Amino acid ester hydrolysis

There are a few documented examples of studies of ligand effects on hydrolysis reactions. Angelici et al." investigated the effect of a number of multidentate ligands on the copper(II) ion-catalysed hydrolysis of coordinated amino acid esters. The equilibrium constant for binding of the ester and the rate constant for the hydrolysis of the resulting complex both decrease in the presence of ligands. Similar conclusions have been reached by Hay and Morris, who studied the effect of ethylenediamine... 

Simple esters cannot be allylated with allyl acetates, but the Schiff base 109 derived from o -amino acid esters such as glycine or alanine is allylated with allyl acetate. In this way. the o-allyl-a-amino acid 110 can be prepared after hydrolysis[34]. The Q-allyl-o-aminophosphonate 112 is prepared by allylation of the Schiff base 111 of diethyl aminomethylphosphonates. [35,36]. Asymmetric synthesis in this reaction using the (+ )-A, jV-dicyclohex-ylsulfamoylisobornyl alcohol ester of glycine and DIOP as a chiral ligand achieved 99% ec[72]. 

Enzymatic hydrolysis of A/-acylamino acids by amino acylase and amino acid esters by Hpase or carboxy esterase (70) is one kind of kinetic resolution. Kinetic resolution is found in chemical synthesis such as by epoxidation of racemic allyl alcohol and asymmetric hydrogenation (71). New routes for amino acid manufacturing are anticipated. 

The piperonyl ester can be prepared from an amino acid ester and the benzyl alcohol (imidazole/dioxane, 25°, 12 h, 85% yield) or from an amino acid and the benzyl chloride (Et3N, DMF, 25°, 57-95% yield). It is cleaved, more readily than a p-methoxybenzyl ester, by acidic hydrolysis (CF3COOH, 25°, 5 min, 91% yield). ... 

These transition metal carbenes, prepared in 66-97% yield from amino acid esters, are cleaved by acid hydrolysis (CF3CO2H, 20°, 80% yield 80% AcOH M = W BBr3,-25°). ... 

Amino acid esters act as chelates to Co111 for example, the /3-alanine isopropyl ester is known as both a chelate and as an /V-bonded monodentate,983 and the mechanism of hydrolysis of the ester, which is activated by coordination, to yield chelated /3-alanine has been closely examined. 

It is now almost 50 years since Kroll (41) first reported that hydrolysis rates of amino acid esters were accelerated by the addition of certain divalent transition metal ions. His observations prompted numerous studies in this area, but even today exact descriptions of these... 

The Co(III) center is generally regarded as lacking the polarizing power of a proton but its attachment to the N-terminus of an amino acid ester, as in [Co(NH3)5(GlyOEt)]3, accelerates OH -catalyzed hydrolysis by ca. 100-fold. This is similar to the effect observed for N-protonation. 

Rate Constants (km0, kon) for Intermolecular Hydrolysis of Some Free and Co(III)-Chelated Amino Acid Esters at 25°C, I = 1.0 M... 

In 1990, Choudary [139] reported that titanium-pillared montmorillonites modified with tartrates are very selective solid catalysts for the Sharpless epoxidation, as well as for the oxidation of aromatic sulfides [140], Unfortunately, this research has not been reproduced by other authors. Therefore, a more classical strategy to modify different metal oxides with histidine was used by Moriguchi et al. [141], The catalyst showed a modest e.s. for the solvolysis of activated amino acid esters. Starting from these discoveries, Morihara et al. [142] created in 1993 the so-called molecular footprints on the surface of an Al-doped silica gel using an amino acid derivative as chiral template molecule. After removal of the template, the catalyst showed low but significant e.s. for the hydrolysis of a structurally related anhydride. On the same fines, Cativiela and coworkers [143] treated silica or alumina with diethylaluminum chloride and menthol. The resulting modified material catalyzed Diels-Alder reaction between cyclopentadiene and methacrolein with modest e.s. (30% e.e.). As mentioned in the Introduction, all these catalysts are not yet practically important but rather they demonstrate that amorphous metal oxides can be modified successfully. 

Yang C, Gao H, Mitra AK (2001) Chemical stability, enzymatic hydrolysis, and nasal uptake of amino acid ester prodrugs of acyclovir. J Pharm Sci. 90 617-624. 

N. M. Mahfouz, M. A. Hassan, Synthesis, Chemical and Enzymatic Hydrolysis, and Bioavailabihty Evaluation in Rabbits of Metronidazole Amino Acid Ester Prodrugs with Enhanced Water Solubility , J. Pharm. Pharmacol. 2001, 53, 841-848. 

H. Bundgaard, C. Larsen, P. Thorbek, Prodrugs as Drug Delivery Systems XXVI. Preparation and Enzymatic Hydrolysis of Various Water-Soluble Amino Acid Esters of Metronidazole , Int. J. Pharm. 1984, 18, 61-11. 

C. Yang, H. Gao, A. K. Mitra, Chemical Stability, Enzymatic Hydrolysis, and Nasal Uptake of Amino Acid Ester Prodrugs of Acyclovir ,. /. Pharm. Sci. 2001, 90, 617-624. 

Novozymes, a subtilisin produced by Bacillus licheniformis, was used by Chen et al ° to carry out a dynamic kinetic resolution of benzyl, butyl, or propyl esters of DL-phenylalanine, tyrosine, and leucine. The hydrolysis was performed at pH 8.5 in 2-methyl-2-propanol/water (19 1) and the freed L-amino acids precipitated. The key feature bringing about continual racemization of the remaining D-amino acid esters was the inclusion of 20 mmol 1 pyridoxal phosphate. 

The discovery that metal ions such as Cu catalyzed the hydrolysis of amino acid esters was first reported nearly 40 years ago. Table 6.3 shows that in the absence of direct interaction of the ester grouping with the metal ion, the primary cause of any increased rates experienced... 

Table 6.3 Effect of Metal Coordination on Rate Constants for Base Hydrolysis of Amino Acid Esters at 25 °C...

A semi-synthetic metalloenzyme that catalyses the enantioselective hydrolysis of simple amino acid esters has been reported. Iodoacetamido-l,10-phenanthroline (238) was interacted with a cysteine residue in adipocyte lipid binding protein (ALBP) to produce the conjugate ALBP-Phen (239), which was converted into its Cu(II) complex. The ALBP-Phen-Cu(II) was found to catalyse the enantioselective... 

Metal-ion catalysis has been extensively reviewed (Martell, 1968 Bender, 1971). It appears that metal ions will not affect ester hydrolysis reactions unless there is a second co-ordination site in the molecule in addition to the carbonyl group. Hence, hydrolysis of the usual types of esters is not catadysed by metal ions, but hydrolysis of amino-acid esters is subject to catalysis, presumably by polarization of the carbonyl group (KroU, 1952). Cobalt (II), copper (II), and manganese (II) ions promote hydrolysis of glycine ethyl ester at pH 7-3-7-9 and 25°, conditions under which it is otherwise quite stable (Kroll, 1952). The rate constants have maximum values when the ratio of metal ion to ester concentration is unity. Consequently, the most active species is a 1 1 complex. The rate constant increases with the ability of the metal ion to complex with 2unines. The scheme of equation (30) was postulated. The rate of hydrolysis of glycine ethyl... 

This unnatural acid is used as a chiral intermediate for the synthesis of a number of products. Chemical asymmetric synthesis was very difficult and so the stereoselective synthetic properties of enzymes were exploited to carry out a selective reduction reaction. The stereoselective hydrolysis of protein amino acid esters had already been commercialised by Tanabe in Japan using immobilised aminoacylase, and selective reduction reactions using whole yeast cells are already used in a number of processes, such as the selective reduction of the anti-cancer drag Coriolin. 

Reactions of the ligand which are very slow in the absence of an electron pair acceptor or metallic coordination center. Basic hydrolysis of amino acid esters is an example of such a reaction. 

Generalized Rate Equations. This last reaction is typical of a large class of reactions which may proceed simultaneously by several parallel paths. The rate can be expressed as the sum of several contributions from the uncatalyzed and catalyzed paths. The overall rate for the hydrolysis of an amino acid ester in the presence of a metal salt may be expressed as... 

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