2- ethyl esters protect carboxyl groups

Methyl and ethyl esters of carboxylic acids are successfully cleaved with bis(tri- -butyltin) oxide to give the free carboxylic acids even in the presence of other functional groups and/or protecting groups (Equation (94)).257... 

Trimethylsilyl)ethyl esters, to protect carboxyl groups, 242... 

The amino group in Z-Ala is protected as the nonnucleophilic amide half of a carbamate ester. The carboxyl group can be activated without reacting with the protected amino group. Treatment with ethyl chloroformate converts the carboxyl group to a mixed anhydride of the amino acid and carbonic acid. It is strongly activated toward nucleophilic attack. 

For protecting carboxyl groups, methyl esters (OMe), ethyl esters (OEt), benzyl esters (OBZL), p-nitrobenzyl esters (ONB), /-butyl esters (OBut) or substituted hydrazides (e.g., —N2H2—Z) are used. Coupling occurs according to the azide method. 

Carboxyl groups of ammo acids and peptides are normally protected as esters Methyl and ethyl esters are prepared by Fischer esterification Deprotection of methyl and ethyl esters is accomplished by hydrolysis m base Benzyl esters are a popular choice because they can also be removed by hydrogenolysis Thus a synthetic peptide protected at both... 

Section 27 16 Carboxyl groups are normally protected as benzyl methyl or ethyl esters Hydrolysis m dilute base is normally used to deprotect methyl and ethyl esters Benzyl protecting groups are removed by hydrogenolysis... 

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. 

Section 27.16 Carboxyl groups are normally protected as benzyl, methyl, or ethyl esters. 

In a penicillin synthesis, the carboxyl group was protected as a / -bromophenacyl ester that was cleaved by nucleophilic displacement (PhSK, DMF, 20°, 30 min, 64% yield). Hydrogenolysis of a benzyl ester was difficult (perhaps because of catalyst poisoning by sulfur) basic hydrolysis of methyl or ethyl esters led to attack at the /3-lactam ring. ... 

Furthermore, attempted cyclization of N-carboxymethyl meroquinene ethyl ester failed to afford any of the enone, suggesting that the carboxylic acid was an intermediate. The N-protecting groups, in addition to benzoyl, that are tolerated include CC Me, pivaloyl, acetyl, toluenesulfonyl, CBz, and alkyl. 

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