Photo‐Triggered Fluorometric Hydrophobic Benzyl Alcohol for Soluble Tag‐Assisted Liquid‐Phase Peptide Synthesis

Abstract

AbstractSolid phase methods have been central to the chemical synthesis of peptides, yet a liquid phase method would arguably be more appropriate with modern synthetic chemistry approaches to fine‐tune the molecular structures of peptides. Herein, we describe a simple and rational design for the synthesis of 2,5‐substituted hydrophobic benzyl alcohol (HBA) as a new soluble tag for liquid phase peptide synthesis. This tag allows the use of both 9‐fluorenylmethoxycarbonyl (Fmoc) and HF‐free tert‐butoxycarbonyl (Boc) methods. The HBA‐tagged peptides can be detected both colorimetrically and fluorometrically, enabling their quantitative assay. The Boc method is compatible with the HBA tag because it is mildly acid resistant, whereas commonly used acidic global deprotection conditions lead to the simultaneous cleavage of the side chain protecting groups and the HBA tag. The HBA tag was successfully applied to the synthesis of the angiotensin III selective antagonist peptide.