A short efficient synthesis of 16-oxygenated estratriene 3-sulfates.
A novel synthesis of sodium 17-oxo-16 alpha-hydroxy-1,3,5(10)-estratrien-3-yl sulfate (4), sodium 16 alpha, 16 beta-dihydroxy-1,3,5(10)-estratrien-3-yl sulfate (5) and sodium 16-oxo-17 beta-hydroxy-1,3,5(10)-estratrien-3-yl sulfate (6) is described. 16 alpha-Bromo-3-hydroxy-1,3,5(10)-estratrien-17-one (1) was efficiently synthesized in one step with 70-97% yield by bromination of 3-hydroxy-1,3,5(10)-estratrien-17-one with cupric bromide. 3,16 alpha-Dihydroxy-1,3,5(10)-estratrien-17-one (3) was quantitatively obtained by controlled stereospecific hydrolysis of the bromoketone 1 with sodium hydroxide in aqueous pyridine. The bromoketone 1 was converted to the 16 alpha-hydroxy-17-ketone 3-sulfate 4 by sulfation with chlorosulfonic acid in pyridine and a subsequent controlled hydrolysis in a high yield without formation of the other ketols. Treatment of the sulfate 4 with sodium borohydride have the triol sulfate 5. The sulfate 4 was also rearranged to the 17 beta-hydroxy-16-ketone 6 with sodium hydroxide in water in a quantitative yield.
D004958:Estradiol / Q000031:analogs & derivatives / Q000138:chemical synthesis; D004964:Estriol / Q000031:analogs & derivatives / Q000138:chemical synthesis; D004966:Estrogens, Conjugated (USP) / Q000138:chemical synthesis*; D004970:Estrone / Q000031:analogs & derivatives / Q000138:chemical synthesis; D006894:Hydroxyestrones / Q000138:chemical synthesis
C024354:16-hydroxyestrone 3-sulfate; D004966:Estrogens, Conjugated (USP); D006894:Hydroxyestrones; C001808:16-oxoestradiol 3-sulfate; D004970:Estrone; C027974:estriol 3-sulfate; D004958:Estradiol; C020523:16-bromoestrone; D004964:Estriol