Full stereochemical determination of ajudazols A and B by bioinformatics gene cluster analysis and total synthesis of ajudazol B by an asymmetric ortholithiation strategy

• Verfasst von: Essig, Sebastian [VerfasserIn]
• Verfasst von: Bretzke, Sebastian [VerfasserIn]
• Titel: Full stereochemical determination of ajudazols A and B by bioinformatics gene cluster analysis and total synthesis of ajudazol B by an asymmetric ortholithiation strategy
• Verf.angabe: Sebastian Essig, Sebastian Bretzke, Rolf Müller, and Dirk Menche
• E-Jahr: 2012
• Jahr: 28 November 2012
• Umfang: 4 S.
• Fussnoten: Gesehen am 29.11.2018
• Titel Quelle: Enthalten in: American Chemical SocietyJournal of the American Chemical Society
• Ort Quelle: Washington, DC : ACS Publications, 1879
• Jahr Quelle: 2012
• Band/Heft Quelle: 134(2012), 47, Seite 19362-19365
• ISSN Quelle: 1520-5126
• DOI: doi:10.1021/ja309685n
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1584651466

Abstract

The stereochemical determination of the potent respiratory chain inhibitors ajudazols A and B and the total synthesis of ajudazol B are reported. Configurational assignment was exclusively based on biosynthetic gene cluster analysis of both ketoreductase domains for hydroxyl-bearing stereocenters and one of the first predictive enoylreductase alignments for methyl-bearing stereocenters. The expedient total synthesis resulting in unambiguous proof of the predicted stereochemistry involves a short stereoselective approach to the challenging isochromanone stereotriad by an innovative asymmetric ortholithiation strategy, a modular oxazole formation, and a late-stage Z,Z-selective Suzuki coupling.