Deprotection of Nin-Formyl Group on Tryptophan by Application of New Reagent, 1,2-dimethylethylendiamine in Aqueous Solution
In peptide synthesis, choosing side chain protection is one of the most important events. The Trp(Nin-For) derivative is widely used to overcome two main side-reactions occurring with Trp residue in the Boc chemistry. One problem is acid catalyzed oxidation or dimerization of the indole moiety during synthesis. The other is alkylation of the indole ring by t-butyl cation and t-butyl trifluoroacetate generated during cleavage.To date, a number of Nin-For deprotection procedures have been developed, including low-high HF treatment . However, this method involves treatment of large amount of stench reagent (dimethyl sulfide) and use of special equipment. On the other hand, the Nin-For group can be removed in a weak alkaline medium, such as 1.0 M NH2OH or 1.0 M NaHCO3. Additionally, the Nin-For group can be cleaved by dissolving Trp(Nin-For) in DMF containing a 20–30 fold molar excess of hydrazine hydrate. However, these procedures require application with excess...
KeywordsHydrazine Hydrate Dimethyl Sulfide Formyl Group Indole Moiety Alkaline Reagent
The authors gratefully acknowledge Dr. Kiyoshi Ogawa at the Asahi Kasei Pharma Corp. for helpful analysis of RP-HPLC, LC/MS and LC/MS/MS.