Total synthesis of 14β-hydroxy-8α, 9α- and 14β-hydroxy-8α, 9β-estradiols

1. The reduction of the 17-keto group in ketol (II) with LiAlH4 gives predominantly the 17α-diol (VI), whereas the similar reduction with NaBH4 leads to a mixture of the 17β- and 17α-diols (VII) and (VI) in a 5∶4 ratio. 2. The catalytic hydrogenation of diols (VI) and (VII) proceeds stereospecificalty to give the corresponding 3-methyl ethers of the 8α, 9α-estra-3, 14β, 17-triols (VIII) and (X). 3. The reduction of the Δ9(11) double bond in diols (VI) and (VII) with sodium in liquid NH3 proceeds in a strictly stereospecific manner to give the corresponding 3-methyl ethers of the 8α, 9β-estra-3, 14β, 17-triols (IX) and (XI). 4. The formation of an intramolecular hydrogen bond in the series of 14β, 17β-cis-diols (X) and (XI) depends on the configuration of the hydrogen at C-9.