title: Strategic redox relay enables a scalable synthesis of ouabagenin, a bioactive cardenolide.
abstract: 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.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Hans
authors.initials: H
authors.lastname: Renata
authors.forename: Qianghui
authors.initials: Q
authors.lastname: Zhou
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D002298:Cardenolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D010042:Ouabain / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D010084:Oxidation-Reduction
chemical_list: D002298:Cardenolides; D010042:Ouabain; C008721:ouabagenin