First Scale-Up Synthesis of FU-23, a Novel Water-Soluble Pleuromutilin-Derived Antibiotic

A first scale-up synthesis of FU-23 (1), a potent and effective water-soluble pleuromutilin-derived antibiotic, is described. The original synthesis from the medicinal chemistry group provided 1 in seven steps and 10.9% overall yield, required four chromatographies and employed expensive reagents such as AgOCN and 4-acetylsalicoyl chloride. The optimized synthetic route for the preparation of phosphate salt 1 consists of seven linear steps with a 42.8% overall yield. Significant cost reduction and more robust reaction conditions have been developed with no chromatography required at any stage.