T22 ([Tyr5,12,Lys7]-polyphemusin II) was previously synthesized by a solid-phase method and was found to have a strong anti-human immunodeficiency virus (HIV) activity, comparable to that of 3'-azido-2',3'-dideoxy-thymidine (AZT). In the present study, the solution-phase synthesis of T22 was attempted in order to produce this peptide on a large scale. An 18-residue peptide amide corresponding to the entire amino acid sequence of T22 was synthesized by assembling four peptide fragments and two amino acid derivatives, followed by thioanisole-mediated deprotection with 1 M trimethylsilyl trifluoromethanesulfonate (TMSOTf) in trifluoroacetic acid followed by air-oxidation.