Formation of Fmoc-beta-alanine during Fmoc-protections with Fmoc-OSu.
During the Fmoc-protection of H-alpha-Me-Val-OH, an unknown side product was found and isolated. The characterization using various analytical methods led unambiguously to the result that Fmoc-beta-Ala-OH was formed during the reaction. The reagent Fmoc-OSu was proven to be the source of Fmoc-beta-Ala-OH, following a mechanism that involved many deprotonation and elimination steps and a Lossen-type rearrangement as key sequence. The impurity Fmoc-beta-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.
Obkircher
Markus
M
Bachem AG, Bubendorf, Switzerland.
Stähelin
Christian
C
Dick
Fritz
F
D000409:Alanine / Q000138:chemical synthesis* / Q000737:chemistry; D005452:Fluoresceins / Q000138:chemical synthesis* / Q000737:chemistry; D013058:Mass Spectrometry
D005452:Fluoresceins; D000409:Alanine