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An Efficient Large-Scale Synthesis of EDP-420, a First-in-Class Bridged Bicyclic Macrolide (BBM) Antibiotic Drug Candidate
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2010
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Combinatorial ChemistryEngineeringAntibiotic AdjuvantOrganic ChemistryDrug ResistanceMedicinal ChemistryDiversity Oriented SynthesisOxime ReductionBridge Oxime FormationDiversity-oriented SynthesisCost-effective SynthesisNatural Product SynthesisPharmacologyBiomolecular EngineeringEfficient Large-scale SynthesisNatural SciencesSynthetic BiologyAntibiotic Drug CandidateSynthetic ChemistryDrug Discovery
A multistep, practical, and cost-effective synthesis of novel bridged bicyclic macrolide drug candidate EDP-420 (1) is described. Starting from inexpensive and commercially available erythromycin A 9-oxime, the current chemical process involves a series of transformations: triacetylation, Pd-catalyzed O,O-bis-allylation (bridge formation), acid-catalyzed sugar cleavage, oxime reduction, acetylation, Os-catalyzed bridge olefin oxidative cleavage, Corey−Kim oxidation, bridge oxime formation, deprotection, and final purification. Multikilogram quantities have been synthesized.