Development of a Novel Redox-Sensitive Protecting Group for Amines Which Utilizes a Facilitated Lactonization Reaction

Article abstract of DOI:10.1021/jo00108a013

Selective protection and deprotection of functional groups are essential components of modern organic and peptide synthesis.To cope with the demand for the synthesis of organic molecules and peptides with increasing complexity, there has been a need to develop novel protecting groups which are readily cleavable under fundamentally different conditions to ensure selective modifications of specified functional groups.This report is focused on the development of a redox-sensitive amine protecting group using a substituted quinone propionic acid (1a).The key feature of this protecting group is that upon reduction of the quinone 1 to the hydroquinone 2, it undergoes a spontaneous lactonization to release the functional group attached to the carboxyl group (HXR).High yields were achieved for both the protection and deprotection reactions, and the reduction conditions required for the deprotection are very mild (Na2S2O4 or electrochemically) and thus very compatible with most functional groups encountered in organic molecules and peptides.