Glycine Methyl Ester Research Articles

Complex formation equilibria of palladium(II) complexes involving N, N′-dimethylethylenediamine, DNA constituents and cyclobutane dicarboxylic acid. The catalysis of glycine methyl ester hydrolysis through complex formation

Mixed-ligand complex formation equilibria of Pd(Me 2en)–CBDCA–DNA constituent have been investigated (Me 2en= N, N′-dimethylethylenediamine, CBDCA=cyclobutane dicarboxylic acid). The results show ring opening of CBDCA and monodentate complexation of the DNA constituent. Stoichiometries and stability constants of the complexes were determined at 25 °C and at constant 0.1 M ionic strength. The kinetics of base hydrolysis of glycine methyl ester in presence of Pd(Me 2en) 2+ complex was studied in aqueous solution at different temperatures, and in dioxane–water solutions of different compositions at 25 °C.

Ternary complexes involving copper(II) and amino acids, peptides and DNA constituents. The kinetics of hydrolysis of α-amino acid esters

Binary and ternary complexes of copper(II) involving picolylamine (Pic) and amino acids, peptides (HL) or DNA constituents have been investigated. Ternary complexes of amino acids or peptides are formed by simultaneous reactions. Amino acids form the Cu(Pic)L complex, whereas peptides form Cu(Pic)L and Cu(Pic)(LH−1). The ternary complexes of copper(II) with picolylamine and DNA are formed in a stepwise process, whereby binding of copper(II) to picolylamine is followed by ligation of the DNA components. The stability of the ternary complexes is compared with the stabilities of the corresponding binary complexes. The hydrolysis of glycine methyl ester (MeGly) is catalysed by the Cu(pic)2+ complex. The kinetic data is fitted assuming that the hydrolysis proceeds in two steps. The first step, involving coordination of the amino acid ester by the amino and carbonyl groups, is followed by rate-determining attack by the OH− ion. The second step involves equilibrium formation of the hydroxo-complex, Cu(pic)(MeGly)(OH), followed by intramolecular attack.

Synthesis and transformations of methyl (Z)-2-[(tert-butoxycarbonyl)amino]-3-(dimethylamino)propenoate

Methyl (Z)-2-((tert-butoxycarbonyl)amino)-3-(dimethylamino)propenoate (3) was prepared in 2 steps from glycine methyl ester hydrochloride (1). Acid catalysed reactions of 3 with various alkyl-, aryl-, and heteroarylamines 4a-g, performed at 20-80 °C, proceeded by substitution of the dimethylamino group giving the corresponding substitution products, 3-N-substituted methyl (Z)-2-((tert-butoxycarbonyl)-amino)amino)propenoates 5a-g. Treatment of 3 with ambident 1,3- nucleophiles, such as 2-pyridineacetonitrile (6), 2-aminothiazole (4d), 2-aminopyridine (4f), and 4-hydroxy-6-methyl-2H-pyran-3-one (7) in acetic acid at 85-120 °C afforded fused pyridones 8 and 12, pyrimidones 9 and 10 and pyranones 11 and 13.

Design, synthesis, photochemical properties and cytotoxic activities of water-Soluble caged l-Leucyl- l-leucine methyl esters that control apoptosis of immune cells

l-Leucyl- l-leucine methyl esters (LeuLeuOMe) is a lysosomotropic agent that induces apoptosis of certain immune cells. Glucose-carrying 2-nitrobenzyl (2-NB) and 2-nitrophenethyl (2-NPE) caged LeuLeuOMe, 1a and b, were synthesized and their photochemical and immunological properties were studied. Caged glycine methyl esters (GlyOMe), 2a, b, were also prepared to examine the cytotoxic activity of the photolytic byproducts from 1a, b. All the caged compounds were soluble in PBS containing 1% DMSO more than 400 μM, and efficiently released the substrates upon irradiation at 350 nm. While both 1a and 1b were not toxic to HL60 cells, 1b released LeuLeuOMe more quickly and induced apoptosis of HL60 cells far more efficiently than 1a. Although GlyOMe was not cytotoxic, 2a and b were slightly toxic before and after irradiation almost to the similar extent. Therefore, the photolytic products from the caging groups appear to be not toxic to the cells, and the apoptosis inducing activity of 1a and b may be for the most part due to LeuLeuOMe.

Sweetness and enzymatic activity of lysozyme.

Hen egg lysozyme elicits a sweet taste sensation for human beings. Effects of reduction of disulfide bonds, heat treatment, and chemical modification of hen egg lysozyme on both sweetness and hydrolytic activity were investigated. Both the sweetness and enzymatic activities were lost when the intradisulfide linkage in a lysozyme molecule was reduced and S-3-(trimethylated amino) propylated. The sweetness and enzymatic activity of lysozyme were lost on heating at 95 degrees C for 18 h. These facts suggest that tertiary structures of lysozyme are indispensable for eliciting a sweet taste as well as enzymatic activity. Although the modification of carboxyl residues in a lysozyme by glycine methylester or aminomethansulfonic acid resulted in the loss of enzymatic activity by blocking the catalytic residues, the sweetness was fully retained. These results indicate that the sweetness of lysozyme was independent of its enzymatic activity. The lysozyme purified from goose egg white similarly elicited a sweet taste, although goose (g-type) lysozyme is quite different from hen egg lysozyme (c-type) on the basis of structural, immunological, and enzymatic properties. These findings indicate that a specific protein property of lysozyme is required for sweetness elicitation and that the enzymatic activity and carbohydrates produced by enzymatic reaction are not related to the sweet taste.

Synthesis of ferrocene substituted pyrrolidine derivatives via Et 2Zn catalyzed 1,3-dipolar cycloaddition reactions of azomethine ylides

Synthesis of ferrocene substituted pyrrolidine derivatives via diethylzinc catalyzed 1,3-dipolar cycloadditions of azomethine ylides is described. Azomethine ylides were generated from glycine methyl ester and ferrocenecarboxaldehyde by the ‘imine tautomerization’ method and trapped with dipolarophiles to give the corresponding cycloadducts in reasonable yields and high regio- and stereoselectivity.

Glycine enolates: the large effect of iminium ion formation on alpha-amino carbon acidity.

Department of Chemistry, UniVersity at BuffaloSUNY, Buffalo New York 14260-3000Departamento de Qui´mica Fi´sica, Facultad de Qui´micaUniVersidad de Santiago15706 Santiago de Compostela, SpainReceiVed May 22, 2001ReVised Manuscript ReceiVed July 9, 2001We wish to report extraordinarily efficient catalysis of depro-tonation of the R-amino carbon of glycine methyl ester by thesimple ketone acetone that is the result of a 10

ClC-2 Cl- channels in human lung epithelia: activation by arachidonic acid, amidation, and acid-activated omeprazole.

ClC-2 Cl- channels represent a potential target for therapy in cystic fibrosis. Key questions regarding the feasibility of using ClC-2 as a therapeutic target are addressed in the present studies, including whether the channels are present in human lung epithelia and whether activators of the channel can be identified. Two new mechanisms of activation of human recombinant ClC-2 Cl- channels expressed in HEK-293 cells were identified: amidation with glycine methyl ester catalyzed by 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDC) and treatment with acid-activated omeprazole. ClC-2 mRNA was detected by RT-PCR. Channel function was assessed by measuring Cl- currents by patch clamp in the presence of a cAMP-dependent protein kinase (PKA) inhibitor, myristoylated protein kinase inhibitor, to prevent PKA-activated Cl- currents. Calu-3, A549, and BEAS-2B cell lines derived from different human lung epithelia contained ClC-2 mRNA, and Cl- currents were increased by amidation, acid-activated omeprazole, and arachidonic acid. Similar results were obtained with buccal cells from healthy individuals and cystic fibrosis patients. The ClC-2 Cl- channel is thus a potential target for therapy in cystic fibrosis.

Kinetic studies of guinea pig liver transglutaminase reveal a general-base-catalyzed deacylation mechanism.

Guinea pig liver transglutaminase (TGase) reacts with 0.1 mM N-Cbz-L-Glu(gamma-p-nitrophenyl ester)Gly (5, prepared herein, K(M) = 0.02 mM) to undergo rapid acylation that can be followed spectrophotometrically at 400 nm (pH 7.0, 25 degrees C). Deacylation of the transiently formed thiolester acyl enzyme intermediate via catalytic aminolysis was studied in the presence of six primary amines of widely varying basicity (pK(NH+) = 5.6-10.5). Steady-state kinetic studies were performed to measure k(cat) and K(M) values for each amine substrate. A Brønsted plot constructed through the correlation of log(k(cat)/K(M)) and pK(NH+) for each amine substrate displays a linear free-energy relationship with a slope beta(nuc) = -0.37 +/- 0.08. The shallow negative slope is consistent with a general-base-catalyzed deacylation mechanism in which a proton is removed from the amine substrate during its rate-limiting nucleophilic attack on the thiolester carbonyl. Kinetic isotope effects were measured for four acceptor substrates (water, kie = 1.1 +/- 0.1; aminoacetonitrile, kie = 5.9 +/- 1.2; glycine methyl ester, kie = 3.4 +/- 0.7; N-Ac-L-lysine methyl ester, kie = 1.1 +/- 0.1) and are consistent with a proton in flight at the rate-limiting transition state. The active site general-base implicated by these kinetic results is believed to be His-334, of the highly conserved TGase Cys-His-Asp catalytic triad.

Synthesis of highly substituted spiropyrrolidines via 1,3-dipolar cycloaddition reaction of N-metalated azomethine ylides

3-Arylidene-4-chromanones undergo regioselective 1,3-dipolar cycloaddition reactions with N-metalated azomethine ylides derived from aromatic aldimines of glycine methyl ester in the presence of silver acetate and triethylamine to give spiropyrrolidine derivatives in good yield. X-Ray crystal structure analysis of one of the products confirms the structure and regiochemistry of the cycloadditions.

SYNTHESIS OF SOME AMINO ACID ESTER LINKED DIOXATHIAPHOSPHOCIN/DIOXAPHOSPHOCIN DERIVATIVES

Novel 6/8-amido(methoxyglycinyl/alaninyl)dioxathiaphosphocins/dioxaphosphocins (4, 7, 10) have been synthesized from reactions of monochlorides (3,6,9) with glycine methyl ester or alanine methyl ester hydrochlorides (1a,b) at room temperature in dry tetrahydrofuran in the presence of triethylamine.

Enzymatic properties of sialic acid binding lectin from Rana catesbeiana modified with a water-soluble carbodiimide in the presence of various nucleophiles.

The anti-tumor activity of sialic acid binding lectin from Rana catesbeiana (cSBL) was increased by chemical modification with a water-soluble carbodiimide (EDC) in the presence of nucleophiles such as ethylenediamine and glycine methylester. Investigations on ribonuclease (RNase) activities of the modified cSBLs were conducted to elucidate the fundamental mechanisms underlying enhancement of the anti-tumor activity conferred by these modifications. The following three characteristics were observed with modification. (i) RNase activity of the modified cSBL was enhanced towards double stranded RNA and RNA-oligo dA hybrids. The activity increase was observed even under physiologic ionic strength conditions; (ii) RNase activity of the modified cSBL towards single stranded RNA and poly U decreased, while the activity towards poly C was unaffected; (iii) the base preference of the B2 base recognition site of modified cSBL decreased for guanine. On the contrary, the preference for cytosine and adenine increased. This result may explain why the RNase activity towards poly C was not affected by EDC-modification as mentioned above.

Effect of modification of the carboxyl groups of the sialic acid binding lectin from bullfrog (Rana catesbeiana) oocyte on anti-tumor activity.

The sialic acid binding lectin from bullfrog Rana catesbeiana oocyte (cSBL) is known to have anti-tumor activity. In order to investigate the relationship between the net charge of cSBL and its anti-tumor effect, cSBL was modified with a water-soluble carbodiimide (EDC) in the presence of three kinds of nucleophiles, taurine, glycine methylester and ethylenediamine. cSBL having four carboxyl groups was partially modified (ca. 2 residues). The anti-tumor activity of modified cSBLs was in the order of ethylenediamine-modified cSBL > glycine methylester-modified cSBL > taurine modified cSBL > or = native cSBL. The results suggested that anti-tumor activity seems to increase with the increase in positive net charge, possibly enhancing the interaction of cSBL with sialoglycoprotein on the surface of tumor cells. The ribonuclease activity of ethylenediamine-modified cSBL decreased with the progress of the reaction, but the number of internalized molecules in the tumor cell increased. Thus, for antitumor activity, a higher incorporation of cSBL with reasonable RNase activity seems to be more important than total RNase activity.

Synthesis of Some Novel Benzylidenehydantoins: Amino Acids Derivatives

5-Benzylidenehydantoin reacts with chlorosulfonic acid to give the corresponding p-sulfonyl chloride. Condensation of the latter with amino acids leads to sulfonylamino acid derivatives, which on coupling with glycine methyl ester hydrochloride in THF-Et3N using the dicyclohexylcarbodiimide method furnish the desired dipeptide methyl esters. The spectral data of the compounds are briefly discussed.

Formation and Stability of Organic Zwitterions in Aqueous Solution: Enolates of the Amino Acid Glycine and Its Derivatives

Second-order rate constants for carbon deprotonation of glycine zwitterion, N-protonated glycine methyl ester, betaine methyl ester, and betaine by deuterioxide ion in D2O have been determined by following deuterium exchange into these carbon acids in buffered solutions at 25 °C and I = 1.0 (KCl) by 1H NMR spectroscopy. The data were used to calculate the following carbon acidities for glycine zwitterion and its derivatives in aqueous solution: +H3NCH2CO2-, pKa = 28.9 ± 0.5; +H3NCH2CO2Me, pKa = 21.0 ± 1.0; +Me3NCH2CO2Me, pKa = 18.0 ± 1.0; +Me3NCH2CO2-, pKa = 27.3 ± 1.2. The rate constants for deprotonation of glycine methyl ester by Bronsted base catalysts are correlated by β = 0.92. Two important differences between structure−reactivity relationships for deprotonation of neutral α-carbonyl carbon acids and cationic esters are attributed to the presence of the positively charged ammonium substituent at the latter carbon acids: (1) The smaller negative deviation of log kDO from the Bronsted correlation f...

Effects of chemical modification of carboxyl groups in the hemolytic lectin CEL-III on its hemolytic and carbohydrate-binding activities.

Effects of chemical modification of carboxyl groups in the hemolytic lectin CEL-III on its activities were investigated. When carboxyl groups were modified with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and glycine methyl ester, hemolytic activity of CEL-III decreased as the EDC concentration increased, accompanied by reduction of oligomerization ability and hemagglutinating activity. However, binding ability of CEL-III for immobilized lactose was retained fairly well after modification, suggesting that one of two carbohydrate-binding sites might be responsible for such inactivation of CEL-III.

Carboxylate groups on the manganese-stabilizing protein are required for its efficient binding to photosystem II.

The effects of the modification of carboxylate groups on the manganese-stabilizing protein of photosystem II were investigated. Carboxylate groups (including possibly the C-terminus) on the manganese-stabilizing protein were modified with glycine methyl ester in a reaction facilitated by 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide. The manganese-stabilizing protein that was modified while associated with NaCl-washed photosystem II membranes contained 1-2 modified carboxylates, whereas the protein that was modified while free in solution contained 4 modified carboxylates. Both types of modified protein could reconstitute oxygen evolution at high manganese-stabilizing protein to photosystem II reaction center ratios. However, the protein that had been modified in solution exhibited a dramatically altered binding affinity for photosystem II. No such alteration in binding affinity was observed for the protein that had been modified while associated with the photosystem. Mapping of the sites of modification was carried out by trypsin and Staphylococcus V8 protease digestion of the modified proteins and analysis by matrix-assisted laser desorption/ionization mass spectrometry. These studies indicated that the domains (157)D-(168)D and (212)E-(247)Q (C-terminus) are labeled only when the manganese-stabilizing protein is modified in solution. Modified carboxylates in these domains are responsible for the altered binding affinity of this protein for the photosystem.

Novel Syntheses of 2-Butyl-5-chloro-3H-imidazole-4-carbaldehyde: A Key Intermediate for the Synthesis of the Angiotensin II Antagonist Losartan.

Reaction of glycine methyl ester (19) with imidate 18 under carefully optimized conditions allowed preparation of the rather unstable imidazolinone 11 in ca. 90% yield. Reaction of 11 with POCl(3)/DMF followed by aqueous workup gave aldehyde 2, a key intermediate for the synthesis of the angiotensin II antagonist Losartan, in ca. 55% yield. Structural identification of intermediates and byproducts formed during both the reaction to prepare 11 and the reaction of 11 with POCl(3)/DMF allowed development of several closely related syntheses of aldehyde 2.

Electrochemical anion recognition by redox-responsive unnatural amino acid derivatives; the X-ray crystal structure of N-ferrocenoyl glycine methyl ester, ( η5-C 5H 5)Fe( η5-C 5H 4)CONHCH 2COOMe

N-Ferrocenoyl glycine ester derivatives FcCONHCH 2COOR (Fc=( η 5-C 5H 5)Fe( η 5-C 5H 4); R=methyl ( 1), ethyl ( 2) and benzyl ( 3)) have been prepared by coupling ferrocene carboxylic acid to a series of glycine esters using 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBT) and Et 3N in CH 2Cl 2. The electrochemical anion sensing using a platinum microdisk working electrode of these N-ferrocenoyl glycine ester derivatives is reported. The crystal structure of 1 has been determined; principal dimensions are amide N(H)CO 1.229(3) Å, ester CO 1.183(3) Å with N–H⋯OC(amide) as the primary intermolecular hydrogen bond, N⋯O 2.804(3) Å.

Greatly Simplified Procedures for the Synthesis of alpha-Amino Acids by the Direct Alkylation of Pseudoephedrine Glycinamide Hydrate.

A modified procedure for the synthesis of highly enantiomerically enriched alpha-amino acids is described that involves the direct alkylation of pseudoephedrine glycinamide hydrate (1.H(2)O) followed by hydrolysis. The modified procedure was developed to overcome several inconvenient aspects of our earlier reported procedure. Advantages of the new method include (1) a greatly simplified one-step synthesis of the alkylation substrate (1.H(2)O) by the direct combination of glycine methyl ester hydrochloride with pseudoephedrine in the presence of lithium tert-butoxide, (2) the use of the weaker base lithium hexamethyldisilazide (LHMDS) in lieu of lithium diisopropylamide (LDA) for the enolization reaction, (3) a protocol for the direct alkylation of 1.H(2)O without the need for prior drying of the alkylation substrate, and (4) a one-step alkylation procedure that generates LHMDS and anhydrous lithium chloride simultaneously from the reaction of lithium metal with n-hexyl chloride in the presence of hexamethyldisilazane.