Heterocycle library synthesis resin-bound heterocycles

A large number of drugs feature a heterocyclic component. Thus, the design, synthesis, and evaluation of heterocyclic libraries have rapidly become a major field of organic chemistry. Over the past decade, we have developed synthetic routes to a wide range of different heterocycles starting from resin-bound amino acids, short peptides, and polyamines. 

Fig. 12. Parallel synthesis of combinatorial libraries of heterocycles via resin-bound...

Using a split-and-pool combinatorial synthesis strategy, Tamanoi and coworkers developed a library of approximately 4000 heterocycles generated from resin-bound allenoates by means of phosphine catalysis [36,37]. This library was initially screened to identify GGTase I inhibitors (Table 8.1), and some potent GGTase I inhibitors with novel... 

A variety of heterocyclic compounds have been derived from the condensation of aldehydes with a-amino acids. Imines 1 (Fig. 3) are often used as intermediates in organic synthesis and are the starting point for chemical reactions such as cycloadditions, condensation reactions, and nucleophilic additions. The formation of imines via condensation of amines with aldehydes was first adopted for the reductive alkylation of resin-bound amino acids [29-31]. Imines have now been used as synthetic intermediates in the generation of a range of heterocyclic combinatorial libraries. 

The resin-bound polyamine was used as a template for the solid-phase synthesis of a range of heterocyclic compounds, such as cyclic ureas 25 and cyclic thioureas 26. This work exemplifies our ongoing efforts on the solid-phase assembly of individual acyclic and heterocyclic compounds and combinatorial libraries using short peptides as starting materials. 

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