Schlack-Kumpf reaction

What is Schlack-Kumpf reaction?

The Johnson reaction, first described in 1911 by Johnson, involves the synthesis of 2-thiohydantoins from α-amino acids using thiocyanate and acetic anhydride. Schlack and Kumpf subsequently employed this reaction in 1926 to sequence peptides and proteins from the C-terminal, which is why it is also referred to as the Schlack-Kumpf reaction.

Schlack-Kumpf reaction - general reaction scheme
Schlack-Kumpf reaction

Schlack-Kumpf reaction proceeds by activating the terminal carboxyl group through the formation of a mixed anhydride with acetic anhydride, which reacts with ammonium thiocyanate to yield a peptidyl 2-thiohydantoin. The 2-thiohydantoin is then separated from the peptide chain to expose the second carboxyl group as the new terminal carboxyl group through treatment with a base.

However, Schlack-Kumpf reaction suffers from a few limitations, including the severity of the conditions required for the complete conversion of the terminal carboxyl group into peptidyl 2-thiohydantoin and its cleavage. Moreover, the corresponding 2-thiohydantoin derivatives are difficult to form for certain amino acids, such as C-terminal aspartate, proline, lysine, glutamine, glutamate, and arginine.

References

  • Johnson, T. B. and Nicolet, B. H., J. Am. Chem. Soc., 1911, 33, 1973
  • Johnson, T. B. and Scott, W. M., J. Am. Chem. Soc., 1913, 35, 1136
  • Schlach, P. and Kumpf, W., Z. Physiol. Chem., 1926, 154, 125
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