Joannou G E, Reeder A Y
Department of Metabolic Mass Spectrometry, Royal Prince Alfred Hospital, New South Wales, Sydney Australia.
Steroids. 1996 Jan;61(1):18-21. doi: 10.1016/0039-128x(95)00170-u.
A simple three-step synthetic method is reported on the conversion of delta 4-3-ketosteroids to the corresponding 3 beta-hydroxy-delta 5-steroid analogues. 17 alpha-Hydroxy-4-pregnen-3,20-dione (10a) was used as a model to develop a method for the synthesis of 3 beta, 17 alpha-dihydroxy-5-pregnen-20-one (16). The major problem being the synthesis of 3,17 alpha-diacetoxy-3,5-pregnadien-20-one (14) was solved by acetylating using a mixture of acetic anhydride and perchloric acid. The conversion of 15 beta, 17 alpha-dihydroxy-4-pregnen-3, 20-dione (8), product of Penicillium citrinum fermentation, to the desired 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one (1), is described using a modification of this method. Reaction of 8 with acetic anhydride and perchloric acid in ethyl acetate gave 3,15 beta,17 alpha-triacetoxy-3,5-pregnadien-20-one (17) which on reduction with sodium borohydride gave 5-pregnen-3 beta,15 beta,17 alpha, 20(S + R)-tetrols (18a and 18b); however, reduction of 17 with a mixture of sodium borohydride and potassium bicarbonate gave after basic hydrolysis with methanolic sodium hydroxide the desired product 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one (1) in good yield (54%).
报道了一种将δ4-3-酮甾体转化为相应的3β-羟基-δ5-甾体类似物的简单三步合成方法。以17α-羟基-4-孕烯-3,20-二酮（10a）为模型，开发了一种合成3β,17α-二羟基-5-孕烯-20-酮（16）的方法。合成3,17α-二乙酰氧基-3,5-孕二烯-20-酮（14）的主要问题通过使用乙酸酐和高氯酸的混合物进行乙酰化得以解决。描述了采用该方法的改进，将桔青霉发酵产物15β,17α-二羟基-4-孕烯-3,20-二酮（8）转化为所需的3β,15β,17α-三羟基-5-孕烯-20-酮（1）。8与乙酸酐和高氯酸在乙酸乙酯中反应得到3,15β,17α-三乙酰氧基-3,5-孕二烯-20-酮（17），其用硼氢化钠还原得到5-孕烯-3β,15β,17α,20（S + R）-四醇（18a和18b）；然而，17用硼氢化钠和碳酸氢钾的混合物还原后，用甲醇氢氧化钠进行碱性水解，以良好的产率（54%）得到所需产物3β,15β,17α-三羟基-5-孕烯-20-酮（1）。
