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Synfacts 2020; 16(04): 0475
DOI: 10.1055/s-0040-1707567
Chemistry in Medicine and Biology
© Georg Thieme Verlag Stuttgart · New York

A Classic Way of Forming Amide Bonds

Contributor(s):
Dirk Trauner
,
Belinda E. Hetzler
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
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Further Information

Publication History

Publication Date:
18 March 2020 (online)

 
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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.


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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.


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