Carboxylic protecting groups for

Developed as a carboxyl protective group for peptide synthesis because of its stability to hydrogenolysis and acidic conditions, the acetol (hydroxy acetone) ester is prepared by DCC coupling (68-92% yield) of the acid with acetol. It is cleaved with TBAF in THF. ... 

Briand, B., Kotzur, N., Hagen, V. and Beyermann, M. (2008) A new photolabile carboxyl protecting group for native chemical ligation. Tetrahedron Letters, 49, 85-87. 

To direct the synthesis so that only Phe Gly is formed the ammo group of phe nylalanme and the carboxyl group of glycine must be protected so that they cannot react under the conditions of peptide bond formation We can represent the peptide bond for matron step by the following equation where X and Y are amine and carboxyl protecting groups respectively... 

Fig. 23. Representative protecting groups for phenolic and carboxylic acid-based systems, (a) The polymer-based protecting groups are fisted in order of increasing activation energy for acid-catalyzed deprotection, (b) Acid-labile monomeric dissolution inhibitors, a bifunctional system based on protected bisphenol A. (c) Another system that combines the function of dissolution inhibitor and PAG in a single unit.

See also Chapter 5, on the preparation of esters as protective groups for carboxylic acids. 

The phenyl group became a practical protective group for carboxylic acids when Sharpless published a mild, effective one-step method for its conversion to a carboxylic acid. It has recently been used in a synthesis of the amino acid statine, where it served as a masked or carboxylic acid equivalent. ... 

Carbamates can be used as protective groups for amino acids to minimize racem-ization in peptide synthesis. Racemization occurs during the base-catalyzed coupling reaction of an A-protected, carboxyl-activated amino acid and takes place in the intermediate oxazolone that forms readily from an A-acyl-protected amino acid (R = alkyl, aryl) ... 

The benzyloxycarbonyl protecting group for amines is introduced in high yield using benzyl imidazole-carboxylate with a catalytic amount (5%) of dimethylamino-pyridine.[1953... 

Scheme 8.5. Enzyme-triggered fragmentation of protective groups for amines, alcohols and carboxylic acids.

Piloto AM, Rovira D, Costa SPG, Gonfalves MST (2006) Oxobenzo[/]benzopyrans as new fluorescent photolabile protecting groups for the carboxylic function. Tetrahedron 62 ... 

The rearrangement of isopent-3-enyl epoxy esters with Cp2ZrCl2/AgC104 yields ABO esters (2,7,8-trioxabicyclo[3.2.1]octane Asymmetric Bicyclo-Octane esters), which are base-stable protecting groups for carboxylic acids [57,79,80] (Scheme 8.40). 

To overcome these difficulties in the selective deprotection and chain extension, several carboxyl-protecting groups, namely, allyl (16,32), benzyl (43,44), tert-butyl (42), 2-bromoethyl (45), 2-chloroethyl (45), heptyl (46), 4-nitrophenyl (47,48), and pentafluorophenyl (49) for L-serine/L-threonine have been introduced or applied. Similarly, amino-protecting groups for L-serine/L-threonine that have proved useful for the synthesis of glycopeptides are tm-butyloxycarbonyl (50), 9-fluorenylmethoxycarbonyl (43,44,48), 2-(2-pyridyl)ethoxycarbonyl (51), 2-(4-pyridyl)ethoxycarbonyl (44,52), and 2-triphenylphosphonioethoxycarbonyl (53). Some applications of these groups have been discussed in earlier reviews (7-11). 

Different Amino and Carboxyl Protecting-Group Combinations of L-Serine/L-Threonine Used for Glycopeptide Chain-Lengthening... 

A Karsltrom, A Unden. Design of protecting groups for the P-carboxylic group of aspartic acid that minimize base-catalyzed aspartimide formation, (dimethylpentyl) Int J Pept Prot Res 48, 305, 1996. 

F Albericio. Orthogonal protecting groups for V-amino and C-terminal carboxyl functions in solid-phase peptide synthesis. Biopolymers (Pept Sci) 55, 123-139, 2000. 

Ester formation is the main and most efficient means of protecting carboxylic acids. The protection of a carboxylic acid as an amide is infrequent, as its removal normally requires drastic conditions. Most of the work concerned with the use of light-sensitive protecting-groups for carboxylic acids is in peptide synthesis. Carboxylic acids are protected as photosensitive esters, including ester linkages to polymer supports or as (difficult to prepare) photosensitive amides. Many of these techniques may be readily applied to sugar acids. 

DinitrobenzenesuIfenic esters were proposed as protecting groups for carboxyl groups.The solvolysis of only a small variety of esters was studied with a high-pressure mercury lamp, and the yields were 88-98% (see Scheme 26). It should be noted, however, that the group is particularly sensitive to hydrolysis and ammonolysis. 

Fig. 2.—Nitroanilides Employed as Protecting Groups for Carboxylic Acids.

The allyl group, a less familiar protective group for carboxylic acids, can be easily removed from esters by treatment with sodium hydrogen telluride. In contrast to the preceding methods, ethanol has been employed as the solvent. 

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