Synthesis and purification of aggregation-prone hydrophobicpeptides by the incorporation of an Fmoc dipeptide withthe peptide bond protected with a modified 2-hydroxy-4-methoxybenzyl (Hmb) group

• Published in: Tetrahedron letters 2008, Vol.49 (24), p.3921
• Main Authors: Wahlström, Karolina, Planstedt, Ove, Undén, Anders
• Format: Article
• Language: English
• ISSN: 1359-8562; 0040-4039
• DOI: 10.1016/j.tetlet.2008.04.055

The dipeptide Fmoc-Val-(2-hydroxy-4-methoxybenzyl)Gly-OBzl was synthesized and the 2-hydroxyl group carbamoylated to give a Boc-N(CH(3))CH(2)CH(2)N(CH(3))CO-, (Boc-Nmec-) modification of the 2-hydroxy-4-methoxybenzyl (Hmb) group. After catalytic hydrogenation and purification, the resulting dipeptide Fmoc-Val-(Boc-Nmec-Hmb)Gly-OH was used in solid phase peptide synthesis. During treatment with TFA, the peptide was released from the resin and the Boc group cleaved. The peptide could then be purified with an alkylated peptide bond carrying a cationic charge that both increased the solubility of the peptide during the purification steps and facilitated analysis by MALDI-TOF mass spectrometry. The Nmec group was cleaved by intramolecular cyclization under slightly alkaline conditions, followed by cleavage of the Hmb group by TFA to give the fully deprotected peptide.