Peptides tripeptide catalysis

An interesting example of intramolecular catalysis of type A syntheses is provided by the ready condensation of certain histidylproline peptides. Treatment of the ditrityl derivative of the tripeptide 121 with 50% acetic acid at room temperature results in rapid detritylation followed by cyclization to give the diketopiperazine 122 with elimination of... 

Exchange studies with di- and tripeptides (Nielsen et ai, 1960) gave results similar to those obtained in the case of JV-methylacetamide. The rates varied with pD, indicative of acid and base catalysis, and the minimum rates ( 0.6min for glycylglycine and 0.3 min for the JV-terminal peptide group of alanylglycyl-... 

Mechanistic studies performed by Wennemers and coworkers revealed that the presence of water significantly reduces the reaction rate of peptide-catalysed Michael additions. In order to make the reaction water compatible, the group of Wennemers studied the asymmetric Michael addition in aqueous emulsions supported by tripeptides equipped with alltyl moieties that are supposed to provide a hydrophobic environment for catalysis, similar to the behaviour of enzymes. While the parent peptide 15b showed, under these conditions, low conversion rates and a decreased enantiomeric excess of 73%, the insertion of hydrophobic allqrl side ehains improves the catalyst s performance (21, Scheme 13.14c) by shielding the catalytically active peptide from the surrounding water allowing the addition to proceed in a hydrophobic microenviroment, as previously assumed. The prepared addition products were isolated in good yield and with excellent diastereo- and enantioselectivity." " ... 

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