Microwave Enhanced N-Fmoc Deprotection

For difficult peptides, incomplete Fmoc deprotection can be a problem and use of the stronger tertiary base, l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) has been shown to increase reaction efficiency. Typically, small amounts of piperidine are 

The deprotection reaction is often performed in two stages to prevent DBF alkylation of the resin-bound terminal N -amine. The first stage is typically shorter than the second and serves to remove a significant amount of DBU from the reaction vessel before a longer deprotection reaction is employed with fresh reagent. 

Base-catalyzed aspartimide formation, which has been described in detail in the literature, can be a serious problem during chain assembly in peptide synthesis [29]. This side reaction involves attack by the nitrogen atom attached to the a-carboxy group of either aspartic acid or asparagine on the side chain ester or amide group. 

20% Piperidine in DMF 20% Piperidine with 0.1 m HOBt in DMF Hexamethyleneimine-JV-ethylpyrrolidine-HOBt in NMP-DMSO 20% Piperidine in DMF (with Hmb backbone protection) 10.90 5.55 1.49 Not detected 

Aspartimide formation has been shown to occur in sequences containing the Asp-X moiety, where X = Gly, Asn, Ser, or Thr. Each subsequent deprotection cycle after the Asp-X sequence further increases aspartimide formation. This can be a serious problem in longer peptides with multiple Asp residues. 

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