Synthesis of Peptides with Mixed Anhydrides

Abstract

Abstract A mixed acid anhydride, or mixed anhydride, is a dehydration product of two polyoxy acids. For a mixed anhydride to be of interest for peptide synthesis, one of the components must, in general, be an alpha‐acylamino acid. The nature of the second component acid may vary widely. In this chapter the term mixed anhydride will be used in a more general sense. In addition to conventional mixed anhydrides, from polyoxyacids, reference will be made to “mixed anhydrides” otherwise recognizable as acyl halides, ethers, esters, thiol esters, O‐acylisoureas and isoimides. This chapter is limited to a review of chemistry of the acyclic alpha‐amino acid mixed anhydrides, which the well‐know alpha‐acylamino acid chlorides and azides, which have been the subject of an excellent review. In general, discussion of the application of alpha‐acyllamino acid mixed anhydrides will be limited to non‐polymeric peptide bond formation and will not be concerned with acylations other than those that lead to a peptide bonds.