Joannou G E, Reeder A Y
Department of Metabolic Mass Spectrometry, Royal Prince Alfred Hospital, Camperdown, New South Wales, Sydney, Australia.
Steroids. 1996 Jan;61(1):11-7. doi: 10.1016/0039-128x(95)00169-q.
We report the synthesis of 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20- one (1) from 3 beta,15 beta-dihydroxy-5,16-pregnadien-20-one (11) in 7 steps using boronate derivatives as a means of protecting the 17,20-glycol side-chain of steroid intermediates. 16 alpha,17 alpha-Epoxy-3 beta,15 beta-dihydroxy-5- pregnen-20-one (12), an intermediate in the synthesis was prepared by epoxidation of 11 using a mixture of sodium hydroxide and hydrogen peroxide. Reduction of 12 with lithium aluminium hydride gave the two isomers of 5-pregnene-3 beta, 15 beta,17 alpha,20 (S+R)-tetrol (13a and 13b) which on subsequent reaction with n-butyl boronic acid gave 5-pregnene-3 beta,15 beta,17 alpha, 20(S+R)-tetrol 17 alpha,20-butyl boronate (15a and 15b). Acetylation with acetic anhydride and pyridine yielded 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha,20(S+R)-diol 17 alpha,20(S+R)-butyl boronate (15c and 15d). Oxidative cleavage of the boronic ester using sodium hydroxide and hydrogen peroxide gave 3 beta,15 beta-diacetoxy-5-pregnene-17 alpha,20(S+R)-diol (13c and 13d). After isolation of these latter two products, dibromide protection of the C-5,6 olefin of 13d and oxidation with N-bromosuccinimide gave 3 beta,15 beta-diacetoxy-17 alpha-hydroxy-5-pregnen-20-one (16) which on deacetylation gave in good yield (35%) the desired product 3 beta,15 beta,17 alpha-trihydroxy-5-pregnen-20-one (1) in an overall yield of 24% from 11.
我们报道了以硼酸酯衍生物作为保护甾体中间体17,20 -二醇侧链的手段，从3β,15β -二羟基-5,16 -孕二烯-20 -酮（11）经7步合成3β,15β,17α -三羟基-5 -孕烯-20 -酮（1）的过程。合成中间体16α,17α -环氧-3β,15β -二羟基-5 -孕烯-20 -酮（12）是通过用氢氧化钠和过氧化氢的混合物对11进行环氧化反应制备的。用氢化铝锂还原12得到5 -孕烯-3β,15β,17α,20（S + R）-四醇（13a和13b）的两种异构体，其随后与正丁基硼酸反应得到5 -孕烯-3β,15β,17α,20（S + R）-四醇17α,20 -丁基硼酸酯（15a和15b）。用乙酸酐和吡啶进行乙酰化反应得到3β,15β -二乙酰氧基-5 -孕烯-17α,20（S + R）-二醇17α,20（S + R）-丁基硼酸酯（15c和15d）。用氢氧化钠和过氧化氢对硼酸酯进行氧化裂解得到3β,15β -二乙酰氧基-5 -孕烯-17α,20（S + R）-二醇（13c和13d）。分离出后两种产物后，对13d的C - 5,6烯烃进行二溴化物保护并用N -溴代琥珀酰亚胺氧化得到3β,15β -二乙酰氧基-17α -羟基-5 -孕烯-20 -酮（16），其脱乙酰化后以良好的产率（35%）得到所需产物3β,15β,17α -三羟基-5 -孕烯-20 -酮（1），以11为原料的总产率为24%。
