Tauber Johannes, Rohr Markus, Walter Thorsten, Schollmeyer Dieter, Rahn-Hotze Karin, Erkel Gerhard, Opatz Till
Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128 Mainz, Germany.
Department of Molecular Biotechnology & Systems Biology, University of Kaiserslautern, Erwin-Schrödinger Str. 70, Building 70, 67663 Kaiserslautern, Germany.
Org Biomol Chem. 2016 Apr 12;14(15):3695-8. doi: 10.1039/c6ob00430j.
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.
氧杂环十二烷二酮型大环内酯即使在纳摩尔浓度下也表现出高效的抗炎活性。通过全合成4-脱氯-14-脱氧氧杂环十二烷二酮和14-脱氧氧杂环十二烷二酮确定了C14和C15处立体中心的相对构型后，现在已通过X射线晶体学确定了绝对构型。令人惊讶的是，绝对构型为(14S,15R)，其中C15的构型与著名的(S)-弯孢菌素衍生物不同。研究了通过外消旋合成和光学拆分得到的14-脱氧氧杂环十二烷二酮两种对映体的生物活性，并将天然产物的环构象与(S)-弯孢菌素和(R)-脱氢弯孢菌素的环构象进行了比较。
