Asparagine dehydration

DV Kashelikar, C Ressler. An oxygen-18 study of the dehydration of asparagine amide by N,N -dicyclohexylcarbodiimide and p-toluenesulfonyl chloride. J Am Chem Soc 86, 2467, 1964. 

Figure 13.10. Mechanism of dehydration of asparagine during activation [9].

Table 3 Dehydration of Unprotected Asparagine During Coupling of Boc-Asn-OH to H-X-Peptidel l...

The carboxamide groups of asparagine and glutamine derivatives 26 are susceptible to dehydration during carbodiimide-mediated esterification at the a-carboxy groups (Scheme 4).[64] reaction probably involves formation of aspartyl- or glutamylisoimide 28 by attack... 

Scheme 4 Side Reaction of Cyano Formation by Dehydration of Carboxamide Groups of Asparagine and...

Scheme 7 Dehydration of Activated Asparagine and Glutamine Residuesl ON ...

Dehydration of an amide. DCC in pyridine dehydrales curbobenzoxy-i -asparagine (1) to the corresponding nitrile (2)." ... 

The dehydration of asparagine, glutamine, and derivatives, with phosgene results in the formation of nitriles [2187] ... 

We have observed that T.B.T.U. gives a little dehydration of the side chain of asparagine. This side reaction has been confirmed by synthesis of an authentic cyanoalanyl peptide and HPLC analysis. Optimisation conditions have been found to decrease the level of this side reaction low temperature, minimisation of the quantity of diisopropylethylamine used during the coupling step and use of hydroxysuccinimide ester of asparagine as the activated aminoacid. The cyano alanyl peptide can be eliminated by preparative HPLC at the end of the synthesis. 

Addition of trapping agents such as N-Hydroxysuccinimide and 1-Hydroxybenzotriazole (HOBt) reduce the extent of many side reactions, especially Al-acylurea formation. Also, racemiza-tion is suppressed when these additives are present. The latter reagent eliminates the intramolecular dehydration of < >-amides of asparagine and glutamine that occurs with carhodiimides (eq 2). - ... 

Murphy s law certainly prevails in peptide synthesis. Some important side reactions, such as the formation of urethanes in coupling via alkylcarbonic acid mixed anhydrides or the generation of A-acylureas and dehydration of asparagine side chains when DCC is used for peptide bond formation, have already been mentioned in this chapter. Yet, countless additional side reactions and by-products have been observed and reported, often only as a footnote. Thus, it would be difficult to give a historical account of their discovery. A review [50] of side reactions noted in peptide synthesis reveals that most of them are caused by strong acids and bases, by excessive protonation or deprotonation of the amino add and peptide derivatives brought into reaction. 

Phosgene also serves as a dehydrating agent on the amide group of asparagine, glutamine and some of their derivatives [38] as shown in the following examples ... 

The 1-amino-1-deoxyketose (or ketosamine ) can dehydrate further to produce caramel-like compounds, or undergo hydrolysis to shorter chain products. If the original amine NHj-R happens to be asparagine, one of these products can be 3-APA. 

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