Motilin and [D-Phe¹]-motilin were synthesized via the corresponding sulfoxide (Met¹³). The protected Met (O)¹³-motilin and [D-Phe¹, Met (O)¹³]-motilin, in which Met residue was substituted by Met (O) residue, were constructed from three suitable subunits, respectively. The protected peptides were deblocked by methanesulfonic acid in the presence of anisole to obtain Met (O)¹³-motilin and its D-Phe¹-derivative, and the resulting Met (O)-peptides were finally reduced by thiol to give the desired docosapeptides, motilin and D-Phe¹-motilin.