Ingenol belongs to a class of medicinally vital compounds known as terpenes, which are commonly found in antiseptics, expectorants, gastrointestinal drugs, pain relievers and antioxidants.1 Ingenol can be further synthesized to ingenol mutbutate, a gel used to treat actinic keratosis. Actinic keratosis is described as flat, scaly growths caused by too much sun exposure.2 This skin condition affects 250 million people worldwide and is a precursor to cancer.3 The treatment is achieved through cell death of the mutated skin cells through the activation of protein kinase A.4 


Ingenol and ingenol mebutate molecules are represented
Source: Jorgensen, L. et al.
 Ingenol is synthesized from a type of weedy plant known as spurges. Due to low isomerization, extraction of the compound from the plant requires 800kg for 1g of the ingenol product which is not an effective method from commercial production.4  In 2013, Jorgensen et. al.  published a study that gave a more efficient and effective stereocontrolled method. The new synthesis not only produces higher yields, it also cuts the 37-steps into a 14-step two phase route.  It is more cost effective and will help limit the production with the possibility of consumer fees. The authors stated that a 1.2% yield can be obtained which is greater than the previous method.5 This synthesis may open new possibilities to finding natural-drug products that aid in diseases with business and consumer spending in mind.


By Christopher Cheng


Sources:
1.     Wisegeek.com.http://www.wisegeek.com/what-are-the-medical-uses-of-terpenes.htm (accessed Apr 6, 2014)
2.     National Library of Medicine. Medline Plus. http://www.nlm.nih.gov/medlineplus/druginfo/meds/a613008.html  (accessed Apr 6, 2014)
3.     Drahl, C. Chemists Find More Efficient Total Synthesis Route To Ingenol.C&EN.[Online] 2013, 91 , 16. http://cen.acs.org/articles/91/i51/Chemists-Find-Efficient-Total-Synthesis.html (accessed Apr 6, 2014)
4.     A.G.Scientific.http://www.agscientific.com/ingenol.html (accessed Apr 6, 2014)
5.     Jorgensen, L.; McKerrall, S. J.; Kuttruff, C. A.; Ungeheuer, F.; Felding, J.; Baran, P.S. 14-Step Synthesis of (+)-Ingenol from (+)-3-Carene. Science. 2013, 341, 878-882
Peplus or Petty spurge, the plant used for ingenol mutbuate
Source: C&EN