Total Synthesis and Biological Evaluation of the Anti-Inflammatory (13 R ,14 S ,15 R )-13-Hydroxy-14-deoxyoxacyclododecindione.

The first total synthesis of the natural product (13 R ,14 S ,15 R )-13-hydroxy-14-deoxyoxacyclododecindione, which was isolated in 2018 as a member of the oxacyclododecindione family, is reported. A synthetic strategy through intramolecular Friedel-Crafts acylation combined with the stereoselective synthesis of a new triol key fragment allowed the preparation of the macrolactone. Due to mismatching physical data of the synthetic product, a revision of the configuration of the natural product isolated in 2018 is required. Light-induced E / Z -isomerism of the macrolactone backbone is described for the first time in the class of oxacyclododecindione-type macrolactones. The hydroxylated macrolactone prepared herein was found to show highly promising IC 50 values in biological assays addressing the inhibition of inflammatory responses.