Ingenol is a highly complex, plant derived compound. Scientists at the Scripps Research institute (TSRI) have achieved the first efficient chemical synthesis of the compound.
“I think that most organic chemists had considered ingenol beyond the reach of scalable chemical synthesis,” said TSRI Professor Phil S. Baran.
Ingenol and its derivatives, well known cancer fighting agents, are found in the widely distributed Euphorbia genus of plant, whose milky sap has long been used in traditional medicine to treat skin lesions. Ingenol mebutate, extracted from the common “petty spurge” plant (E. peplus), was recently approved by the U.S. FDA, European Medicines Agency, Medicines Australia and Health Canada to treat actinic keratosis, a common type of precancerous lesion associated with cumulative sun exposure. Formulated and marketed as Picato®, the drug has also shown effects in models and in early trials of non-melanoma skin cancers.
Studies have shown that ingenol mebutate, which is applied topically, can treat precancerous skin cells unusually rapidly, while sparing healthy skin cells. The treatment has a direct cancer-cell-killing effect, and also induces an inflammatory reaction. Researchers suspect that derivatives of ingenol mebutate may be useful in treating other types of cancer, if they can be delivered properly.
Until now, it was debatable whether such derivatives could ever be synthesized. Some prominent researchers have suggested recently that the efficient chemical synthesis of structurally unusual “terpenoid” compounds such as ingenol is an unreachable goal — and that drug developers should seek biotechnology solutions instead.
1.Lars Jørgensen, Steven J. McKerrall, Christian A. Kuttruff, Felix Ungeheuer, Jakob Felding, and Phil S. Baran. 14-step synthesis of ( )-ingenol from ( )-3-carene. Science, 1 August 2013 DOI: 10.1126/science.1241606