0000000000400235
AUTHOR
Kristina Rudolph
ChemInform Abstract: Synthetic Approaches to Antiinflammatory Macrolactones of the Oxacyclododecindione Type.
A variety of attempts to synthesize oxacyclododecindione macrolactones through carbonylative ring-closure, intramolecular alkyne hydroacyalation, and Ru-catalyzed double bond isomerization fails.
Synthetic Approaches to Anti-Inflammatory Macrolactones of the Oxacyclododecindione Type
Various synthetic approaches to the oxacyclododecindione-type macrolactones, known for their potent anti-inflammatory activity, are presented. These include an attempted carbonylative ring closure, a hydroacylation route, and an approach by ring-closing metathesis and double bond isomerization, as well as a strategy including ring-closing metathesis/unsaturation. The last route allowed the preparation of a bioactive analogue of the recently described 14-deoxyoxacyclododecindione.
Total synthesis and biological evaluation of the natural product (−)-cyclonerodiol, a new inhibitor of IL-4 signaling
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.