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The aspartimide problem in Fmoc‐based SPPS. Part III
Author(s) -
Mergler M.,
Dick F.
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.668
Subject(s) - chemistry , piperidine , peptide , derivative (finance) , protecting group , combinatorial chemistry , beta (programming language) , stereochemistry , organic chemistry , biochemistry , computer science , programming language , alkyl , financial economics , economics
A newly developed Fmoc‐Asp derivative, Fmoc‐Asp β‐(2,3,4‐trimethyl‐pent‐3‐yl) ester, has been tried in the Fmoc‐based SPPS of H‐Val‐Lys‐Asp‐Xaa‐Tyr‐Ile‐OH, a well‐established peptide model for studying base‐catalysed aspartimide formation. When synthesizing the hexapeptide incorporating Gly, Arg(Pbf), Asn(Mtt), Asp(OtBu) or Cys(Acm) for Xaa, considerable amounts of aspartimide‐related by‐products were to be expected. The Asp 3 β‐carboxy protecting group and the duration of exposure to bases were varied. By‐product formation could be reduced by incorporation of the new Asp derivative more efficiently than by introducing the less bulky Asp(OMpe). Significant improvements were observed in cases of prolonged contact with piperidine or DBU. Both β‐carboxy protecting groups were superior to the standard Asp(OtBu) which was also included in this study, but the additional stabilization gained by our new protecting group was valuable especially in syntheses of long peptides or difficult sequences. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.