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Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling†
Jens Langhanki,Kristina Rudolph,Gerhard Erkel,Till Opatz
Organic & Biomolecular Chemistry Pub Date : 10/17/2014 00:00:00 , DOI:10.1039/C4OB02021A
Abstract

In a screening program of natural compounds from fungi, the known cyclopentanoid sesquiterpene (−)-cyclonerodiol was identified as a specific inhibitor of the IL-4 induced STAT6 signaling pathway (IC50 = 9.7 μM) which is required for the differentiation of naive CD4 T cells to T helper type 2 (Th2) lymphocytes. As many allergic conditions, including allergic asthma and atopic diseases, are driven by an excessive Th2 response, STAT6 is a promising target for the development of new therapeutics. The compound was synthesized in six steps from (−)-linalool using an epoxide radical cyclization as the key step.

Graphical abstract: Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling
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