"Chemical Equation Presented" The efficient total synthesis of the natural substance largazole is described. Using this strategy, a small library of largazole analogs was developed. Structure-activity relationship studies suggested that the geometry of the alkene in the side chain is critical. While the largazole's analogues with frans-alkene are potent for the antiproliferative effect, those with cis-alkene are completely Inactive. Most Importantly, replacement of valine with tyrosine in largazole increased selectivity toward human cancer cells over human normal cells more than 100-fold.
ASJC Scopus subject areas
- Physical and Theoretical Chemistry
- Organic Chemistry