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Synfacts 2006(8): 0849-0849  
DOI: 10.1055/s-2006-941985
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart · New York

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

Contributor(s): Yasuhiro Uozumi, Yoichi M. A. Yamada
B. C. Goess, R. N. Hannoush, L. K. Chan*, T. Kirchhausen*, M. D. Shair*
Harvard University, Cambridge and Harvard medical School, Boston, USA
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Publication History

Publication Date:
21 July 2006 (online)

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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.