title: A surprising switch in absolute configuration of anti-inflammatory macrolactones.
abstract: Oxacyclododecindione-type macrolactones exhibit highly potent anti-inflammatory activities even at nanomolar concentration. After the determination of the relative configuration of the stereocenters at C14 and C15 by total synthesis of 4-dechloro-14-deoxyoxacyclododecindione and 14-deoxyoxacyclododecindione, the absolute configuration has now been assigned by X-ray crystallography. Surprisingly, the absolute configuration is (14S,15R) which differs for C15 from that of the well-known derivatives of (S)-curvularin. The biological activities of both enantiomers of 14-deoxyoxacyclododecindione, obtained by racemic synthesis and optical resolution, were investigated and the ring conformation of the natural product was compared to that of (S)-curvularin and (R)-dehydrocurvularin.
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. opatz@uni-mainz.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Tauber
authors.affiliation: Department of Molecular Biotechnology & Systems Biology, University of Kaiserslautern, Erwin-Schrödinger Str. 70, Building 70, 67663 Kaiserslautern, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Rohr
authors.affiliation: Department of Molecular Biotechnology & Systems Biology, University of Kaiserslautern, Erwin-Schrödinger Str. 70, Building 70, 67663 Kaiserslautern, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Walter
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. opatz@uni-mainz.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Schollmeyer
authors.affiliation: R&D LGCR/Chemistry FF, Sanofi GmbH, D-65926 Frankfurt am Main, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Rahn-Hotze
authors.affiliation: Department of Molecular Biotechnology & Systems Biology, University of Kaiserslautern, Erwin-Schrödinger Str. 70, Building 70, 67663 Kaiserslautern, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Erkel
authors.affiliation: Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany. opatz@uni-mainz.de.
authors.forename: Till
authors.initials: T
authors.lastname: Opatz
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology; D018360:Crystallography, X-Ray; D056945:Hep G2 Cells; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
chemical_list: D000893:Anti-Inflammatory Agents; D047028:Macrocyclic Compounds; C532274:oxacyclododecindione