Structure–Activity Relationship Studies on Scytophycin B, a Spiro-Epoxide-Containing Cytotoxic Macrolide

The macrolactone and side-chain fragments of scytophycin B were synthesized and their biological activities evaluated. The highlights of the synthesis for the side-chain and macrolactone fragments were the dimerization approach using cross-metathesis and the late-stage functionalization using Sharpless epoxidation. The cytotoxicity of each fragment was significantly weaker than that of scytophycin B itself, indicating that the whole structure is essential to achieve scytophycin B's potent cytotoxicity.