Chapter 2 - Carboxyl Protecting Groups

Abstract

This chapter discusses carboxyl protecting groups. The purposes of carboxyl protection during peptide synthesis are to promote the solubility of reactants, to avoid reaction of the carboxylate ion with the acylating agent, and to facilitate the purification of products. The most important considerations in choosing a carboxyl protecting group are its stability during synthesis and the conditions required for its removal after it has served its purpose. Although the variety of carboxyl protecting groups currently available is adequate for the synthesis of most small peptides, there is still a definite need to develop conditions for the selective removal of a terminal carboxyl protecting group from a completely protected peptide for use in a fragment condensation scheme. The weakly basic nucleophiles, such as thiolate anions and cyanide ion, seem to offer promise in this regard, but they need to be explored further, particularly in combination with crown ethers.