Strategic Redox Relay Enables A Scalable Synthesis of Ouabagenin, A Bioactive Cardenolide

• Autores: Hans Renata, Qianghui Zhou, Phil S. Baran
• Localización: Science, ISSN 0036-8075, Vol. 339, Nº 6115, 2013, págs. 60-63
• Idioma: inglés
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• Resumen

  • Here, we report on a scalable route to the polyhydroxylated steroid ouabagenin with an unusual take on the age-old practice of steroid semisynthesis. The incorporation of both redox and stereochemical relays during the design of this synthesis resulted in efficient access to more than 500 milligrams of a key precursor toward ouabagenin—and ultimately ouabagenin itself—and the discovery of innovative methods for carbon-hydrogen (C-H) and carbon-carbon activation and carbon-oxygen bond homolysis. Given the medicinal relevance of the cardenolides in the treatment of congestive heart failure, a variety of ouabagenin analogs could potentially be generated from the key intermediate as a means of addressing the narrow therapeutic index of these molecules. This synthesis also showcases an approach to bypass the historically challenging problem of selective C-H oxidation of saturated carbon centers in a controlled fashion.