Activated Esters Properties and Specific Uses

Most activated esters are crystalline compounds that can be stored for subsequent use. A variety of properties are exhibited by the various esters. All esters mentioned in this monograph (see Section 2.9) except succinimido esters generate a hydroxy compound that is insoluble in water when aminolyzed. Elimination of this material can be a nuisance in some cases. Nitrophenols are not readily soluble in alkali a trace is sufficient to produce a yellow color in the solution of the reaction product. 

FIGURE 7.14 Activated esters for temporary protection and activation of Fmoc-amino acids for the synthesis of glycopeptides. (A) Reaction of a-D-glucopyranosyl bromide with esterified Fmoc-serine. (B) Reaction of 2-acetamido-2-deoxy-3,4,6-triacetyl- 3-D-glucopyranosyl amine with esterified Fmoc-aspartyl chloride.37-38 Pfp = pentafluorophenyl. 

Halophenols are easier to dispose of by extraction. Chlorophenyl esters are resistant to hydrogenation and are hence compatible with benzyloxycarbonyl. Benzotriazolyl esters are unique in that they exist in two different forms (see Section 7.17). They are too reactive for routine use but are often employed without isolation after their preparation, using a carbodiimide or other (see Section 7.20). An exception to this are the benzotriazolyl adducts of. V-lrilylamino acids that are amide oxides (see Section 7.17), which are stable to aqueous sodium hydroxide but undergo aminolysis normally. 

FIGURE 7.15 Aminolysis of 4-oxo-3,4-dihydrobenzotriazin-3-yl esters produces a yellow color, the intensity of which is a measure of the number of amino groups present. The color disappears when the amino groups have been consumed. 

M Bodanszky, V duVigneaud. A method of synthesis of long peptide chains using a synthesis of oxytocin as an example. J Am Chem Soc 81, 5688, 1959. 

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