Asymmetric Total Synthesis of the Naturally Occurring Antibiotic Anthracimycin
Emma K. Davison, Jared L. Freeman, Wanli Zhang, William M. Wuest, Daniel P. Furkert, Margaret A. Brimble
Abstract
The first total synthesis of the potent antibiotic anthracimycin was achieved in 20 steps. The synthesis features an intramolecular Diels–Alder reaction to forge the trans-decalin moiety, and an unprecedented aldol reaction using a complex β-ketoester to provide the tricarbonyl motif. A Stork–Zhao olefination and Grubbs ring closing metathesis delivered the E/Z-diene and forged the macrocycle. The C2 configuration was set with a base-mediated epimerization, providing access to (−)-anthracimycin.
Topics & Concepts
ChemistryTotal synthesisAldol reactionIntramolecular forceStereochemistryMoietyMetathesisEpimerPolyketideDieneDecalinGrubbs' catalystCombinatorial chemistryOrganic chemistryCatalysisBiosynthesisPolymerizationPolymerNatural rubberEnzymeMicrobial Natural Products and BiosynthesisSynthetic Organic Chemistry MethodsAsymmetric Synthesis and Catalysis