Usefulness of the phthalimidomethyl group for the reversible protection of carboxyl functions

Abstract

AbstractThe stability of the ester bond in phthalimidomethyl benzoate has been tested under a wide variety of circumstances, applied for the removal of protecting groups from amino acids. The chemical properties of the ester (table I) warranted the expectation that the phthalimidomethyl group would be useful for the protection of carboxyl functions in peptide syntheses.Several amino acid esters of phthalimidomethanol (table III) have been prepared by simple methods. Some of these compounds have been converted into peptides by conventional routes (table IV). No racemization was observed during these reactions.The usefulness of the phthalimidomethyl esters in peptide syntheses has been investigated further with amino acid and peptide esters containing also amino or other carboxyl protecting groups (benzyloxycarbonyl, benzyl, p‐nitrobenzyl or tert.‐butyl). In all cases the phthalimidomethyl group as well as the other substituents could be removed separately and very specifically, giving pure products in satisfactory or good yields (see e.g. schemes A and B).