The first preparative solution phase synthesis of melanotan II

• Vladimir V. Ryakhovsky,
• Georgy A. Khachiyan,
• Nina F. Kosovova,
• Elena F. Isamiddinova and
• Andrey S. Ivanov

Beilstein J. Org. Chem. 2008, 4, No. 39, doi:10.3762/bjoc.4.39

• Vladimir V. Ryakhovsky Georgy A. Khachiyan Nina F. Kosovova Elena F. Isamiddinova Andrey S. Ivanov R&D Dept., Pharm-Sintez, 38 Shosse Entusiastov, 111123 Moscow, Russia 10.3762/bjoc.4.39 Abstract Melanotan II is a synthetic cyclic heptapeptide used to prevent a sunlight-induced skin cancer by

• γ-carboxy group of aspartic acid, led to a cyclic intermediate. Appending N-acetylnorleucine concluded the assembly of melanotan II molecule. Protection of the lateral groups in arginine and tryptophan was omitted for atom and step economy reasons. The total synthesis of melanotan II was

• accomplished in 12 steps with 2.6% overall yield, affording >90% pure peptide without using preparative chromatography. Keywords: melanotan II; solution phase synthesis; peptide synthesis; Introduction Development of solid phase peptide synthesis methodology [1], recombinant techniques for expressing