6533b853fe1ef96bd12ad73d

RESEARCH PRODUCT

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

Jens LanghankiTill OpatzGerhard ErkelKristina Rudolph

subject

Acyclic MonoterpenesSesquiterpeneBiochemistryRadical cyclizationCell Linechemistry.chemical_compoundAnti-Allergic AgentsHumansPhysical and Theoretical ChemistryIC50Interleukin 4STAT6Natural productOrganic ChemistryTotal synthesisAsthmachemistryBiochemistryCyclizationImmunologyMonoterpenesInterleukin-4Signal transductionSTAT6 Transcription FactorSesquiterpenesSignal Transduction

description

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.

yearjournalcountryeditionlanguage
2014-10-29Org. Biomol. Chem.
https://doi.org/10.1039/c4ob02021a