Despite extensive years of research, the direct oxidation of the 7,8-double bond of opioids has so far received little attention and knowledge about the effects of this modification on activity at the different opioid receptors is scarce. We herein report that potassium permanganate supported on iron(II) sulfate heptahydrate can be used as a convenient oxidant in the one-step, heterogeneous conversion of Δ^7,8-opioids to the corresponding 7β-hydroxy-8-ketones. Details of the reaction mechanism are given and the effects of the substituent at position 6 of several opioids on the reaction outcome is discussed. The opioid hydroxy ketones prepared are antagonists at the mu- and delta-opioid receptors. Docking simulations and detailed structure-activity analysis revealed that the presence of the 7β-hydroxy-8-ketone functionality in the prepared compounds can be used to gain activity towards the delta opioid receptor. The 7β-hydroxy-8-ketones prepared with this method can also be regarded as versatile intermediates for the synthesis of other opioids of interest.

尽管进行了多年的研究，到目前为止，阿片类药物的7,8-双键的直接氧化一直很少受到关注，并且关于这种修饰对不同阿片类药物受体活性的影响的知识很少。本文我们报告支撑在铁高锰酸钾（II）七水硫酸可以用作在一工序的方便氧化剂，异构Δ转换^7,8--阿片类药物对应的7β-羟基-8-酮。给出了详细的反应机理，并讨论了几种阿片类药物第6位的取代基对反应结果的影响。所制备的阿片样物质羟基酮是μ阿片和δ阿片样物质受体的拮抗剂。对接模拟和详细的结构活性分析表明，所制备化合物中7β-羟基-8-酮官能团的存在可用于获得针对δ阿片受体的活性。用这种方法制备的7β-羟基-8-酮也可以被认为是合成其他目的阿片类药物的通用中间体。