Acid Protecting Groups

If only the O-H, as opposed to the carbonyl, of a carboxyl group has to be masked, it can be readily accomplished by esterification. Alkaline hydrolysis is the usual way for regenerating the acid. t-Butyl esters, which are readily cleaved by acid, can be used if alkaline conditions must be avoided. 2,2,2-Trichloroethyl esters, which can be reductively cleaved with zinc, are another possibility.267 Some esters can be cleaved by treatment with anhydrous TBAF. These reactions proceed best for esters of relatively acidic alcohols, such as 4-nitrobenzyl, 2,2,2-trichloroethyl, and cyanoethyl.268 

The more difficult problem of protecting the carbonyl group can be accomplished by conversion to a oxazoline derivative. One example is the 4,4-dimethyl derivative, which can be prepared from the acid by reaction with 2-amino-2-methylpropanol or with 2,2-dimethylaziridine.269 

The heterocyclic derivative successfully protects the acid from attack by Grignard or hydride-transfer reagents. The carboxylic acid group can be regenerated by acidic hydrolysis or converted to an ester by acid-catalyzed reaction with the appropriate alcohol. 

Carboxylic acids can also be protected as orthoesters. Orthoesters derived from simple alcohols are very easily hydrolyzed, and the 4-methyl-2,6,7-trioxabicyclo[2.2.2]octane structure is a more useful orthoester protecting group. These 

The latter method is improved by use of the 2,2-dimethyl derivative.273 The rearrangement is faster and the stability of the orthoester to hydrolysis is better. Isotopic labeling showed that the rearrangement occurs by ionization at the tertiary position. 

Lactones can be protected as their dithioketals by using a method that is analogous to ketone protection. The required reagent is readily prepared from trimethylaluminum and ethanedithiol. 

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Oxazoles, prepared from carboxylic acids (benzoin, DCC NH4OAC, AcOH, BOSS % yield), have been used as carboxylic acid protective groups in a variety of synthetic applications. They are readily cleaved by singlet oxygen followed by hydrolysis (ROH, TsOH, benzene or K2CO3, MeOH ). 

The Paloc group was developed as an amino acid protective group that is introduced with the p-nitrophenyl carbonate (H2O, dioxane, 68-89% yield). It is exceptionally stable to TFA and to rhodium-catalyzed allyl isomerization, but it is conveniently cleaved with Pd(Ph3P)4 (methylaniline, THF, 20°, 10 h, 74-89% yield). ... 

An alternate route to ampicillin not only circumvents the need for 6-APA but also has the advantage of providing a prodrug form of ampicillin as well as the parent compound. Reaction of benzylpenicillin (4) with the acid protecting group, 29, gives the formol ester, 30. Reaction of the product with phosphorus pentachloride leads to the corresponding imino chloride (31). 

In 2002, Couturier and coworkers investigated the possibility of using a dioxazole as an aprotic hydroxamic acid protective group. In this context, the masked hydroxamic acid could be introduced earlier in the synthesis and could perhaps be released in a single operation at the end of the sequence. 

Amino Acid Protecting Groups Suitable for Solution Synthesis Protecting Groups Suitable for Solid-Phase Synthesis on HMFS Resin... 

If du Vigneaud and Bodanszky had wanted a carboxylic-acid-protecting group that was more stable towards attack by nucleophiles, they could have made a t-butyl ester with isobutene in sulfuric acid. 

Standard amino acid protecting groups that were used routinely in BOC-peptide synthesis. For Lys the -nitrogen has the potential to cyclize. We sometimes protect this with the fluorenylmethyloxycarbonyl (FMOC) protecting group. 

Amino acid-protecting groups such as benzyloxycarbonyl and t-butoxycarbonyl groups are cleaved by BBr3. 

Patrikeev et al. also employed imprinted silicas for thin layer chromatography. The silica was mixed with plaster and immobilised on a plate for use in the separation and identification of gramines [31] and for the resolution of amino acid derivatives [29]. In the latter experiment it was found that the influence of the amino acid protective group, dinitrophenol, was too dominant to allow the separation of... 

A more useful application of the electron-attracting effect of aryl subtituents is found in the cleavage of 4-picolyl derivatives of protected cysteine and tyrosine in peptide synthesis (Scheme 14).Catalytic cleavage of these derivatives is usually unattractive for SProtecting groups removable also include 3- and 4-picolyl esters. ... 

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