Premium
Application of N im ‐2,6‐Dimethoxybenzoyl Histidine in Solid‐Phase Peptide Synthesis
Author(s) -
Zaramella Simone,
Strömberg Roger,
Yeheskiely Esther
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200200668
Subject(s) - chemistry , racemization , dipeptide , imidazole , histidine , peptide synthesis , residue (chemistry) , peptide , fast atom bombardment , high performance liquid chromatography , protecting group , solid phase synthesis , hydrolysis , intramolecular force , nitrogen atom , amino acid , mass spectrometry , stereochemistry , organic chemistry , chromatography , group (periodic table) , alkyl , biochemistry
Fmoc‐histidine derivatives protected with 2,6‐dimethoxybenzoyl (2,6‐Dmbz) units, either on the τ‐ ( 1 ) or on the π‐position ( 2 ) of the imidazole residue, have been prepared and applied to the synthesis of the dipeptide Fmoc‐His(2,6‐Dmbz)‐Val‐OMe, with high coupling efficiencies (99 and 95%, respectively) and low racemization (0.3 and 0.1%, respectively), as ascertained by HPLC analysis on the fully protected dipeptides. In addition, the hexapeptide H‐Ala‐Ser‐Val‐His‐Val‐Phe‐OH ( I ) has been synthesized on a solid support employing the novel building blocks 1 and 2 as well as commercially available Fmoc‐His(τ‐Trt)‐OH ( 3 ). The crude deprotected products were analyzed by reverse‐phase HPLC and mass spectrometry, which indicated that when the τ‐protected derivatives 1 and 3 were employed the products were of comparable quality (93−94% major peak). The hexapeptide synthesized with the π‐protected histidine 2 was contaminated with a product corresponding to 2,6‐Dmbz‐His‐Val‐Phe‐OH ( 12 ), which was probably formed through the intramolecular acyl transfer of a 2,6‐Dmbz unit from the π‐nitrogen atom to the α‐amino group of the N‐terminal histidine unit upon removal of the Fmoc group. This side reaction was insignificant (less than 0.5%) when using the τ‐protected derivative 1 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)