Amino acid amides hydrolysis

The industrial process for preparing the reagent usually permits a little hydrolysis to occur, and the product may contain a little free calcium hydroxide or basic chloride. It cannot therefore be employed for drying acids or acidic liquids. Calcium chloride combines with alcohols, phenols, amines, amino-acids, amides, ketones, and some aldehydes and esters, and thus cannot be used with these classes of compounds. 

Racemic a-amino amides and a-hydroxy amides have been hydrolyzed enantio-selectively by amidases. Both L-selective and o-selective amidases are known. For example, a purified L-selective amidase from Ochrobactrum anthropi combines a very broad substrate specificity with a high enantioselectivity on a-hydrogen and a,a-disubstituted a-amino acid amides, a-hydroxyacid amides, and a-N-hydroxya-mino acid amides [102]. A racemase (a-amino-e-caprolactam racemase, EC 5.1.1.15) converts the o-aminopeptidase-catalyzed hydrolysis of a-amino acid amides into a DKR (Figure 6.38) [103]. 

Table 6w4 Effect of Cobalt(lll) Coordination on Rate Constants for Base Hydrolysis of Amino Acid Amides...

This zinc-dependent enzyme [EC 3.4.11.1], also referred to as cytosol aminopeptidase, leucyl aminopeptidase, and peptidase S, catalyzes the hydrolysis of a terminal peptide bond such that there is a release of an N-terminal amino acid, Xaa-Xbb-, in which Xaa is preferably a leucyl residue, but may be other aminoacyl residues including prolyl (although not arginyl or lysyl). Xbb may be prolyl. In addition, amino acid amides and methyl esters are also readily hydrolyzed, but the rates with arylamides are exceedingly slow. The enzyme is activated by heavy metal ions. 

A particularly interesting case is the partial hydrolysis of the racemic N-tri-fluoroacetyl derivative 59 with hog kidney aminoacylase (HKA) (EC 3.5.1.14) to prepare chiral isomers of 2-trifluoromethylalanine 60 [53]. The stereochemical preference of hog kidney aminoacylase is to hydrolyze amino acid amides bearing the larger C-2 substituent in the pro-S position [54]. The enzymatic hydrolysis of compound 60 follows this trend. 

Amides. Metal ions catalyze the hydrolysis of a variety of amides, including acylamino acids, dipeptides and tripeptides, and amino acid amides. In all these compounds it is possible for a metal ion to complex with one or more ligand groups, either amine or carboxylate ion functions, in addition to the amide group. Thus the structural prerequisites for the metal ion catalysis of amide hydrolysis are the same as those for ester hydrolysis. 

The degradation of support-bound a-amino acid amides has been used to prepare retro-inverso peptide mimetics ([226], second equation in Figure 10.6). These compounds are of interest because of their potentially improved metabolic stabilities, selectivities, and biological activities compared with peptides [226], Although retro-inverso peptides are aminals susceptible to acid-catalyzed hydrolysis, N,N -diacylated aminals can be sufficiently stable to withstand the conditions of Boc-group removal [227] or of acidolytic cleavage of peptides from Wang resin [226]. 

One reason for an otherwise apparently excessive interest in Co(trien)X2+ systems is the use of ds-Co(OH)(trien)(OH2)2+ in the hydrolysis of amino acid esters, amino acid amides and peptides785 to form cis-px- and cis-/J2-Co(trien)(aa)2+ (aa = amino acid) complexes.16 In principle, a peptide could be degraded in a stepwise manner and each amino acid residue successively characterized. By the introduction of a chiral center into the backbone of the trien moiety, it was hoped to make such reactions stereoselective. Consequently, while fully A-alkylated trien systems have been widely investigated for M11 central ions, the C-alkylated trien systems have been almost exclusively the reserve of the Co111 chemist (Table 11). 

Figure 3-10. Hydrolysis of an amino acid amide (peptide).

When we consider the reverse reactions, the metal-directed hydrolysis of amides, the polarising metal ion may also play a second, and often undesirable, role. In addition to polarising the carbonyl group and activating the carbon atom to nucleophilic attack, the metal may also polarise an amide N-H bond. If we consider the amino acid amide 3.4, the polarisation may be transmitted through the ligand framework to the amide N-H bond. This polarisation may be sufficient to lower the pKa so as to allow deprotonation under the desired reaction conditions (Fig. 3-13). 

Although the above discussion has concentrated upon the hydrolysis of amino acid esters, very similar mechanisms have been demonstrated for the hydrolysis of amino acid amides. A very wide range of intramolecular reactions of this type are now known to occur by intramolecular attack by hydroxide, with most having been demonstrated at non-labile... 

Figure 7 Preparation of chiral synthon for (3-3-receptor agonist (A) enzymatic resolution of racemic amino acid amide (8) by amidase from M. neoaurum ATCC 25795 (B) enzymatic resolution of racemic amino acid amide (10) by amidase from M. neoaurum ATCC 25795 (C) enzymatic asymmetric hydrolysis of diester (12) to the corresponding (>S)-monoester (13) by pig liver esterase.

I. A. Yamskov, T. V. Tichonova, V. A. Davankov, Pronase-catalyzed hydrolysis of amino acid amides, Enzyme Microb. Tech., 8 (1986), 241-244. 

Boesten, W.H.J. and Cals, M.J.H. 1987. Process for the enzymatic hydrolysis of d-a-amino-acid amides. US Patent 4 705-52. 

Co(trien)(NH3)2] + has been isolated, and only the meso trans isomers (197-198) with two different axial ligands, remain to be distinguished. There is also an extensive chemistry of N and C-alkylated derivatives of (178 180) as cA-[Co(OH)(trien)(OH2)] assists the hydrolysis of amino acid esters, amino acid amides, and peptides to form cis-fi (194) and cA-jS2-[Co(OA0(trien)] + (195)(( A = amino acid) complexes. Chiral alkylated trien ligands have the potential for chiral stereospecificity in such reactions. 

DSM has developed a widely applicable industrial process for production of en-antiomerically pure amino acids by enantioselective hydrolysis of racemic amino acid amides. These precursor compounds can easily be obtained by alkaline... 

D- and L-Amino acids (miscellaneous) by amino acid amide hydrolysis L-specific amidase... 

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