One-pot protection and activation of amino acids using pentafluorophenyl carbonates

Protection of the amino group and activation of the carboxylic acid groups are the most important steps associated with any peptide synthesis protocol; hence, a one-pot process to achieve these is highly desirable. A possible strategy is to use pentafluorophenyl carbonates to simultaneously protect the amino group as a carbamate derivative and activate the carboxylic acid group as a pentafluorophenyl ester. A detailed study is carried out to understand the scope and limitations of this method using five different pentaflurophenyl carbonates. The efficiency of these one-pot reactions depends largely on the nature of the pentafluorophenyl carbonates and also on the nature of the amino acids. Electron deficient and sterically less demanding carbonates reacted faster than the others, whereas amino acids with longer aliphatic side chains gave better yields than more polar amino acids. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.