Synthetic studies for destruxins and biological evaluation for osteoclast-like multinucleated cells: a review

Synthesis of various destruxin analogs was accomplished using Shiina's macrolactonization as a key reaction. Combinatorial synthesis of cyclization precursors using solid-phase peptide synthesis and macrolactonization in solution were successful. In the synthesis of destruxin E and its analogs, the hydroxyacid-proline (HA¹-Pro²) dipeptide with an acetonide-protected diol moiety was synthesized in an asymmetric manner, and the protected diol was converted to an epoxide after macrocyclization. Destruxin E was synthesized on a gram scale using solution-phase synthesis. The structure-activity relationships of destruxins were elucidated through biological evaluation of synthetic destruxins A, B, and E and their analogs for morphological changes in osteoclast-like multinucleated cells.