Identification and Total Synthesis of an Unstable Anticancer Macrolide Presaccharothriolide Z Produced by Saccharothrixsp. A1506

Saccharothriolides A–F are 10-membered microbial macrolides proposed to be generated from their precursors presaccharothriolides X–Z. Previously, we isolated presaccharothriolide X, and its unique natural prodrug-like properties have intrigued us. However, the other congeners were not detected. Herein, we detected presaccharothriolide Z using our highly sensitive labeling reagent. Moreover, chemical synthesis of presaccharothriolide Z, the first total synthesis of saccharothriolide-class macrolides, was achieved, and the structure and biological activity of presaccharothriolide Z were determined.