Efficient synthesis of a ryanodine binding inhibitor verticilide using two practical approaches

[Display omitted] •Total synthesis of symmetrical 24 membered cyclicdepsipeptide.•Solid support and hydrophobic anchor molecule are practical and efficient methods.•Preparation of α-hydroxy acid is improved by using easily available epoxy ester as chiral pool. Intracellular Ca+ release channel ryanodine receptors play a critical role in excitable tissue. They represent a highly attractive drug target to promote the possible development of selective insecticides and useful agriculture chemicals. The symmetrical 24-membered cyclic depsipeptide verticilide demonstrates selective inhibition of ryanodine-ryanodine receptor binding. Solid phase peptide synthesis and hydrophobic anchor molecule processes are practical approaches for synthesizing such compounds, and are efficient and economical methods for discovering potent candidate insecticidal compounds. Herein we describe the total synthesis of verticilde using these practical synthetic approaches.