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Chemistry. 2012 Mar 12;18(11):3092-120. doi: 10.1002/chem.201103733. Epub 2012 Feb 22.
The active components from the extracts of Digitalis, cardiotonic steroid glycosides, have been ingested by humans for more than 200 years as a medicinal therapy for heart failure and abnormal heart rhythms. The positive inotropic activity of the cardiotonic steroids that mediates clinically useful physiological effects in patients has been attributed largely to a high affinity inhibitory interaction with the extracellular surface of the membrane-bound sodium pump (Na(+)/K(+)-ATPase). However, previously unrecognized intracellular signaling pathways continue to be uncovered. This Review examines both partial and de novo synthetic approaches to the medicinally important and structurally captivating cardenolide and bufadienolide steroid families, with an emphasis on the stereocontrolled construction of the pharmacophoric aglycone (genin) framework.
从洋地黄属植物、强心苷类糖配基的提取物中提取的活性成分，已被人类作为心力衰竭和异常心律的治疗方法摄入超过 200 年。强心甾类物质的正性肌力活性介导了临床上对患者有益的生理效应，这在很大程度上归因于与膜结合的钠泵（Na(+)/K(+)-ATPase）的细胞外表面的高亲和力抑制相互作用。然而，以前未被识别的细胞内信号通路仍在不断被发现。本综述考察了对具有医学重要性和结构吸引力的卡烯内酯和蟾蜍内酯甾体家族的部分和从头合成方法，重点是对药效团苷元（配基）框架的立体控制构建。
