SYNTHESIS OF SOME SULFUR CONTAINING STEROIDS DERIVED FROM CHOLESTEROL

Some sulfur containing steroids derived from cholesterol were synthesized for the study of their protective effect against ionizing radiation on mammals. On refluxing cholesteryl bromide with ethanolamine followed by suitable treatment three isomeric products were isolated in the form of 3 β-(2'-hydroxyethylamino)-△⁵-cholestene (I_a), 3a-(2'-hydroxyethylamino)-△⁵-cholestene hydrochloride (Ⅱ_b), and 6-(2'-hydroxyethylamino)-3:5-cyclocholestane hydrochloride (Ⅲ_b)from the reaction mixture. However, when the two were allowed to react at 200℃ in a bomb, only I_a and Ⅱ_b were obtainable. The i-structure is assigned to Ⅲ_b on the basis of its dextrorotatory power, negative bromine unsaturation test, and ready conversion to cholesteryl aniline on treatment with aniline. Both Ⅰ_a and Ⅱ_a when reacted with p-nitrobenzoyl chloride, were easily converted to the corresponding N, O-di-(p-nitrobenzoyl) derivatives, which showed maxima at 1730—1720 cm^-1 and 1640 cm^-1 in the infrared region, characteristic for the ester C=O and amide C=O groups respectively. Furthermore, neither Ⅰ_b nor Ⅱ_b gave cholesteryl aniline on treatment with aniline, so both Ⅰ and Ⅱ must be C₃-substituted 2'-hydroxyethylamino derivatives of △⁵-cholestene, but differing in configuration. By the difference in the rotatory power,Ⅰ and Ⅱ are assigned as 3 β-and 3 α-orientations respectively, according to Bernstein's rule. Ia, when treated with thionyl chloride, gave 3 β-(2'-chloroethylamino)-△⁵-cholestene hydrochloride (Ⅳ), which on reacting with thiourea, yielded 3β-(2'-isothiuroniumethylamino)-△⁵-cholestene chloride hydrochloride (Ⅴ). Ⅴ gave 3β-(2'-mercaptoethylamino)△⁵-cholestene hydrochloride (Ⅵ) on alkaline hydrolysis followed by acidification with hydrochloric acid. Ⅵ showed positive iodine-azide test and absorption band at 2510 cm^-1 in the infrared region, both characteristic for sulfhydryl group. Thiocholesterol, on treatment with β-bromoethylamine in ethanolic sodium ethoxide solution, gave 3β-(2'-aminoethylmercapto)-△⁵-cholestene (Ⅶ), which was isolated in the form of nicotinic acid salt. Similarly, 3β-(3'-pthalimidopropylmercapto)-△⁵-cholestene (Ⅷ) was obtained by the reaction of thiocholesterol with γ-phthalimidopropylbromide in ethanolic sodium ethoxide solution. Thiocholesterol, when treated with 3, 4, 5-trimethoxybenzoyl chloride gave 3β-(3', 4', 5'-trimethoxybenzoylmercapto)-△⁵-cholestene (Ⅸ).