Carbodiimide coupling reagents

As a variation of this theme, reagents, instead of reaction substrates, can also be attached to solid supports or otherwise tagged to facilitate their separation from reaction mixtures [6]. This approach is particularly useful for reagents or reaction by-products that are difficult to remove by extraction or silica gel chromatography. Carbodiimide coupling reagents and their urea by-products are excellent examples (Fig. 9.1-l(d)). 

The first version of SPPS to be developed used the t-Boc group as the amino-protecting group. f-Boc can be cleaved with relatively mild acidic treatment and TFA is usually used. The original coupling reagents utilized for SPPS were carbodiimides. In addition to dicyclohexylcarbodiimide (DCCI), N, (V -diisopropylcarbodiimide (DIPCDI) is often used. The mechanism of peptide coupling by carbodiimides was... 

A carbodiimide-mediated reaction is usually carried out by adding the coupling reagent to a solution or mixture of the two compounds to be combined. A modified protocol involves addition of the carbodiimide to an IV-alkoxycarbonylamino add in the absence of the amino-containing component (Figure 1.15). As a result, the... 

Amino acid derivatives can be examined for enantiomeric purity by the same procedures after removal of the protecting groups. Another approach is to couple them directly with another derivative to give protected dipeptides whose diastereomeric forms are usually easy to separate by HPLC (see Section 4.11). An A-protected amino acid is coupled with an amino acid ester, and vice versa. Use of soluble carbodiimide as reagent (see Section 1.16), followed by aqueous washes, gives clean HPLC profiles. It is understood that the derivative that serves as reagent must have been demonstrated to be enantiomerically pure.43 84-89... 

Method 1 addition of a coupling reagent (carbodiimide, EEDQ, phosphonium and carbenium salts, trisubstituted phosphates, etc.) and tertiary amine, if necessary, to a mixture of the acid and the amine nucleophile that are to... 

Supported reagents have found application in many areas of synthesis including the construction of small peptides, the traditional foundation stone of solid phase synthesis. For example a recent paper describes the preparation of dipeptide p-nitroanilide and phosphonate libraries by supported carbodiimide coupling and scavenger purification (Scheme 2.52) [79]. 

Many types of mono-, bi-, and multifunctional coupling reagents are available for labeling antibodies or antigens with an enzyme. Glutaraldehyde, carbodiimide, N-succinimidyl-3-(2-pyridyldithio)propionate, and periodate oxidation of carbohydrate moieties to form active dialdehydes are several commonly used approaches in the preparation of enzyme conjugates (104-106). 

Williams, A., and Ibrahim, I. A. (1981) A mechanism involving cyclic tautomers for the reaction with nucleophiles of the water-soluble peptide coupling reagent l-ethyl-3-(3-dimethyla-minopropyl) carbodiimide (EDC). J. Am. Chem. Soc. 103, 7090—7095. 

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