Total Synthesis of the Acetyl CoA Carboxylase Inhibitor Soraphen A: Asymmetric Tsuji Reduction Enables Successive Olefin Metathesis
Tabitha T. Schempp, Michael J. Krische
Abstract
The total synthesis of soraphen A, a myxobacterial metabolite and inhibitor of acetyl CoA carboxylase, was completed in 11 steps (longest linear sequence), less than half the steps previously required. Seven metal-catalyzed processes were deployed to unlock step-economy (comprising five asymmetric processes and four C-C bond formations). The present route does not utilize chiral auxiliaries, and four of five C-C bond formations exploit non-premetalated partners. To maximize convergency, an asymmetric Tsuji reduction was developed using a Pd-AntPhos catalyst that allows a metathesis-inactive allylic carbonate to serve as a masked terminal olefin, thereby enabling successive olefin metathesis events.
Topics & Concepts
ChemistryAcetyl-CoA carboxylaseTotal synthesisReduction (mathematics)StereochemistryOlefin metathesisMetathesisOlefin fiberCombinatorial chemistryPyruvate carboxylaseBiochemistryOrganic chemistryEnzymeCatalysisPolymerizationGeometryMathematicsPolymerAsymmetric Hydrogenation and CatalysisSynthetic Organic Chemistry MethodsChemical Synthesis and Analysis