Scientists invent new methods to develop complex natural steroids
12 January 2013
Scientists at The Scripps Research Institute (TSRI) have achieved a feat in synthetic chemistry by inventing a scalable method to make complex natural compounds known as ''polyhydroxylated steroids.''
These compounds, used in heart-failure medications and other drugs, have been notoriously problematic to synthesise in the laboratory.
The researchers demonstrated the new strategy by synthesising ouabagenin (pronounced wa-bah-jenn-in), a close chemical cousin of ouabain, which Somali tribes once used as a potent poison on the tips of their arrows but was later developed as a treatment for congestive heart failure.
This achievement, reported in the 4 January 2012 issue of Science, points the way to a scalable formation and modification of a variety of useful compounds that had been obtainable in significant quantities only from plants or animals.
''Previous synthetic routes to these compounds required so many steps as to be impractical on a large scale,'' says Phil S Baran, a professor and a member of the Skaggs Institute for Chemical Biology at TSRI, ''but we were able to come up with a completely new strategy.''
Looking for answers
The Baran laboratory has a long-standing interest in the practical and scalable synthesis of complex natural products. The group's latest achievement was stimulated by a request from a Denmark-based drug company, LEO Pharma, whose chemists sought an efficient way to make complex, bioactive steroids.