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

• and Discussion To date, several accounts of solid phase synthesis of peptide 2 have been reported. A representative one, reported by Hruby and co-workers, exploited p-methylbenzhydrylamine resin (pMBHA) as the solid support and tert-butyloxycarbonyl (Boc) tactics for temporary protection of α-amino

A practical synthesis of the ¹³C/¹⁵N- labelled tripeptide N-formyl- Met-Leu-Phe, useful as a reference in solid- state NMR spectroscopy

• Sven T. Breitung,
• Jakob J. Lopez,
• Gerd Dürner,
• Clemens Glaubitz,
• Michael W. Göbel and
• Marcel Suhartono

Beilstein J. Org. Chem. 2008, 4, No. 35, doi:10.3762/bjoc.4.35

• , reflux, 24–65 h) were required to couple the first Boc-protected amino acid to the solid support (chloromethyl resin) and long reaction times (18 h) were necessary to attach further building blocks to the growing peptide chain. The formylation of the N-terminus with formic acid/acetic anhydride was

• . Results and Discussion Peptide Synthesis The synthesis of the MLF tripeptide started with the immobilisation of 13C/15N-labelled Fmoc-Phe-OH to the solid support (Wang resin 2). This esterification step, leading to 3 quantitatively, was performed by activating the COOH group with MSNT under mild reaction

• conditions (Scheme 1) [13]. Full conversion of the resin bound hydroxy groups could be demonstrated by a colourimetric test with Dabcyl-COOH [14]. After removal of Fmoc with piperidine, the 13C/15N-labelled monomers Fmoc-Leu-OH and Fmoc-Met-OH were successively coupled to the solid support with DIC/HOBt [15