Amino esters, aliphatic hydrolysis

Many a-amino acid esters or related short-chained aliphatic amino esters show satisfying hydrolysis kinetics in plasma, but exhibit poor stability in aqueous solution. This poor stability is predominantly due to electron withdrawal by the positively charged amino group, but may also involve intramolecular catalysis or assistance of the ester hydrolysis by the neighboring amino group. The replacement of the glycine unit by its benzologue, as shown for... 

Recently, 9 (Figure 6.5) was shown to catalyze the biomimetic transformation of a-keto esters to a-amino acids with various functional groups [39]. The reaction is pictured in Scheme 6.17 as involving imine isomerization catalyzed by 9 prior to hydrolysis and the favored formation of the a-amino ester in the (R) configuration. Various phenylalanine derivatives could be obtained by this reaction. The reaction worked equally well for a-keto esters with an aromatic or aliphatic group and for esters with an ether or thioether function in addition to the a-carbonyl group. 

A convenient source of esterase for in vitro laboratory use is malt enzyme (diastase, J. P.) the application of which was described by Noguchi (N-672, N-673). Noguchi reported the successful hydrolysis of acetates at the IBa-, 17/3-, 20a-, 20/3-, and 21-positions (N-672). He also extended this method to 21-esters of other straight-chain aliphatic carboxylic acids (formate, butyrate, and caprylate), dibasic aliphatic hemiesters (hemisuccinate and hemitartrate) and JV-substituted amino acid esters (diraethylaminoacetate and diethylaminoacetate) (N-673). 17/3-Formate was hydrolyzed, t 17/3-propionate was not. 

NHS-esters react with primary amines to form a carboxamide and N-hydroxy-succinamide (see Figure 4.4). NHS-esters show reasonable reactivity and high selectivity towards aliphatic amines but can also react with aromatic amines, histidines and tyrosines, but at a significantly lower rate. In proteins, this practically limits the reactive groups to either the a -amino group of the N-terminus, or the s-amine of the lysine side-chain. In an aqueous environment the optimum pH for this reaction is 8.0-9.0. However, it should be noted that the rate of hydrolysis of succinimidyl esters increases with increasing pH (but is slow when [Pg.179]

Only a few rates of hydrolysis of aliphatic esters containing amino groups have been studied. Structural factors and reaction conditions are important in determining whether hydrolysis occurs through neighboring amino-group participation (see section V.A.2) or by... 

Protection for the Carboxy Group. Isobutene has been widely used in synthesis to convert carboxylic acids into corresponding t-butyl esters. t-Butyl esters of aliphatic acids (eq 1), aromatic carboxylic acids (eq 2), and A -protected amino acids (eq 3) have been prepared. The hindered r-butyl esters are stable to saponification but can be cleaved by acid-catalyzed hydrolysis, with liberation of isobutene. 

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