Solid phase methods have been central to the chemical synthesis of peptides, yet al iquid phase method would arguably be more appropriate withm odern synthetic chemistry approaches to fine-tune the molecular structures of peptides. Herein, we describe as imple and rational design fort he synthesis of 2,5-substituted hydrophobic benzyl alcohol (HBA) as an ew soluble tag for liquid phase peptides ynthesis. This tag allows the use of both 9-fluorenylmethoxycarbonyl (Fmoc) and HF-free tertbutoxycarbonyl (Boc) methods. The HBA-tagged peptides can be detected both colorimetrically and fluorometrically, enabling their quantitative assay.T he Boc method is compatible with the HBA tag because it is mildly acid resistant, whereas commonly used acidic global deprotection conditions lead to the simultaneousc leavage of the side chain protecting groups and the HBA tag. The HBA tag was successfully appliedt ot he synthesis of the angiotensin III selective antagonistp eptide.Scheme1.Comparison of Fmocand Boc methodscurrently used for the chemical synthesis of peptides.