title: Total synthesis and biological evaluation of the natural product (-)-cyclonerodiol, a new inhibitor of IL-4 signaling.
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.
authors.affiliation: Institute of Organic Chemistry, University of Mainz, Duesbergweg 10-14, D-55128 Mainz, Germany. opatz@uni-mainz.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Langhanki
authors.forename: Kristina
authors.initials: K
authors.lastname: Rudolph
authors.forename: Gerhard
authors.initials: G
authors.lastname: Erkel
authors.forename: Till
authors.initials: T
authors.lastname: Opatz
mesh_terms: D000080462:Acyclic Monoterpenes; D018926:Anti-Allergic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001249:Asthma / Q000188:drug therapy; D002460:Cell Line; D003500:Cyclization; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000276:immunology; D039821:Monoterpenes / Q000737:chemistry; D050800:STAT6 Transcription Factor / Q000276:immunology; D012717:Sesquiterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000080462:Acyclic Monoterpenes; D018926:Anti-Allergic Agents; D039821:Monoterpenes; D050800:STAT6 Transcription Factor; D012717:Sesquiterpenes; D015847:Interleukin-4; C000539:cyclonerodiol; C018584:linalool