An efficient large-scale synthesis of EDP-420, a first-in-class bridged bicyclic macrolide (BBM) antibiotic drug candidate

Article abstract of DOI:10.1021/op900228u

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.