Sch 53825

Two novel phospholipase D (PLD) inhibitors, Sch 53823 (I) and Sch 53825 (II), were isolated from a fungal culture.The acetylated derivatives, Sch 53827 and Sch 53829, were prepared for the purpose of structure determinationThe extensive NMR studies of Sch 53827 and Sch 53829 including DEPT, COSY, NOESY, HETCOR, and selective INEPT experiments permitted the establishment of their structures, as well as relative stereochemistries.Among these compounds, Sch 53827 exhibited the most potent inhibitory activity in the phospholipase D assay with the IC₅₀ = 17 μM.

The first total synthesis of Sch 53825 (14) was achieved in 12 steps from 5-hydroxy-1-tetralone in 16% overall yield throughN-benzyl cinchoninium chloride-catalyzed asymmetric epoxidation and a Mitsunobu reaction as the key steps.