Solid Phase Peptide Synthesis employing Haloacylpolystyrene as a Polymer Support

A modified solid phase method for peptide synthesis employing haloacyl polystyrene resins is described. For this purpose, several kinds of haloacylated copolystyrene-divinylbenzene were prepared, of which the bromoacetyl derivative was of choice. Protected amino acids could be attached to or released from this type of resin more smoothly than in the case of the benzyl type. Protected amino acids and their amide, hydrazide and ester derivatives were obtained by cleavage of the amino acid resins (III) by means of alkaline aqueous dioxane, sodium thiophenoxide in dimethylformamide, methanolic ammonia, hydrazine hydrate in methanol or methanol containing a catalyst under mild reaction conditions. This modification was successfully applied to syntheses of several small peptides. Although the overall yields were slightly lower than in the original solid phase method, the peptides and their C-terminal amide derivatives could be prepared easily with preservation of all the protecting groups on them. Therefore, this method may also be useful for the preparation of peptide fragments in larger polypeptide synthesis.