Synthesis of the N -Alkoxyguanidinyl Spiroketal Core of Rugonidines A–F

Abstract

Abstract Rugonidines A–F are a family of structurally unique diastereomeric alkaloids characterized by an unprecedented [4.5]-fused N-alkoxyguanidinyl spiroketal ring system. This work reports the first synthesis of this motif via an acid-catalyzed, one-pot tandem deprotection/cyclization cascade of a protected N-hydroxyguanidine intermediate, efficiently forging the target spirocyclic framework in 21% yield over nine steps. X-ray crystallographic analysis unambiguously confirmed structural connectivity, providing the first solid-state characterization of this unusual architecture.