We have reported AJIPHASE® technology^1-2  , a novel methodology of liquid-phase peptide synthesis (LPPS), by using anchor support compounds bearing long aliphatic chain as a protecting group at C-terminal. This retains strong points of both synthetic approaches: solid-phase peptide synthesis (SPPS) and LPPS. We developed soluble anchor support compounds, possessing an alcohol/amine scaffold substituted by a long alchoxy chain. These anchor compounds are applicable to the Fmoc chemistry to prepare free form peptides, peptide amides and protected peptide acids. The usefulness of the AJIPHASE® method with anchor support compounds which facilitate dissolution and precipitation for LPSS was demonstrated by the successful synthesis of various peptides in high yield and high purity even by large scale.

Additionally, we tackled further development to improve efficiency. AJIPHASE® method using precipitation has still had room for improvement in especially complicated work-up for isolation. In these studies, one-pot synthesis without isolation can be realized in peptide elongation by phase separation method using new type of anchor support compound having branched chains and using new reagents for Fmoc deprotection step. We confirmed that the synthesis of a 20 mer peptide was successfully synthesized by this newly AJIPHASE® method using phase separation in very efficiently and in higher yield than previous method. One-pot peptide synthesis without all isolation steps of intermediate peptides was accomplished. This work was applied the patents for WO2012/029794 and WO2013/089241.