Synthetic Studies Toward Rubradirin

Abstract

The decorated and glycosylated ansamycin rubradirin exhibits potent antimicrobial activity and a dual mode of action. Herein, we report our efforts toward its synthesis, leading to a successful synthesis of three of its four fragments, i.e., the pyridine, coumarin, and carbohydrate moieties. While the central dihydroxypyridine fragment was successfully coupled to the coumarin part, we encountered significant challenges in its glycosylation. For rubransarol, the ansamycin core fragment of rubradirin, synthetic protocols were established for the construction of the tricyclic core as well as the full-length ansa-chain. Finally, attachment of the ansa-chain was demonstrated at both anchor points of the rubransarol core, leading to the assembly of the 19-carbon skeleton of rubransarol.