Actinic Keratosis — New Chemistry for New Drugs

4 September 2013 by Lowell Goldsmith - JID Jottings, posted in Uncategorized

image from the public domain accessed from www.plants.usda.gov

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.

 

REFERENCES:

Jorgensen L, McKerrall SJ, Kuttruff CA (2013) 14-Step Synthesis of (+)-Ingenol from (+)-3-Carene. Science 341:878-882

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