Sheehan JC,
Hess GP.
Massachusetts Institute of Technology, Cambridge, USA
A New Method of Forming Peptide Bonds.
J. Am. Chem. Soc. 1955;
77: 1067-1068
Key words
coupling reagents - DCC - amide bonds - penicillin V
Significance
DCC is a versatile carbodiimide reagent that is used in oxidation or dehydration reactions.
Sheehan and Hess reported the discovery of DCC for the synthesis of amides in 1955.
In subsequent work, Sheehan and his co-worker describe how DCC enabled the total synthesis
of penicillin V by formation of the central β-lactam ring (J. Am. Chem. Soc. 1957, 79, 1262). Carbodiimide reagents are still among the most widely used coupling reagents
in academia and industry.
Comment
DCC activates carboxylic acids to the O-acylisourea, which can then react with amines to from an amide bond. The reaction
proceeds fast, is high-yielding and tolerates water, and the polar side product DCU
can be removed by precipitation. However, DCC is a potent skin sensitizer and should
be handled with caution. Modern coupling reagents are water-soluble and decrease racemization
rates.
