TRIPHENYLPHOSPHINE SULFUR TRIOXIDE ADDUCT AS A COUPLING REAGENT IN PEPTIDE-SYNTHESIS

Several adducts of sulfur trioxide with electron-donor molecules have been prepared. Of these the air-stable triphenylphosphine-SO3 complex has been shown to be the most useful in the synthesis of peptides. It has been demonstrated that a variety of solvents may be used for couplings, but that in order for reaction to occur the solvent must itself be able to form an adduct. This behaviour is due to the fact that SO3 is transferred from the triphenylphosphine-SO3 complex to the solvent, thus forming an intermediate complex which is responsible for activation of the carboxylate unit. The carboxyl component is generally present as its tetramethylguanidinium salt. The method has been used to synthesize several model peptides and to prepare a fully biologically active sample of methionine-enkephalin. © 1979.