ORGN 725 |
| The cardiotonic steroid ouabain (1) is a small and complex molecule that has been used clinically for the treatment of congestive heart failure and has been found to exhibit cytotoxic activity against human leukemia cells. The structural architecture of ouabain, as well as most cardenolides, differs from common steroids in several aspects. The AB and CD rings of ouabain are cis fused rather than trans fused. The steroid nucleus is decorated with a tertiary hydroxyl group at C14, the methyl group of C19 is hydroxylated, and a butenolide substituent at C17. The unique stereochemistry along with the high degree of oxygenation makes ouabain a challenging synthetic target. The steroid core will arise from an inverse-electron demand Diels-Alder reaction to establish the cis CD ring junctions. The A ring will be developed from Robinson annulation onto the BCD tricycle. Furthermore, the synthetic strategy will allow access to other cardiotonic steroids, such as rhodexin A (2). This presentation will focus on the construction of the tricyclic BCD ring system and the progress made toward the total synthesis.
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Total Synthesis, Materials, Molecular Recognition, Process R&D, and Physical Organic Chemistry
8:00 PM-10:00 PM, Wednesday, 13 September 2006 Moscone Center -- Hall D, Poster
Division of Organic Chemistry |
