Synthesis of Enantiomerically Pure Isoxazolidine Monomers for the Preparation of β3‐Oligopeptides by Iterative α‐Keto AcidHydroxylamine (KAHA) Ligations

Abstract

AbstractA versatile method for the synthesis of enantiomerically pure isoxazolidine monomers for the synthesis of β3‐oligopeptides via α‐keto acidhydroxylamine (KAHA) ligation is presented. This one‐pot synthetic method utilizes in situ generated nitrones bearing gulose‐derived chiral auxiliaries for the asymmetric 1,3‐dipolar cycloaddition with methyl 2‐methoxyacrylate. The resulting enantiomerically pure isoxazolidine monomers bearing diverse side chains (proteinogenic and non‐proteinogenic) can be synthesized in either configuration (like‐ and unlike‐configured). The scalable and enantioselective synthesis of the isoxazolidine monomers enables the use of the synthesis of β3‐oligopeptides via iterative α‐keto acidhydroxylamine (KAHA) ligation.