Carboxylic acid p-nitrophenyl esters

Peptides from carboxylic acid p-nitrophenyl esters COOAr CON<... 

Carboxylic acid aryl esters from carboxylic acids and aryl trifluoroacetates Carboxylic acid p-nitrophenyl esters Retention of optical activity... 

Carboxylic acid p-nitrophenyl esters COOH -> COOAr... 

In the second major method of peptide synthesis the carboxyl group is activated by converting it to an active ester, usually a p-nitrophenyl ester. Recall from Section 20.12 that esters react with ammonia and amines to give fflnides. p-Nitrophenyl esters are much more reactive than methyl and ethyl esters in these reactions because p-nitrophenoxide is a better (less basic) leaving group than methoxide and ethoxide. Simply allowing the active ester and a C-protected amino acid to stand in a suitable solvent is sufficient to bring about peptide bond formation by nucleophilic acyl substitution. 

The amino acid attached to a polymer is treated with an vV-protected, carboxyl-activated amino acid to give the supported peptide. In the following reaction the triazolide was formed in situ from the p-nitrophenyl ester and 1,2,4-triazole 1341... 

Histidine residues are efficient nucleophiles in aqueous solution at pH 7, much more so than lysines, and this is the basis for the site-selective functionalization of lysine residues in folded polypeptides and proteins [24, 25]. p-Nitrophenyl esters react with His residues in a two-step reaction to form an acyl intermediate under the release of p-nitrophenol followed by the reaction of the intermediate with the most potent nucleophile in solution to form the reaction product. In aqueous solution the reaction product is the carboxylic acid since the hydroxide ion is the most efficient nucleophile at pH 7. If there is an alcohol present the reaction product will be an ester and the overall reaction is a transesterification reaction. 

The ester-amine reaction is slow and requires long reaction times (see Chapter IV). Many active carboxylic acid derivatives such as the azides, p-nitrophenyl esters, and thiazolidine-2-thiones as well as carboxylic acid activators, such as dicyclohexylcarbodimide (DCCI), have been used to improve this reaction (see Chapter IV) (Kimura et al., 1989a, 1989b Krakowiak et al., 1989, 1990a Nagao et al., 1980, 1981 Uoto et al., 1990). These cyclization reactions seldom need high-dilution conditions. Even though ex-... 

Won et al. [19], have reported synthesis of polyesters with valine, leucine, isoleucine, methionine, and phenylalanine (Table 12.1). This three-step process involves synthesis of a diester and a dinitro compound that are copolymerized [19], An amino acid is first coupled with a diol (with 3, 4, or 6 methylene groups) in the presence of tosyl to yield a diester with acid salts of diamine at the terminal ends. The second monomer, di-p-nitrophenyl ester of carboxylic acids, is synthesized by a condensation reaction of adipoyl or se-bacoyl chloride with p-nitro phenol. The final polymerization step involves an arduous condensation reaction in the presence of a strong proton abstractor between acid salt of bis(amino acid-alkyne diester) and di-p-nitrophenyl ester of dicarboxylic acids. Following along the same lines, Chu and Guo [22] have copolymerized a mixture of nitro phenyl ester of succinate, adipate, or sebacate and nitrophenyl fumarate with toluenesulfonic acid salt of phenylalanine butane-1,4-diester. The addition of fumarate derivative to the monomer mixture provides an unsaturated double bond in the polymer backbone that can be functionalized for specific biomedical... 

Hexokinase, 287 Homoarginine, 552, 553 Homobiotinyl p-nitrophenyl ester, 615 Homoserino, 156, 414 Hydrazides as inhibitors, 38 test for, 211 Hydrazines, 210 synthesis of, 210 Hydrazones, test for, 211 Hydrocinnamaldehyde, 125 Hydrocinnamic acid, 123 Hydrofluoric acid, 201 Hydrogenation, 200 Hydrogen peroxide, 49-51, 315 Hydrophobic probes, 191 3/S-Hydroxy-5-androstene-17/S-carboxylic acid, 477... 

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