Development of a Concise Synthesis of Ouabagenin and Hydroxylated Corticosteroid Analogues

The natural product ouabagenin is a complex cardiotonic steroid with a highly oxygenated skeleton. This full account describes the development of a concise synthesis of ouabagenin, including the evolution of synthetic strategy to access hydroxylation at the C19 position of a steroid skeleton. In addition, approaches to install the requisite butenolide moiety at the C17 position are discussed. Lastly, methodology developed in this synthesis has been applied in the generation of novel analogues of corticosteroid drugs bearing a hydroxyl group at the C19 position. The term “cardiac glycosides”often used interchangeably with “cardiotonic steroids”refers to a class of steroidal natural products exhibiting positive inotropic activity.1 These mole-cules possess the capacity to increase the cardiac output