A short efficient synthesis of 16-oxygenated estratriene 3-sulfates

Article abstract of DOI:10.1016/0039-128X(81)90054-4

A novel synthesis of sodium 17-oxo-16α-hydroxy-1,3,5(10)-estratrien-3-yl sulfate (4), sodium 16α,17β-dihydroxy-1,3,5(10)-estratrien-3-yl sulfate (5) and sodium 16-oxo-17β-hydroxy-1,3,5(10)-estratrien-3-yl sulfate (6) is described. 16α-Bromo-3-hydroxy-1,3,5(10)-estratrien-17-one (1) was efficiently sythesized in one step with 70-97percent yield by bromination of 3-hydroxy-1,3,5(10)-estratrien-17-one with cupric bromide. 3,16α-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 16α-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 gave the triol sulfate 5.The sulfate 4 was also rearranged to the 17β-hydroxy-16-ketone 6 with sodium hydroxide in water in a quantitative yield.