Dynamic combinatorial chemistry using amino acids as building blocks, and use of carbonyl ylides as dipoles in dipolar cycloadditions

Over the past decade, combinatorial chemistry has been widely used to create large libraries of compounds and to screen them to find new materials and biologically active molecules. A more specific approach is dynamic combinatorial chemistry. Constituents of the library are formed through reversible bonds between small components, and each of the constituents is in thermodynamic equilibrium in the reaction mixture. When a specific target is added to the library, the constituent that has the best binding feature with the target is selectively expressed, and the equilibrium is shifted to this specific compound. We were interested in studying the comportment of simple amino acid derivatives toward dynamic combinatorial chemistry. An alkyl chain containing a terminal double bond was added to amino acids to form the building blocks. We first synthesized homodimers from each building block through cross-metathesis using Grubbs' second generation catalyst to study them. Then the amino acid derivatives were mixed with the catalyst to form a library of dimers. The addition of a cation in the mixture under specific conditions shifted the equilibrium. All the results were analyzed by HPLC.;The second project was focused on the formation of heterocycles using 1,3-dipolar cycloadditions. Dipolar cycloadditions have been an efficient method to quickly form heterocycles, and have been especially used for the synthesis of natural products. Among the different dipoles available for the 1,3-dipolar cycloadditions, we studied the use of a cyclic carbonyl ylide as dipole. The use of this particular dipole with appropriate dipolarophiles can lead to highly substituted oxygen heterocycles. The compounds obtained from the reaction with the carbonyl ylide and various dipolarophile were analyzed. After having formed the precursor of the carbonyl ylide from levulinic acid, it was mixed with a rhodium catalyst and a dipolarophile. Various dipolarophiles, containing either electron-withdrawing groups or electron-donating groups, were tested. The stereochemistry of the compound obtained was analyzed and explained in terms of frontier molecular orbital theory.