Diversity-Oriented Synthesis of a 10,102-Membered Library of Carpanones

Significance

Split-and-pool synthesis of a 10,102-membered encoded library of carpanone analogues was developed for the construction of diversity-oriented-synthesis (DOS) libraries around core structures of carpanone. Thus, the high-capacity (500 µm) polystyrene-resin-supported intermediate 1 with a carpanone-like core was converted into 716 kinds of oximes A including amides, ureas, triazoles, sulfonamides or thioethers, 578 kinds of phenols B, and 8,670 compounds of type C. Using whole-cell fluorescence imaging, a series of molecules that inhibit exocytosis from the Golgi apparatus was discovered in the DOS library (most potent: CLL-19; IC₅₀ = 14 µM). Structure-activity relationships for the molecular exhibiting of this phenotype was also reported.