Exciting challenges for chemical synthesis

BIOL 148

Samuel J. Danishefsky, danishes@mskcc.org, Bioorganic Chemistry, Kettering Chair, Memorial Sloan-Kettering Cancer Center; Department of Chemistry, Columbia University, 1275 York Ave, Box 106, New York, NY 10021
The talk will attempt to demonstrate by example that there have been major advances in the methodology of chemical synthesis. The remarkable discoveries in the field of synthetic methodology, in particular, through the use of organometallic catalysis, have enabled chemical synthesis to attack much more ambitious agenda problems than was hitherto possible. In our judgment, it is primarily advances in chemical methodology, which have enabled new insights at the strategic level.

The lecture will show by illustration that these advances can serve to enhance the possibilities of utilizing small molecule natural products and not-so-small biologically active substances, as entry points for medicinal discovery. The tendency to down-grade the utility of natural product leads in pharma discovery arose from concerns primarily about issues of compound availability. The revolution in the power and reach of synthesis described above has altered the paradigm.