The facile preparation of primary and secondary amines via an improved Fukuyama–Mitsunobu procedure. Application to the synthesis of a lung-targeted gene delivery agent

Abstract

An efficient modification of the Fukuyama–Mitsunobu procedure has been developed whereby primary or secondary amines can be synthesized from alkyl alcohols and the corresponding nosyl-protected/activated amine. Most importantly, the use of the DTBAD and diphenylpyridinylphosphine, as Mitsunobu reagents, generates reaction by-products that can be easily removed, providing a remarkably clean product mixture. This improved technique was implemented in the synthesis of a complex lipopeptide designed to target α₉β₁-integrin proteins predominant on upper airway epithelial cells.