Actinic Keratosis — New Chemistry for New Drugs
Lowell A. Goldsmith, MD
Remember those exam questions in organic chemistry where you were asked to design the synthesis of a compound starting with a simple organic molecule? Some saw "organic" as a hurdle on the way to biochemistry in medical school; others stayed the course and kept developing new syntheses. A very long and very detailed article in Science (23 August 2013) describes the short and inexpensive synthesis of (+) –ingenol -- the basis of a new FDA-approved compound for treating actinic keratosis (ingenol mebutate). Before, the only source of the molecule was through relatively inefficient procedures starting with Euphorbia peplus. The details of the procedure will interest chemistry aficionados; for me, there were two more general messages:
First: natural compounds -- even those that seem, and are, very complex -- can be synthesized using today’s techniques. (Jorgensen et al describe a 14-step synthesis with an overall yield of 1.2%, which compares favorably with ingenol’s isolation from natural materials.)
Second: as impressive to me was that LEO Pharma supported this research in conjunction with the Department of Chemistry at Scripps, evidence of very creative interactions between industry and academia and an important model for many kinds of research.
This section is for advanced credit.
The official name of Euphorbia peplus is Euphorbia peplus L. The L. means that the ultimate authority, Carolus Linneaeus, named the species. See www.plants.usda.gov for some details and pictures of the plant called the “petty spurge". The plant has other names such as ‘cancer weed’ and ‘radium weed’. The origin of those names, especially the latter,deserves some further documentation since the word “radium” did not exist until 1898. If there are botany namers reading this, their responses are welcomed.