A Convergent Synthesis of 14-Membered F-O-G Ring Analogs of the Teicoplanin Binding Pocket via Intramolecular SNAr Reaction

Article abstract of DOI:10.1021/jo00125a026

An intramolecular S_NAr reaction for efficient macrocyclization via biaryl ether formation was developed for syntheses of the 14-membered macrocycles 2 and 3 related to F-O-G ring of teicoplanin 1.Chloride as well as fluoride could be used as the leaving group in this reaction.However, the latter was prefered since it required milder conditions.Both ortho and para nitro, fluoro disubstituted aromatic rings were suitable for the macrocyclization reaction with tethered aryl oxides.The nonproteinogenic α-amino acid 23, required for the synthesis of 3, was prepared via an asymmetric Strecker synthesis using (R)-phenylglycinol as a chiral auxiliary.The overall synthetic strategy was convergent, and the cyclization could be performed in the presence of the highly sensitive arylglycine unit without racemization.