Transesterification reactions have significant roles in biological and chemical processes. In biological systems, the excision of introns and splicing of exons in pre-mRNA occur via two consecutive transesterification reactions. In synthetic chemistry, transesterification procedures have been employed to effect key transformations in the synthesis of biologically active molecules. It was discovered recently that N-heterocyclic carbenes catalyze transesterification reactions. Further investigation of transesterification processes catalyzed by carbenes will support the development of organocatalytic methods for the syntheses of biologically important molecules. ? ? Kinetic studies will be conducted to probe the mechanism of transesterification reactions catalyzed by N-heterocyclic carbenes. These studies will uncover which properties of the carbene facilitate transesterification, which will aid in the design and selection of effective catalysts to expand the scope of reactions catalyzed by carbenes. As asymmetric transformations are ubiquitous in biological systems and essential to the synthesis of therapeutic compounds, chiral carbenes will be synthesized and evaluated as catalysts for enantioselective transesterifications. A direct extension of this chemistry is the stereoselective ROP (ring-opening polymerization) of cyclic lactones, a polyesterification reaction. This polymerization method could be used to produce biodegradable polymers that are used in drug delivery systems and bioresorbable medical sutures. We will also evaluate chiral carbenes as catalysts for the asymmetric Stetter reaction to form 1,4-dicarbonyls, which are common intermediates in the synthesis of biologically active molecules. ? ?
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| Csihony, Szilard; Culkin, Darcy A; Sentman, Alan C et al. (2005) Single-component catalyst/initiators for the organocatalytic ring-opening polymerization of lactide. J Am Chem Soc 127:9079-84 |
