Proline-based macrocycles

Chen KX, Njoroge FG, Arasappan A, Venkatraman S, Vibulbhan B, Yang W, Parekh TN, Pichardo J, Prongay A, Cheng KC, Butkiewicz N, Yao N, Madison V, Girijavallabhan V (2006) Novel potent hepatitis C vims NS3 serine protease inhibitors derived from proline-based macrocycles, J Med Chem 49 995-1005... 

Based on the research by Kubik and Goddard on L-proline-derived cyclic peptides that bind ammonium salts [102], Sanders et al. prepared a small DCL derived from building block 15. Exposure of the DCL to the cationic guest acetylcholine resulted in the ampHfication of the expected trimeric receptor 17 (Figure 3.7) [66]. Although the trimer macrocycle was expected to be the best receptor as it resembles the compound in Rubik s original report, binding affinities of trimer and dimer 16 for the template were not compared because of solubility problems. 

In 1971, Davankov et al. achieved the first baseline separation of enantiomers using a small molecule-based CSP consisting of L-proline [1], Since then, a wide range of chiral small compounds, which include amino acids, cyclodextrins, macrocyclic glycopeptides, cinchona alkaloids, crown ethers, jt-basic or rt-acidic aromatic compounds, etc., have been used as CSPs [2—6], On the other hand, the polymer-based CSPs are further divided into two categories, i.e., synthetic and natural chiral polymers [7, 8]. Typical examples of the synthetic polymers are molecularly imprinted polymer gels, poly(meth)acrylamides, polymethacrylates, polymaleimides, and polyamides, and those of the natural polymers include polysaccharide derivatives and proteins. 

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