Carboxyl group protection

Base-catalyzed hydrolysis is employed primarily for the liberation of carboxyl groups protected as esters. The reaction involves direct attack by the hydroxide anion... 

M Meldal, B Klaus. Pentafluorophenyl esters for temporary carboxyl group protection in solid phase synthesis of A-linked glycopeptides. Tetrahedron Lett 48, 6987, 1990. 

Many different approaches have been developed for peptide synthesis, and it is not the intention to cover more than the basic principles here, with a suitable example. The philosophy to convert two amino acids into a dipeptide is to transform each difunctional amino acid into a monofunctional compound, one of which has the amino group protected, whilst the other has the carboxyl group protected. This allows... 

Thus, according to Scheme 28, (-)-shikimic acid 169 was converted to cyclohexadiene derivative 170 via esterification of carboxyl group, protection of the m-disposed hydroxyls, and elimination of the remaining carbinol moiety. Catalytic dihydroxylation of 170 gave unsaturated esters 171 and 172 as a separable 1 1 mixture. The 5,5a-unsaturated isomer 171 was finally elaborated into the desired (-)-MK7607 (174) via simple protection-reduction-deprotection sequence. 

This is done as described in Subheading 3,1,1, but using the eventual penultimate residue of the peptide target with its carboxyl group protected as an allyl or ferf-butyl ester. 

Carboxyl group protection. Carboxylic acids are derived into the amides using... 

Saponification. In the context of carboxyl group protection, the derivatization into base-stable amides with 2-(2-aminophenyl)acetaldehyde dimethyl acetal can be considered. Regeneration is via the Al-acylindoles (which are formed by a PPTS-catalyzed cyclization) and treatment of the latter compounds with LiOH-I Oj in aqueous THF. 

Photoreleasable esters. A method for carboxyl group protection is based on esters obtained by O-alkylation of acids with the phenacyl chloride. The photochemical decomposition that regenerates the acids does not require a photosensitizer. 

Carboxyl group protection. The a -esters of aspartic and glutamic acids are formed readily using the DCC method, after the geminal functionalities are sequestered (by reaction with EtiB). The acid can be regenerated under conditions lO.l M BU4NF) that do not affect an N-Boc group. 

Side chain lithiation is a major source of reactivity in terms of the elaboration of pyrroles and indoles, and new examples and developments continue to be reported. One major development has been the lithiation of 2-alkyl groups of 2-alkylindole-1 -carboxylate lithium salts. The carboxyl group protects the nitrogen atom, directs the lithiation, and can easily be removed after alkylation (Scheme 121) <86JA6808>. Similarly, lithiation of 2,3-dialkylindoles takes place at the 2-methylene position via the C,7V-dilithio derivative, using three equivalents of butyllithium <9UOC2256>. 

The Strategy of Peptide Synthesis 1147 Amino Group Protection 1148 Carboxyl Group Protection 1151 Peptide Bond Formation 1151 Solid-Phase Peptide Synthesis ... 

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