Cholestenone, from cholesterol

The reaction is illustrated by the preparation of cholestenone from cholesterol the double bond migrates from the Py to the ap position during the oxidation ... 

Dihydrocholesterol has been prepared by the reduction of cholestenone with sodium and amyl alcohoP and by the hydrogenation of cholesterol. In the presence of platinum black or platinum oxide, yields varying from 6.5 per cent to 40 per cent have been obtained in ether, acetone, ethyl acetate, and acetic acid. ... 

Cholestenone (derived from unreacted cholesterol) and progesterone were separated from deoxycorticosterone acetate (internal standard) by normal phase chromatography on a TSK-gel silica 150 column (4 mm x 250 mm)... 

Figure 9.85 Normal phase HPLC profiles of the reaction product of the cholesterol side chain cleavage system. Peaks were identified on the basis of their retention times. (i4) Without cholesterol oxidase treatment. Cholesterol (100 nmol) was incubated with cytochrome P450scc (70 pmol) in the presence of adrenodoxin, adrenodoxin reductase, and an NADPH-generating system. Monitoring was at 214 nm. Peaks 1, cholesterol 2, pregnenolone 3, deoxycorticosterone acetate (internal standard) (B) The reaction mixture of (A) was further incubated with cholesterol oxidase at 37°C for 10 minutes. Monitoring was at 240 nm. Peaks 1, cholestenone 2, progesterone 3, deoxycorticosterone acetate (internal standard). (From Sugano et al., 1989.)...

The reaction time and concentrations used depend on the reactants. Reaction is usually effected at 60°. Formation of condensation products from the ketones is largely repressed by working in inert solvents such as benzene, dioxan, and toluene. Aluminum isobutoxide, as well as the isopropoxide, has proved its value as metal alkoxide usually it is added to the reaction mixture in the proportion of 0.5 mole per mole of alcohol. Compounds containing nitrogen and halogen can also be oxidized by the Oppenauer method. Dehydrogenation of cholesterol to cholestenone will be described as an example 454... 

The relationship of cholesterol to cholestanol has now been delineated. Early experiments of Schoenheimer ef al. (103, 104) and Rosenfeld and Webster (105) resulted in a proposal that cholesterol was metabolized to -cholestenone (XXIX), which was reduced to cholestanol or coprostanol (106) indeed. Baker and Greenberg (106) detected C-cholestanol in rat feces after administration of radioactive acetate. Anker and Bloch (107) and Stokes et al. (108) found efficient conversion of labeled J -cholestenone to tissue cholestanol in rats. Cholesterol was shown (109) to be a precursor of cholestanol in the adrenals, liver, and intestine of guinea pigs. With cholesterol-4- - C-4/3- H Werbin et al. showed that the cholestanol isolated from the adrenals contained as much as 14% of the tritium at positions 5 and 6, whereas the cholestanol obtained from liver and intestine was virtually devoid of tritium at these positions (110). Based on these observations they proposed the following possible pathway ... 

When human beings were fed cholesterol-D, the coprostanol isolated from the feces contained deuterium. Similarly, cholestenone-n (V) and copros-tanone-D (VI) each afforded coprostanol-n. Corroborative evidence for these transformations has also been obtained with a sapogenin derivative, 4-dehydrot ogenone (VII), identical with cholestenone in the A and B rings (Fig. 3). The E and F rings of the sapogenin are not normally... 

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