Pot-economical synthesis of cyclic depsipeptides using a hydrophobic anchor molecule toward the construction of an unnatural peptide library

Abstract

Cyclic peptides and cyclic depsipeptides are important sources of novel lead compounds in drug discovery research. However, solid phase peptide synthesis strategies used for their synthesis has points to be improved such as reaction monitoring, confirmation of the product, scale-up, and the use of excess reagents. We are addressing these issues and here report a one-pot economical unit elongation method using a hydrophobic anchor molecule. We achieved the total synthesis of the 24-membered cyclic depsipeptide emodepside and PF1022s, which exhibit anthelmintic activity, using a hydrophobic anchor molecule method. Furthermore, we established a process for synthesizing bioactive compounds in one reaction vessel and achieved the one-pot total synthesis of emodepside. Since the final product can be obtained without taking out the intermediates of each step from the reaction vessel, this synthesis approach is likely applicable to parallel synthesis methods.