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Formation of Fmoc–β‐alanine during Fmoc‐protections with Fmoc–OSu
Author(s) -
Obkircher Markus,
Stähelin Christian,
Dick Fritz
Publication year - 2008
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.1001
Subject(s) - chemistry , reagent , yield (engineering) , deprotonation , combinatorial chemistry , peptide , peptide synthesis , alanine , amino acid , organic chemistry , biochemistry , ion , materials science , metallurgy
During the Fmoc‐protection of H–α‐Me–Val–OH, an unknown side product was found and isolated. The characterization using various analytical methods led unambiguously to the result that Fmoc–β‐Ala–OH was formed during the reaction. The reagent Fmoc–OSu was proven to be the source of Fmoc–β‐Ala–OH, following a mechanism that involved many deprotonation and elimination steps and a Lossen‐type rearrangement as key sequence. The impurity Fmoc–β‐Ala‐OH was found in a variety of reactions in which Fmoc–OSu was applied, either in the reaction mixture or as a contamination of the crude product. Purification of the Fmoc–amino acid derivatives from this impurity incurred high costs and significant reductions in yield. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.