This grant in the Organic and Macromolecular Chemistry Program suppports research by Dr. Marco Ciufolini. The methodology being developed by Dr. Ciufolini has the potential for becoming a new standard route for the synthesis of nitrogen containing materials. This class of materials is extremely important in substances found in both medicine and agriculture. The rearrangement of N-acyl-2-furylamines to N-acyl-2-alkyl-piperidin-3-ones (termed the "Aza-Achmatowicz" reaction) will be developed into a general method for the total synthesis of optically active nitrogenous substances. A key step of the new technique involves enzymatic resolution of racemic furylglycines. The resolved aminoacids, which will be stereochemically correlated with (L)-Serine, are readily and efficiently transformed into valuable building blocks for the synthesis of structures as diverse as, e.g., azasaccharides, beta-lactams, unusual aminoacids, and amphibian alkaloids. A number of issues in organic methodology will be confronted in connection with the total synthesis of members of those general classes of compounds. The stereochemical course of enolate alkylations, conjugate additions of organocopper reagents and oxidation reactions will be investigated in detail using the rearranged materials as substrates. The directing effect of N-centered functionalities on the stereochemical course of reactions at neighboring olefinic subunits will be studied. New methodology will be developed based on the chemistry of enamides. Ultimately, the Aza-Achmatowicz reaction will be refined enough to be used for the construction of N-containing carbon frameworks considerably more complex than the ones planned in this research.
