Solution-phase combinatorial synthesis; Peptide derivatives of ethyl p-aminobenzoate

The need to find more efficient and cost-effective methods of drug development has led pharmaceutical companies to examine combinatorial means of synthesis. The ability to carry out parallel synthesis by the hundreds of compounds is rapidly advancing synthetic, analytical, and biological research. In this thesis project, peptide derivatives of ethyl paminobenzoate were synthesized via solution phase combinatorial techniques. A total of 27 tri-peptide analogs were produced, using a polymer-supported carbodiimide resin as the coupling agent. The structures of all products and intermediates were confirmed by LC-MS. Two methods were used for sequential deprotection of these analogs. The traditional method using the mild base, piperidine, was used as well as a polymersupported thiophenol method. Upon comparison of both methods, we concluded that the piperidine deprotection afforded a higher yield of the desired unprotected peptide