Amide-bond formation

Couple the two protected ammo acids by amide bond formation between them... 

FIGURE 27 13 The mechanism of amide bond formation by W W dicyclohexylcarbodiimide promoted condensation of a carboxylic acid and an amine... 

This group was developed for the protection of primary amides of amino acids. It is introduced by amide bond formation with the benzhydrylamine. It is cleaved with 1 MSiCl4/anisole/TFA/0° or 1 MTMSOTf/thioanisole/TFA, 0°. Cleavage occurs by initial sulfoxide reduction followed by acidolysis. ... 

Saturation of the aromatic ring of pentopril analogues is also consistent with ACE inhibition as demonstrated by the oral activity of indolapril (23). The necessary heterocyclic component (21) can in principle be prepared by catalytic perhydrogenation (Rh/C, HOAc) of the corresponding indole. A single isomer predominates. The product is condensed by amide bond formation with the appropriate alanylhomophenylalanyl dipeptide ester 20 to give 22. Selective saponification to 23 could be accomplished by treatment with HCl gas. Use of the appropriate stereoisomers (prepared by resolution processes) produces chiral indolapril [8]. 

Molecules of interest that contain free amino groups can be coupled in aqueous solution to /S-poIy(L-malate) as amides using carbodiimides such as the water-soluble l-ethyl-3(3-dimethyIaminopropyl)carbodiimide hydrochloride (EDC) [2,12,20,21]. By this method, the molecules are attached randomly. A selective amide bond formation at the carboxylate terminus can be achieved... 

Cyclic structures can form as a result of side reactions. One of the most common examples is the formation of diketopiperazines during the coupling of the third amino acid onto the peptide chain (Fig. 7). Intramolecular amide bond formation gives rise to a cyclic dipeptide of a six-membered ring structure, causing losses to the sequence and regeneration of the hydroxyl sites on the resin. The nucleophilic group on the resin can lead to fiuther unwanted reactions [14]. 

Initial Strategy-Amide Bond Formation as the Final Step... 

Use of an expensive coupling reagent to promote the amide bond formation A long-term cost implication... 

Oie, T., G. H. Loew, S. K. Burt, J. S. Binkley, and R. D. MacElroy. 1982. Ab Initio Study of Catalyzed and Uncatalyzed Amide Bond Formation as a Model for Peptide Bond Formation Ammonia-Formic Acid and Ammonia-Glycine Reactions. Int. J. Quantum Chem. Quantum Biol. Symp. 9, 223-245. 

SCHEME 58. First poly(propyleneimme) glycodendrimers (PPI) coated with thioglycosides through amide bond formation.417... 

Ring Opening with Amide Bond Formation... 

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