Steroid ethers

Residual aromatic ether concentrations are determined from the absorbance at 278 mfi of the crude reduction products in methanol solution. Steroidal ether concentrations of 1 mg/ml are employed. The content of 1,4-dihydro compound is determined, when possible, by hydrolysis to the a, -unsaturated ketone followed by ultraviolet analysis. A solution of the crude reaction product (usually 0.01 mg/ml cone) in methanol containing about 1/15 its volume of water and concentrated hydrochloric acid respectively is kept at room temperature for 2 to 4 hr. The absorbance at ca. 240 mfi is measured and, from this, the content of 1,4-dihydro compound can be calculated. Longer hydrolysis times do not increase the absorbance at 240 mp.. 

Lithium bromide-Boron trifluoride etherate. Aliphatic ethers can be cleaved by reaction with lithium bromide and boron trifluoride etherate in acetic anhydride at room temperature for 30 hrs. Methoxycyclohexane, for example, is converted into a 7 1 mixture of acetoxycyclohexane and cyclohexene. Saturated steroid ethers are cleaved to mixtures of enes and acetates under these conditions choles-teryl methyl ether gave about equal parts of cholesteryl acetate and cholesteryl bromide. However, Narayanan reports that the lithium halide is not essential and indeed often detrimental. Thus cholesteryl methyl ether treated with boron trifluoride etherate and acetic anhydride in ether at 0° (14 hrs.) gave cholesteryl acetate in 93% yield. 

ErcoU, A., Gardi, R. D4-3-keto steroidal ethers. Paradoxical dependency of their effectiveness on the administration route. J. Am. Chem. Soc. 1960, 82, 746-748. 

The only reactions which proceeded with good yields were those of phenanthrenequinone. With the exceptions of the steroid ethers, the ether was used as solvent and 1,4-adducts (87) could be isolated in high yield when irradiations were performed at A >3900 A. At shorter wavelengths the dioxane and anisole adducts rearranged to the corresponding 1,2-adducts (88), rearrangement of the anisole adduct being quite facile. The 1,4-adducts of aliphatic ethers were unstable in air 127>. 

Salmond of the Upjohn Company has reported several methods for the preparation of 25-hydroxycholesterol from the intermediate aldehyde (52). In a most efficient process the aldehyde was condensed with the Wittig reagent (59) obtained in three easy steps from isoprene. The product diene (61) could be selectively oxidized at the 24,25-double bond to give epoxide (62) as a mixture epimeric at C-24. Catalytic hydrogenation concomitantly reduced the 22,23-double bond and the epoxide to give the 25-hydroxylated cholesterol side chain. Reversal of the /-steroid ether... 

The steroidal ether was electrolyzed in a two-compartment cell using Pt working... 

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