【药物名称】
化学结构式(Chemical Structure):
参考文献No.726989
标题:Synthesis and evaluation of B-, C-, and d-ring-substituted estradiol carboxylic acid esters as locally active estrogens
作者:Labaree, D.C.; Zhang, J.; Harris, H.A.; O'Connor, C.; Reynolds, T.Y.; Hochberg, R.B.
来源:J Med Chem 2003,46(10),1886
合成路线图解说明:

The known phenolic steroid derivative (I) is protected as the corresponding benzyl ether (II) with benzyl bromide in the presence of K2CO3 and i-Pr2NEt. Subsequent ketal hydrolysis in (II) under acidic conditions furnishes the unsaturated ketone (III). Conjugate addition of NaCN to (III) in aqueous THF at reflux gives the 15-beta-cyano steroid (IV). The keto group of (IV) is then reduced with NaBH4 to yield alcohol (V). Hydrolysis of the nitrile group of (V) with KOH in ethyleneglycol leads to the epimerized 15-alpha-carboxylic acid (VI). The O-benzyl protecting group of (VI) is then removed by catalytic hydrogenolysis to provide phenol (VII). Finally, Fischer esterification of acid (VII) with EtOH and sulfuric acid leads to the title ethyl ester.

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