Methyl glycinate, hydrolysis

Table 4 Rate Constants for the Metal Ion-promoted Hydrolysis of Methyl Glycinate and Ethyl Glycinate...

Table 6 Activation Parameters for the Hydrolysis of Methyl Glycinate in the Presence of Metal Nitriloacetates and Tetradentate Nickel(ll) Chelates at 1 = 0.1 M ...

Table 7 Rate Constants (kOH) and Equilibrium Constants (log KCuL) Associated with the CuL-promoted Hydrolysis of Methyl Glycinate at 25 °C...

Table 3-1. Rate constants for the hydrolysis of methyl glycinate, H2NCH2C02Me, in neutral water, in dilute acid and in the presence of copper(n) salts.

Creatinase catalyzes the hydrolysis of creatine to N-methyl-glycine and urea by a mechanism in which water is activated for attack on substrate guanidinium carbon by the imidazole of His acting as general base [66]. 

With aqueous methanol in the presence of hydrochloric acid, hydrolysis of 73 took place to give enol 74, while with N-nucleophiles such as methyl glycinate, aniline, 4-methylaniline and 4-nitoaniline in methanol containing hydrochloric acid at room temperature, substitution products 75 were formed in relatively good yields (Scheme 25). 

For methyl glycinate at 25°C, ko - is 7.6 x 10 M s and k for water attack is 4.3 x 10 s. The observed first order rate constant for water attack can be converted to a second order rate constant by dividing by the molar concentration of water OChk) = k/55.5 = 7.7 X 10 M s ). The ratio Icoh- hjo = 10" and is a measure of the relative nucleophilicities of hydroxide ion and water towards the copper complex. The ratio kou-/kg = 7.6 X lOVl.28 10 and this is within the normal range of rate enhancements (10 -10 fold) observed for copper(II) promoted hydrolysis of carboxylic esters where copper(II) interacts directly with the alkoxycarbonyl group of the ester. 

Solvolysis of Organic Ligands.— The catalysis of hydrolysis of organic esters by metal ions or complexes has been much studied for many years. Recent examples of kinetic studies include hydrolysis of oxalate esters catalysed by a variety of ions, and of the bis[-L-(-J-)-histidine methyl ester] complexes of copper(n) and of nickel(n). The relative catalytic effects of several copper(n) complexes, including Cu(imda), Cu(nta), and Cu(dien) +, on the hydrolysis of methyl glycinate have been determined. Rate constants for base hydrolysis of this ester correlate with stability constants for mixed complexes of this ester with the above-named copper(n) complexes. ... 

GME glycine methyl ester GDM glutamic dimethyl ester EDA ethylendiamine GAM glucosamine HDA hexadecylamine BSA bovine serum albumin OVA ovalbumin CA carbonic anhydrase MYO myoglobin H alkaline hydrolysis for converting ester groups from GME or GDM into free carboxylic acid groups that were subsequently activated with EDC for further modifications. 

A- [(Acy loxy )methyl] derivatization was also examined for its potential to improve the biological stability of peptides. For example, the peptide-like model A-[(benzyloxy )carbonyl]glycine benzylamide (8.171, R = H) was de-rivatized to a few N-/Yacyloxy)methyl] derivatives whose chemical and enzymatic hydrolysis was investigated [225], The results compiled in Table 8.13 indicate a fast chemical hydrolysis, the mechanism of which is depicted as Reaction b in Fig. 8.21. Enzymatic hydrolysis also occurs in human plasma, resulting in short half-lives, with the exception of the pivaloyl analogue. 

Several syntheses of muraghtazar (3) have appeared in patents (Cheng et al.) and journals (Devasthale et al., 2005) (Scheme 8.3). Alkylation of 4-hydroxybenzaldehyde with the phenyloxazolemesylate 23, prepared readily from commercially available alcohol 22, yielded aldehyde 24, which was treated with glycine methyl ester under reductive amination conditions to provide secondary amine 25 in excellent yield. Reaction of amine 25 with 4-methoxyphenyl chloroformate followed by hydrolysis of the methyl ester afforded 3 in 94% yield. 

The synthesis of losartan potassium (1) by the process research chemists at Merck is outlined in the following (Griffiths et ak, 1999 Larsen et al., 1994). Phenyltetrazole (8) is protected as the trityl phenyltetrazole 9 (Scheme 9.3). Ortho-lithiation of 9 followed by quenching with triisopropyl borate afforded boronic acid 10 after treatment with aqueous ammonium chloride. Reaction of glycine (11) with methyl pentanimidate (12) in a methanol/water mixture yielded (pentanimidoylamino) acetic acid (13), which underwent a Vilsmeier reaction with phosphorous oxychloride in DMF followed by hydrolysis to give imidazole-4-carbaldehyde 14 in moderate yield. 

Table II. Effect of Several Metal Ions on Hydrolysis of Glycine Methyl Ester (28)...

Detailed kinetic studies revealed that glycine methyl ester and phenylalanine methyl ester in glycine buffer at pH 7.3 undergo a facile hydrolysis catalyzed by cupric ion (11). Under these conditions the reactions closely follow a first-order rate law in the substrate. Using these kinetic data it is possible to compare the rates of hydrolysis of DL-phenylalanine ethyl ester as catalyzed by hydronium, hydroxide, and cupric ion (see Table III). 

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