Identification of small molecules that selectively induce apoptosis in cancer cells

ORGN 558

Paul J. Hergenrother, Department of Chemistry, Department of Chemistry, University of Illinois, 600 S. Mathews Box 36-5, Urbana, IL 61801
The process of programmed cell death, or apoptosis, is commonly used to rid complex organisms of unwanted or damaged cells. Because of this important role in cell survival, subtle changes in the natural apoptotic cascade can have disastrous consequences. For example, an aberrant increase in apoptosis is implicated in degenerative disorders, whereas the suppression of apoptosis is a common mechanism for tumor growth. Thus, the identification of small molecules that can induce apoptosis selectively in cancerous cells versus non-cancerous cells is of great importance. Combinatorial libraries of compounds resembling known apoptosis modulators have been synthesized and their screening has identified compounds that selectively induce apoptotic death in cancer cells. A key reaction in the synthesis of these molecules was the use of the Sharpless asymmetric aminohydroxylation under pH-controlled conditions on styrene substrates to selectively provide the secondary alcohol as the major constitutional isomer.