Numazawa M, Yoshimura A
Tohoku Pharmaceutical University, Sendai, Japan.
Chem Pharm Bull (Tokyo). 2000 Sep;48(9):1359-62. doi: 10.1248/cpb.48.1359.
4Beta,5beta-epoxy derivatives of 16alpha-hydroxyandrostenedione (2), one of the natural substrates for aromatase, and its 19-oxygenated compounds 4 and 5 were synthesized as mechanistic and catalytic probes for the enzyme reaction. Treatment of 16alpha-bromoandrostenedione (13) or its 19-hydroxy analog 19 which was prepared from 3beta-hydroxy-19-(tert-butyldimethylsiloxy)androst-5-en-17-one (16) in three steps, with H2O2 and NaOH followed by controlled alkaline hydrolysis with NaOH in aqueous pyridine stereospecifically yielded 4beta,5beta-epoxy-16alpha-ol 15 or 4beta,5beta-epoxy-16alpha,19-diol 22, respectively. Oxidation of 16beta-bromo-4beta,5beta-epoxy-19-ol 21 with pyridinium dichromate followed by controlled alkaline hydrolysis produced 4beta,5beta-epoxy-16alpha-hydroxy-19-al 24.
16α-羟基雄烯二酮（2）的4β,5β-环氧衍生物，芳香化酶的天然底物之一，及其19-氧化化合物4和5被合成为该酶反应的机理和催化探针。由3β-羟基-19-（叔丁基二甲基硅氧基）雄甾-5-烯-17-酮（16）分三步制备的16α-溴代雄烯二酮（13）或其19-羟基类似物19，先用H2O2和NaOH处理，然后在吡啶水溶液中用NaOH进行受控碱性水解，分别立体定向地生成4β,5β-环氧-16α-醇15或4β,5β-环氧-16α,19-二醇22。用重铬酸吡啶鎓氧化16β-溴-4β,5β-环氧-19-醇21，然后进行受控碱性水解，得到4β,5β-环氧-16α-羟基-19-醛24。
