Scalable Synthesis of a Key Intermediate for the Production of Pleuromutilin-Based Antibiotics

• DOI: 10.1021/acs.orglett.7b02476
• Publication Date: 2017-08-31T17:24:39Z
• Authors: Stephen K. Murphy; Mingshuo Zeng; Seth B. Herzon
• Keywords: Molecular Structure; Pleuromutilins; Polycyclic Compounds; Diterpenes; 01 natural sciences; Catalysis; Anti-Bacterial Agents; 0104 chemical sciences

An improved synthesis of an eneimide, which is a useful precursor to pleuromutilin-based antibiotics, is reported. This synthesis proceeds in six steps and 17% overall yield (27% based on recovery of a key hydrindenone intermediate) and requires two fewer chromatography steps and five fewer days of reaction time than the previously reported route. The use of expensive, acutely toxic, and precious metal reagents or catalysts has been minimized.