Total Synthesis of (+)-Spongistatin 1. An Effective Second-Generation Construction of an Advanced EF Wittig Salt, Fragment Union, and Final Elaboration

A stereocontrolled, total synthesis of (+)-spongistatin 1 (1) has been achieved. Union of a second-generation EF Wittig salt (+)-3 with the advanced ABCD aldehyde (-)-4, followed by regioselective macrolactonization and global deprotection afforded (+)-spongistatin 1 (1). The longest linear sequence, 29 steps, proceeded in 0.5% overall yield.