Diketopiperazine library synthesis

Fig. 6. An early example of diketopiperazine library synthesis by Pfizer.

Hulme C, Morrissette MM, Volz FA, Bums CJ (1998) The solution phase synthesis of diketopiperazine libraries via the Ugi reaction novel application of Armstrong s convertible isonitrile. Tetrahedron Lett 39(10) 1113-1116... 

FIGURE 11.59 1,2,3,4-Tetrahydro-P-carboline-derived diketopiperazines library. (From Kundu, B., Solid-phase strategies for the design and synthesis of heterocyclic molecules of medicinal interest, Curr. Opin. Drug... 

The four component Ugi reaction is a condensation between a carboxylic acid, a ketone or an aldehyde, an amine and an isonitrile. Basically each of the reaction components can be attached to the resin. The Ugi reaction is employed for the synthesis of small molecule combinatorial libraries on solid supports. Recently a novel resin bound isonitrile has been used in the Ugi multicomponent reaction for synthesizing diversity libraries of diketopiperazines and benzodiazepindiones (Scheme 3.25) [285]. 

Other reports for the boron-Mannich reaction include the synthesis of aminophenol derivatives,561 a-arylglycines,576 a growth hormone secretagogue NN703,577 a polyhydroxyindolizine alkaloid uniflorine A,578 and cyclic ct-amino acids.579 The reaction has been applied to solution-phase reactions580 and the solid-phase reaction581-585 for the synthesis of libraries of peptides, a-amino acids, and bicyclic diketopiperazines. The reactions were accelerated by the irradiation of microwave.586... 

Falomi, M., Giacomelli, G., Nieddu, F, and Taddei, M., A new diketopiperazine tetra-carboxylic acid as template for the homogeneous phase synthesis of chemical libraries. Tetrahedron Lett., 38 (1997) 4663 666. 

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