Synthesis of Peptides with Mixed Anhydrides

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. Keywords: peptides; mixed anhydrides; amide bond formation bis(alpha-acylaminoacyl)carbonates; alpha-acylaminoacyl chlorocarbonates; alpha-acylaminoacyl alkyl carbonates. side reactions; experimental conditions