Synthesis of β‐Secretase Inhibitors Containing a Hydroxyethylene Dipeptide Isostere

Abstract

β‐Secretase inhibitors with a Leu*Ala hydroxyethylene dipeptide (HED) isostere have been an especially interesting topic in recent years. In this study, a template compound 17 was synthesized, featuring truncation at the P₂′ position and changes at P₂ and P₃, which differs from other reported potent inhibitors. The purpose was to explore optimal reaction conditions and construct an inhibitor library to investigate ideal protein–substrate interaction.

Keywords:

• hydroxyethylene dipeptide isostere
• peptidomimetics
• β‐secretase
• synthesis

Acknowledgment

This work was supported by the National Natural Science Foundation of China (Nos. 20272004 and 20572006) and the 985 program, Ministry of Education of China.