Lactams solid-phase organic synthesis

The advent of combinatorial techniques and solid phase organic synthesis may lead to preparation of large numbers of structurally related molecules in short periods of time. This is important especially for the optimization of lead structures in the pharmaceutical industry [40]. It is now well established and documented that the combinatorial technology and solid phase techniques could offer sufficient latitude for preparation of corresponding chemical libraries with broad structural diversity. The diverse potentiality of (3-lactam moiety as specific pharmacophores and scaffolds has attracted ample interests from pharmaceutical industries for the synthetic methods based on polymer-supported techniques. 

The famous Ugi reaction, the one-pot condensation of a carboxylic acid, an amine, an aldehyde or ketone and an isocyanide to yield an a-acylaminoamide, have recently been used as an efficient method for the synthesis of diverse libraries of small organic molecules such as benzodiazepines, pyrroles, lactams and diketopiperazines2. Even though some solution-phase Ugi reactions proceed rapidly, such reactions on solid phase have been found to take between one and several days. In 1999, Hoel and Nielsen17 performed the first microwave assisted, solid phase Ugi four-component condensation (see Scheme 5.5). 

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