, 1963). 

With these assumptions we prepared an auxotrophic organism with the appropriate genetic configuration for the experiments. Cholestanol was used as the simplest basic structure to feed to the organism as the starting point for ascertaining structural requirements for the sterols. 

---