Parallel Synthesis and Biological Evaluation of Destruxin E Analogs Modified with a Side Chain in the α‐Hydroxycarboxylic Acid Moiety

Abstract

Synthesis and biological evaluation of destruxin E analogs possessing various functional groups in the α‐hydroxycarboxylic acid moiety have been achieved. The (S)‐epoxide moiety in the side chain of α‐hydroxycarboxylic acid could be an essential factor for the induction of morphological changes in OCLs at a lower concentration.

Abstract

This study demonstrates the synthesis and biological evaluation of destruxin E analogs possessing various functional groups in the α‐hydroxycarboxylic acid moiety. Parallel synthesis of eleven analogs was successfully achieved through solution‐phase peptide synthesis and macrolactonization. Biological evaluation of the synthetic analogs using osteoclast‐like multi nuclear cells (OCLs) revealed that the epoxide group in the side chain of α‐hydroxycarboxylic acid and the orientation of the oxygen atom are essential factors in the desired potent activity that induces morphological changes in OCLs for the inhibition of bone‐resorbing activity.