Driven by the FDA regulations and the growing market, there is a demanding need for technology to produce chiral pharmaceutical intermediates. Pd-catalyzed enantioselective C-C, C-N and C-O bond forming substitutions at allylic positions (allylic substitution or allylation) are an important area of current research. Many enantiomerically pure therapeutic compounds and natural products can be synthesized by employing this methodology. The design, synthesis and screening of chiral ligands, have played a pivotal role in the development of asymmetric catalysis. In Phase I, we propose to develop a new class of chiral ligands, which will be evaluated in palladium catalyze asymmetric allylic substitution (allylation) based on a standard model reaction. In Phase II, we are going to optimize the ligands and the reaction conditions. In addition, we will extend the use of the catalysts to a wide range of substrates including important drug intermediates. In Phase III, we will explore the applications in pharmaceutical and the related chemical industries and commercialize the catalysts as well as the technology for industrial and academic use.
There is an increasing need for enantiomerically pure pharmaceutical drugs. MediChem proposes to develop novel chiral carbene-transition metal catalysts for asymmetric allylic alkylation to form stereoselective carbon-carbon, carbon-nitrogen and carbon-oxygen bonds. The proposed catalysts will help synthesize pharmaceutical drugs and intermediates to be more efficient and more friendly to our environment.
| Burra, Prasad V; Zhang, Ying; Godzik, Adam et al. (2009) Global distribution of conformational states derived from redundant models in the PDB points to non-uniqueness of the protein structure. Proc Natl Acad Sci U S A 106:10505-10 |
