Solid‐Phase Synthesis of Aza‐Kahalalide F Analogues: (2R,3R)‐2‐Amino‐3‐azidobutanoic Acid as Precursor of the Aza‐Threonine

Abstract

AbstractThe solid‐phase synthesis of six novel analogues of Kahalalide F (KF), a natural product currently undergoing Phase II clinical trials, is reported. In all these compounds, amides were used as isosteres for the depsi bond. For two of these compounds, we performed an efficient synthesis of N‐Fmoc‐protected (2R,3R)‐2‐amino‐3‐azidobutanoic acid, precursor of the aza‐threonine. This is the first example of the solid‐phase reduction of an azide group in the preparation of aza‐Thr‐containing peptides in the solid phase.