Combinatorial chemistry strategies using a multi-component condensation

Multiple component condensations contribute significantly to the strategy of combinatorial chemistry. This dissertation focuses on parallel synthesis strategies using the Ugi reaction. The Ugi reaction combines an amine, carbonyl compound. isocyanide. and carboxylic acid to form an N-acyl-N-alkyl-α-amino amide in one step.; The Ugi four-component condensation is used in the parallel synthesis of sialyl Lewis x glycomimetics. The synthesis of C-glycosides and methodology for the deprotection of C-glycosides on solid support is demonstrated. An Ugi reaction using a di-acid and solid supported amine is described.; The issue of limited isocyanide diversity is addressed. A number of methods to modify available isocyanides and the synthesis of isocyanides from different functional groups are described. In particular, a useful transformation from epoxides to isocyanides is demonstrated. These isocyanides are used in the Ugi reaction as a direct way to introduce isocyanide diversity.; Our group introduced the convertible isocyanide to address the issue of limited isocyanide availability. The convertible isocyanide is such that the isocyanide formed amide of the resultant Ugi product can be converted to an alternative functional group. Work in this dissertation improves on the synthesis of the convertible cyclohexenyl isocyanide as well as the synthesis of alternative vinyl isocyanides. A convertible isocyanide on solid support is demonstrated.; A combinatorial approach towards carfentanil related analgesics demonstrates the power of a multi-component reaction followed by resin capture. Primary amines and 1,5-dichloro-3-pentanone combine to generate diverse 4-piperidinones. These cyclic ketones condense in the Ugi reaction with the convertible cyclohexenyl isocyanide, carboxylic acids, and primary amines or anilines. Resin capture of the crude Ugi products, followed by TTA cleavage, provides pure compounds. Methanolysis of the Ugi products provides direct carfentanil analogs.; This library of carfentanil analogs demonstrates our ideal parallel synthesis strategy combining the best of solution and solid phase chemistry with resin capture and the Ugi four-component condensation.