DRY OZONATION OF STEROIDS. C-25 FUNCTIONALIZATION OF CHOLESTANE DERIVATIVES
DRY OZONATION OF STEROIDS. C-25 FUNCTIONALIZATION OF CHOLESTANE DERIVATIVES
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类固醇的干臭氧化。
DOI：
10.1002/chin.197943317
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
Y. Mazur
中科院分区：
文献类型：
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作者：
Z. Cohen;Y. Mazur
吸附在干燥硅胶上的底物的臭氧化是将氧引入未活化的叔CH键的简便方法。 1 该方法涉及将底物预吸附在色谱级硅胶上，并在 75 至 45 C 之间的温度下通过臭氧，然后用适当的溶剂洗脱。 CH 键对臭氧的反应性取决于 C 原子的电负性及其空间可用性。作为我们合成 25-羟基胆固醇及其衍生物计划的一部分，我们研究了利用臭氧作为饱和胆固醇衍生物羟基化的试剂，作为先前描述的过乙酸氧化的补充方法。我们已经发表了11·一份关于 1a, 3/3-diacetoxy-6, 7-dibromo-5a-cholestane (11) 干臭氧化的初步报告，该反应导致 C-25 羟基化。在本研究中，我们描述了在 5、6 或 7 位取代的其他饱和胆甾烷衍生物的干臭氧化，这些衍生物作为环 B 双键的保护基团。我们选择胆甾烷-3/3-醇乙酸酯(1)作为模型化合物，将其在78°C下在二氧化硅上臭氧化，导致74%转化为羟基化产物的混合物，从中分离出胆甾烷-3)3, 25-二醇3-乙酸酯(2)，产率8%；其余物质是其他单羟基化和二羟基化产物的混合物。胆甾烷-3/3, 5a-二醇3-乙酸酯(3)在类似条件下臭氧化产生80%的羟基化产物，其中含有11%的25-羟基衍生物4。用吸附在硅胶上的氯化铁处理后，该物质转化为25-羟基胆甾醇乙酸酯(5)。 3 5, 6-二溴化物 6 臭氧化时羟基化产率较高，生成 7（产率 15%，转化率 70%）。使用6, 7-二溴化物8（由已知的cholest-6-en-3）3-醇乙酸酯4通过用二溴碘苯溴化制备）获得了更好的结果，其在65℃下臭氧化得到其25-羟基衍生物9作为唯一的分离产物，转化材料的产率为32%（50%）。该化合物是制备 25-羟基维生素 D3 的便利前体，因为其脱溴化氢可生成相应的维生素原，即 cholesta-5, 7-diene-30, 25-diol (10)。
The ozonation of substrates adsorbed on dry silica gel is a convenient method to introduce oxygen into unactivated tertiary CH bonds. 1 This method involves preadsorption of substrate on chromatographic grade silica gel and passing over it ozone at temperatures between-75 and—45 C, followed by elution with an appropriate solvent. The reactivity of CH bonds toward ozone depends both on the electronegativity of the C atom and on its steric availability. As part of our program to synthesize 25-hydroxycholesterol and its derivatives, we have studied the utilization of ozone as a reagent for the hydroxylation of saturated derivatives of cholesterol as a complimentary method to the previously described2 peracetic acid oxidation. We have already published11· a preliminary report on dry ozonation of la, 3/3-diacetoxy-6, 7-dibromo-5a-cholestane (11), which led to C-25 hydroxylation. In this study, we describe dry ozonation of other saturated cholestane derivatives substi-tuted at positions 5, 6, or 7 which serve as protecting groups for ring B double bonds. We have chosen cholestan-3/3-ol ac-etate (1) as a model compound, which was ozonated on silica at—78 C, resulting in 74% conversion to a mixture of hydroxylated products from which cholestane-3) 3, 25-diol 3-acetate (2) was isolated in 8% yield; the rest of the material was a mixture of other monohydroxylated and dihydroxylated products.Ozonation of cholestane-3/3, 5a-diol 3-acetate (3) under similar conditions resulted in 80% of hydroxylated products, containing 11% of the 25-hydroxy derivative 4. This material was converted to 25-hydroxycholesteryl acetate (5) on treatment with ferric chloride adsorbed on silica gel. 3 The yield of hydroxylation was higher on ozonation of the 5, 6-dibromide 6, leading to 7 (15% yield and 70% conversion). Even better results were achieved with the 6, 7-dibromide 8 (prepared from the known cholest-6-en-3) 3-ol acetate4 by bromination with iodobenzene dibromide), which on ozona-tion at—65 C gave its 25-hydroxyderivative 9 as the only isolated product in 32% yield of the convertedmaterial (50%). This compound is a convenient precursor for the preparation of 25-hydroxyvitamin D3 as its dehydrobromination leads to the respective provitamin, the cholesta-5, 7-diene-30, 25-diol (10).