Total Synthesis of Ouabain, a Potent Cardiac Glycoside

强效强心苷哇巴因的全合成

• 批准号: 7117756
• 负责人: NEIL K GARG
• 金额: $ 2.82万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-16 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117756
• 关键词: Diels Alder reaction; analog; biological products; cardiac glycosides; chemical synthesis; chemical transfer reaction; drug discovery /isolation; method development; organic chemicals; stereochemistry

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.

描述（由申请人提供）： 强心苷天然产物已被用作药用制剂数百年。哇巴因是这类药物的重要成员，在现代医学中已被用于治疗充血性心力衰竭，这种疾病每年有数百万人患有。由于哇巴因的生物重要性，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制备类似物，因此可以发现更强大的药物。 本文提出了一种新颖、简洁的哇巴因全合成方法。这种不对称合成结合了π-烯丙基Heck反应以构建C/D环系统和会聚的分子间Diels-Alder反应以构建天然产物的完整甾体骨架。还提出了一种催化的对映选择性变体的π-烯丙基赫克反应的季碳立体中心的合成。

项目成果

Total synthesis of (-)-sarain A.

• DOI: 10.1002/anie.200600417
• 发表时间: 2006-04
• 期刊: Angewandte Chemie
• 作者: N. Garg;S. Hiebert;L. Overman