Researchers led by , now at the Free University of Berlin, reported the first total synthesis later that year (2009, DOI: ; C&EN, Nov. 16, 2009, page 40). More than a dozen other englerin A syntheses have since been carried out by chemists.
Since its discovery six years ago, the molecule (–)-englerin A has received a lot of attention from organic chemists and biologists. The natural product has a complex architecture that makes it a challenging synthetic target, and its ability to kill kidney cancer cells selectively makes it a promising drug lead.
The program initiated by basic research in the new field of gold catalysis led to the total synthesis of a biologically relevant molecule, opening the doorway to a practical solution for the synthesis of structurally simplified analogues, which were developed in the CSOL (Catalyst Selection and Optimization Laboratory) unit at ICIQ. This Technology Development Unit is oriented the valorization of research results developed at ICIQ in order to bridge the gap between research results and their application in industry. The biological studies have been carried out in the US National Cancer Institute (National Institute of Health, USA) by Prof. Beutler and collaborators.
Taking the previous total synthesis of the natural product as starting point, Echavarren's group has synthetized a set of analogues with great structural diversity. An important point to note is that the original synthesis has been scaled-up to the multigram scale. "We have developed potent anticancer compounds inspired on the structure of englerin as a final result of curiosity-driven research in gold chemistry" -says Prof. Echavarren.
In 2010 the research group of Prof. Echavarren achieved the total synthesis of (-)-Englerin A starting from inexpensive geraniol and using as the key transformation a gold-catalyzed cycloaddition invented by his group. The synthesis was efficient and easily scalable and, what is more important, the intermediate obtained after the gold-catalyzed cycloaddition opened the way for the synthesis of new and useful derivatives.
IMAGE: The research group of professor Echavarren at ICIQ has designed and synthesized a series of analogues of (-)-Englerin A that are highly selective and effective in the growth-inhibition of renal...
The research group of at ICIQ has designed and synthetized a series of analogues of (-)-Englerin A that are highly selective and effective in the growth-inhibition of renal cancer cells.
The molecule (-)-Englerin A was isolated in 2009 from the bark of the east African plant Phyllanthus engleri by scientists at the US National Cancer Institute, and has received a lot of attention because of its ability to kill kidney cancer cells selectively. Kidney cancer is often treated surgically and responds poorly to existing drugs, which can have serious side effects. So, new drugs based on (-)-englerin A could help improve outcomes for patients. Several total syntheses have been reported to date and two distinct mechanisms for Englerin A's anticancer activity have been proposed.