RGD mimics

Similarly, a 20-membered ring of a tetrapeptide derivative containing a 3-substituted cinnamic acid template was closed on a solid support [593]. This methodology was also applied in the synthesis of a small library (15 examples) of cyclic RGD mimics having a diverse array of amino acids, with a variety of ring sizes [594]. 

As described in Section 11.7.1, palladium (0) chemistry has been found particularly well-suited for constructing macrocyclic structures and, hence, applications for libraries have also been pursued. Indeed, as already noted, one of the first macrocyclic library efforts actually used the Heck reaction for solid phase construction of small collections of 20- to 24-membered semi-peptidic macrocycles (299, Figure 11.26, site of ring closure and chemistry indicated). In addition, modest-sized libraries of RGD mimic macrocycles (300) ° and macrosphelide analogues (301) were prepared using palladium-catalysed cyclocarbonylation on resin. This particular method proved to be tolerant of a variety of functional groups, including halides, ethers, ketones and esters. 

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