Melanotan II is a synthetic analogue of α-melanocyte-stimulating hormone (α-MSH), which is a peptide hormone.

A solid-phase synthesis method for Melanotan II is characterized by the following steps: first, using an Fmoc-linker-aminomethyl resin as the support; then, sequentially coupling amino acids according to the Fmoc/tBu solid-phase peptide synthesis method and performing acetylation; subsequently, removing the trifluoroacetyl and methyl ester groups from the amino acids via hydrolysis using a 1–2 N NaOH solution and dioxane (with a volume ratio of NaOH to dioxane ranging from 1:1 to 1:4); then, performing cyclization directly on the resin using a condensing agent; and finally, cleaving the peptide from the resin using a mixture of trifluoroacetic acid, water, thioanisole, and 1,2-ethanedithiol in a ratio of 92.5:2.5:2.5:2.5. The resulting crude Melanotan II is purified and converted to the acetate salt via preparative HPLC, followed by freeze-drying to yield Melanotan II acetate. The amino acids employed include Fmoc-Lys(Tfa)-OH, Fmoc-Trp(Boc)-OH, Fmoc-Arg(Pbf)-OH, Fmoc-D-Phe-OH, Fmoc-His(Trt)-OH, Fmoc-Asp(OMe)-OH, and Fmoc-Nle-OH.