Synthesis of a 10,000-membered library of molecules resembling carpanone and discovery of vesicular traffic inhibitors

J Am Chem Soc. 2006 Apr 26;128(16):5391-403. doi: 10.1021/ja056338g.


Split-and-pool synthesis of a 10,000-membered library of molecules resembling the natural product carpanone has been achieved. The synthesis features development of solid-phase multicomponent reactions between nitrogen nucleophiles, enones, and hydroxylamines, and a solid-phase application of the Huisgen cycloaddition affording substituted triazoles. The synthesis was performed in high-capacity (500 microm) polystyrene beads using a one bead-one stock solution strategy that enabled phenotypic screens of the resulting library. Using whole-cell fluorescence imaging, we discovered a series of molecules from the carpanone-based library that inhibit exocytosis from the Golgi apparatus. The most potent member of this series has an IC(50) of 14 microM. We also report structure-activity relationships for the molecules exhibiting this interesting phenotype. These inhibitors of exocytosis may be useful reagents for the study of vesicular traffic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biological Products / chemistry*
  • Biological Products / pharmacology
  • Exocytosis / drug effects
  • Fluorescence
  • Golgi Apparatus / drug effects
  • Structure-Activity Relationship


  • Biological Products