Application of hexafluoroacetone as protecting and activating reagent in solid phase peptide and depsipeptide synthesis

Hexafluoroacetone-protected/activated hydroxy acids [2,2- bis(trifluoromethyl)-1,3-dioxolan-4-ones] represent recoverable and reusable monomers for the solid phase synthesis of depsipeptides. The reactivities of HFA-protected/activated malic acid and its C^α-methylated analog citramalic acid toward resin bound amino acids were studied and are compared herein. The potential of HFA-protected/activated amino acids [2,2-bis(trifluoromethyl)-1,3-oxazolidin-5-ones] such as Phe, Leu, MeLeu, Pro and Tic as pre-activated monomers for solid phase peptide synthesis was also investigated.