- Novel and Efficient Synthesis of Estriol and its 16-Glucuronide via 2,4,16α-Tribromoestrone
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A novel synthesis of estra-1,3,5(10)-triene-3,16α,17β-triol (5), sodium 3,17β-dihydroxyestra-1,3,5(10)-trien-16α-yl-β-D-glucopyranosuronate (12b) aand sodium 3-hydroxyestra-1,3,5(10)-trien-17β-yl-β-D-glucopyranosuronate (10b) is described. 2,4,16α-Tribromo-3-hydroxyestra-1,3,5(10)-trien-17-one (2a) was efficiently synthesized in one step with quantitative yield by bromination of 3-hydroxyestra-1,3,5(10)-trien-17-one (1) with cupric bromide.Treatment of (2a) with NaOH in aqueous pyridine under the controlled conditions gave the 16α-hydroxy-17-ketone (4a) without ketol rearrangement.The ketol (4a) was converted in quantitative yield into the triol (5) via a sodium borohydride reduction in the presence of palladium chloride.Reaction of (4a) with methyl 1-bromo-1-deoxy-2,3,4-tri-O-acetyl-α-D-glucopyranosuronate using silver carbonate as a catalyst yielded the 16-monoglucuronide acetate methyl ester (11).The reductive removal of the bromines of (11) with sodium borohydride followed by NaOH hydrolysis gave the glucuronide (12b).A direct glucuronidation of 2,4-dibromoestra-1,3,5(10)-triene-3,17β-diol (8) and a subsequent hydrolysis of the 17-glucuronide (9) gave the glucuronide (10b).
- Numazawa, Mitsuteru,Nagaoka, Masao,Tsuji, Masachika,Osawa, Yoshio
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p. 121 - 125
(2007/10/02)
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