05 April 2012 (eFirst)
N,N′-Diisopropylcarbodiimide (DIC) is a liquid carbodiimide used in peptide synthesis and contains the functional group RN=C=NR. Carbodiimides hydrolyze to form ureas, which makes them uncommon in nature. Between the different sources of carbodiimide coupling reagents in peptide synthesis, the use of DIC as a liquid carbodiimide is more convenient. By using DIC one can avoid the tedious removal of dicyclohexylurea (DCU) formed during the use of dicyclohexylcarbodiimide (DCC),[ 1 ] as diisopropylurea (DIU) is comparatively easy to remove at the time of purification, which is formed after the generation of peptide bond. Besides being a less expensive and commercially available reagent, DIC is a good coupling agent and widely used in solid-phase peptide synthesis. As a liquid, it is easier to handle than the commonly used DCC.
Carbodiimides are formed by dehydration of ureas or from thioureas. They are also formed by treating organic isocyanates with suitable catalysts (generally based on phosphine oxides); in this process, carbon dioxide evolves from the isocyanate.[ 2 ]
In synthetic organic chemistry, compounds containing the carbodiimide functionality are dehydrating agents and are often used to activate carboxylic acids towards amide or ester formation.[ 3 ] Additives, such as N-hydroxybenzotriazole or N-hydroxysuccinimide, are often added to increase yields and decrease side reactions. Carbodiimides can also react with amines to form guanidines.
- 1 Izdebski J, Orlowska A, Anulewicz R, Witkowska E, Fiertek D. Int. J. Pept. Protein Res. 1994; 43: 184
- 2 Monagle JJ. J. Org. Chem. 1962; 27: 3851
- 3 Angell YM, García-Echeverría C, Rich DH. Tetrahedron Lett. 1994; 35: 5981
- 4 Cornier PG, Boggián DB, Mata EG, Delpiccolo CM. L. Tetrahedron Lett. 2012; 53: 632
- 5 Fara MA, Díaz-Mochón JJ, Bradley M. Tetrahedron Lett. 2006; 47: 1011
- 6 Bacsa B, Horváti K, Bõsze S, Andreae F, Kappe CO. J. Org. Chem. 2008; 73: 7532
- 7 Zhu X, Zhu Du. Xu F., Shen Q. 2009; 74: 6347
- 8 Cho S, Choi J, Kim A, Lee Y, Kwon Y.-U. J. Comb. Chem. 2010; 12: 321
- 9 Liu Z, Nefzi A. J. Comb. Chem. 2010; 12: 566
- 10 Verma A, Verma SS, Saraf SK. J. Heterocycl. Chem. 2010; 47: 1084
- 11 Liu B, Yang Y, Cui D, Tang T, Chena X, Jinga X. Dalton Trans. 2007; 4252