Journal
SCIENCE
Volume 339, Issue 6115, Pages 59-63Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1230631
Keywords
-
Categories
Funding
- LEO Pharma
- TEVA
- NIH/NCI [CA134785]
- Bristol-Myers Squibb
- Shanghai Institute of Organic Chemistry
Ask authors/readers for more resources
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
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available