亮菌甲素合成方法的研究
STUDIES ON THE SYNTHESIS ARMILLARISIN A
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摘要: 亮菌甲素为治疗急性胆道感染的一个新的有效药物。为了改进其合成方法和提高收率,以期能过渡到工业生产,采用碘化钾为催化剂,以氯化苄使3,5-二羟基苯甲酸甲酯苄醚化得(Ⅳ),反应时间缩短,收率达80~90%,然后用四氢硼钾和氯化锂还原,5%pd/c接触氢解去苄基得定量产率的(Ⅴ),原合成路线中甲酰化与缩合改为(Ⅴ)与α-乙氧亚甲基乙酰乙酸乙酯在醇钠存在下直接缩合而得(Ⅵ),总收率达40%左右(以苯甲酸计算)。Abstract: A practical method for the preparation of Armillarisin A is described. The key intermediate, 3, 5-dihydroxyphenylcarbinol, was prepared through etherification of methyl 3, 5-dihydroxybenzoate with benzylchloride in the presence of potassium carbonate and catalytic amount of potassium iodide, and then reduction of the etherified product by potassium boronhydride-Lithium chloride, and finally debenzylation by hydrogenation over 5% Pd/C, the yield of this step being 71%.Armillarisin A was prepared through the direct condensation of 3, 5-dihydroxyphenylcarbinol with ethyl ethoxymethylene acetylacetate in the presence of sodium ethoxide, the yield being 60~70%. The overall yield was 40% (on the basis of benzoic acid).
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