title: Full stereochemical determination of ajudazols A and B by bioinformatics gene cluster analysis and total synthesis of ajudazol B by an asymmetric ortholithiation strategy.
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.
authors.affiliation: Institut für Organische Chemie, Ruprecht-Karls Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Essig
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bretzke
authors.forename: Rolf
authors.initials: R
authors.lastname: Müller
authors.forename: Dirk
authors.initials: D
authors.lastname: Menche
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism; D000595:Amino Acid Sequence; D019295:Computational Biology; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013237:Stereoisomerism
chemical_list: D003374:Coumarins; C485090:ajudazol A; C485091:ajudazol B; D000429:Alcohol Oxidoreductases