Total Synthesis of Ouabain, a Potent Cardiac Glycoside

描述(由申请人提供)： 心脏苷类天然产物作为药物使用已有数百年的历史。哇巴因是这一阶层的重要成员，他发现现代医学在治疗充血性心力衰竭方面有实用价值，这种疾病每年有数百万人患有。鉴于哇巴因在生物学上的重要性，它已成为化学和生物界感兴趣的目标。一条成功的哇巴因合成路线将有助于类似物的制备，因此可能会发现更有效的药物。 本文提出了一种新颖而简明的哇巴因全合成方法。这种不对称合成结合了pi-allyl Heck反应和收敛的分子间Diels-Alder反应来构建C/D环体系，从而构建了天然产物的完整的甾体骨架。此外，还提出了一种用于合成季碳立体中心的催化对映体pi-烯丙基Heck反应变体的开发。

DESCRIPTION (provided by applicant): Cardiac glycoside natural products have been used as medicinal agents for hundreds of years. Ouabain, an important member of this class, has found utility in modern medicine for the treatment of congestive heart failure, a disease that millions of people suffer from every year. Given ouabain's biological importance, it has become a target of interest to the chemical and biological communities. A successful synthetic route to ouabain will assist in the preparation of analogs and could, therefore, allow for the discovery of more powerful medicines. An original and concise approach for the total synthesis of ouabain is presented herein. This asymmetric synthesis incorporates a pi-allyl Heck reaction to build the C/D ring system and a convergent intermolecular Diels-Alder reaction to construct the full steroidal skeleton of the natural product. The development of a catalytic enantioselective variant of the pi-allyl Heck reaction for the synthesis of quaternary carbon stereocenters is also proposed.