Β-hydroxy Amino Acids Research Articles

Reaction of coenzyme PQQ with amino acids. Oxidative decarboxylation, oxidative dealdolation (Cα–Cβfission) and oxazolopyrroloquinoline (OPQ) formation

The reactions of coenzyme PQQ (pyrroloquinolinequinone) and several amino acids have been investigated in vitro. PQQ catalyses the oxidative decarboxylation of α-amino acids to afford the corresponding aldehydes under aerobic conditions. During the catalytic cycles, PQQ is gradually converted into oxazolopyrroloquinoline (OPQ) derivatives to be deactivated. Product analyses indicate that the reaction proceeds via an ionic mechanism that involves a carbinolamine-type adduct as a key intermediate. From this intermediate, direct decarboxylation (major path) and dehydration followed by decarboxylation and hydrolysis or by intramolecular cyclization (minor paths) competitively occur to give the quinol, the aminophenol and the OPQ derivative, respectively. In the reactions with β-hydroxy amino acids, tyrosine and tryptophan, oxidative dealdolation (Cα–Cβ fission) proceeds effectively. The similar ionic mechanism that involves the carbinolamine-type intermediate is suggested by the product analyses under both aerobic and anaerobic conditions.

Stereospecific Synthesis ofN-(Diphenylmethylene)-α,β-didehydroamino Acid Methyl Esters from β-Hydroxy-α-amino Acids

N-(Diphenylmethylene)-α,β-didehydroamino acid methyl esters 2b-d are prepared with absolute geometric selectivity from inexpensive β-hydroxyamino acids through the intermediates N-(diphenylmethylene)- β-hydroxyamino acid methyl esters 1b-d. Besides, an easy conversion from E isomers to the corresponding Z isomers was performed, thus avoiding the use of the uncommon allo-β-hydroxyamino acids as starting materials.

Oxidative Cα–Cβfission (dealdolation) of β-hydroxy amino acids by coenzyme PQQ

Coenzyme PQQ is demonstrated to catalyse the oxidative Cα–Cβ fission (dealdolation) of β-hydroxy amino acids under very mild conditions.

Stereoselective synthesis of β-hydroxyamino acids by aldol reaction of α-isocyanocarboxylate with arene-chromium-tricarbonyl complexes.

High diastereoselectivity is obtained during the addition of ethyl isocyanoacetate 1 to chiral complexes 2 and 3 . The 2-oxazoline-4-carboxylic esters are intermediates for the synthesis of β-substituted serines in a stereoconservative process.

Synthesis of 2'-epi-distichonic acid A, an iron-chelating amino acid derivative.

2'-epi-Distichonic acid A (4b), an iron-chelating amino acid derivative was synthesized starting from L-vinylglycine epoxide (6b). Reaction of 6b with glycine ester 17 afforded a β-hydroxy amino acid derivative (18). Reductive coupling of 21 derived from 18 with L-malic-β-semialdehyde (25) gave 2'-epi-distichonic acid A (4b) after deprotection.

β-Lactam synthesis: Chemospecific sulfonation and cyclization of the β-hydroxyvaline nucleus

The intramolecular cyclization of “hydroxamate” 3 using Mitsunobu conditions was inefficient for the formation and isolation of the C-4 dimethyl monobactam 4 . However, chemospecific O-sulfonation of 1 and subsequent cyclization with base provides a useful method for β-lactam synthesis from a sterically hindered β-hydroxy amino acid. Competitive rearrangement of 3 also occurs during cyclization providing isomeric β-lactam 5 .

Ds- erythro-2-amino-4-ethoxy-3-hydroxybutanoic acid from the fruiting bodies of the edible mushroom, Lyophyllum ulmarium

A new β-hydroxy amino acid isolated from the fruiting bodies of Lyophyllum ulmarium was identified as D s,- erythro-2-amino-4-ethoxy-3-hydroxybutanoic acid by chemical degradation and spectroscopic analyses.

Anodic oxidation of amines. IX. Anodic oxidation process of .ALPHA.-amino acids in aqueous buffer of pH 10.

Anodic oxidation of α-amino acids with and without a β-hydroxy group was investigated by cyclic voltammetry and controlled potential electrolysis in aqueous carbonate buffer of pH 10. The first wave of the α-amino acids is developed at nearly the same potentials as those observed for the corresponding simple aliphatic amines, showing that a β-hydroxy group does not significantly decrease the first oxidation potential, in contrast to the case of β-alkanolamines. Decarboxylation accompanied by dealkylation is the main reaction process, and a small amount of C-C bond fission also occurs only in the case of the β-hydroxy amino acids.

Quantitation of the enantiomers of β-hydroxyamino acids by gas chromatographic resolution on an optically active packed column

Quantitation of the enantiomers of β-hydroxyamino acids by gas chromatographic resolution on an optically active packed column

β-Elimination of β-hydroxyamino acids with disuccinimido carbonate

Direct eliminations of β-hydroxyl groups and active ester formations from β-hydroxy amino acids under a one-step reaction with disuccinimido carbonate (DSC) are reported.

Serine transhydroxymethylase: Mechanism of aldolase activation by folate

Affinity chromatographic methods have been developed to purify beef liver serine transhydroxymethylase. This enzyme catalyzes both the transfer of aldehydic groups from β-hydroxy amino acids to tetrahydrofolate and the cleavage of β-hydroxy amino acids yielding the free aldehyde. Tetrahydrofolate, folate, and a quinazoline analog of isofolate were found to be activators of the β-phenylserine aldolase reaction catalyzed by serine transhydroxymethylase. Activation by folate was maximal at 20 μ m and higher concentrations diminished the activation. Evidence is presented suggesting that folate does not activate by providing an acceptor site for the aldehydic groups. Equilibrium binding studies showed that folate and tetrahydrofolate can bind the enzyme with essentially the same affinity. Double-reciprocal plots with β-phenylserine from steady-state kinetic experiments did not yield a 1 v 1 , intercept effect except at high folate concentrations. A mechanism is proposed in which folate binds readily to the enzymic active site, facilitating β-phenylserine binding. Folate is subsequently lost, at least partially, prior to product release and complete enzymic turnover.

The Structure-Taste Relationships of the Dipeptide Esters Composed of l-Aspartic Acid and β-Hydroxy Amino Acids

Abstract In order to evaluate the contribution of a hydroxyl group to the degree of sweetness of aspartyl dipeptides, we have synthesized a number of α-l-aspartyl dipeptides, such as the esters of α-l-aspartyl-l-hydroxynorleucine (16 and 17), -O-acyl-l-serine (18–21), -d-serine (22–28), -d-threonine (30–36), and -d-allothreonine (37–43); their sweetness potencies were compared with those of the corresponding dipeptides without a hydroxyl group. It has been found that a hydroxyl group makes a major contribution to the sweetness of the α-l-aspartyl dipeptide esters. Trie introduction of a hydroxyl group into the l-l peptides gave compounds with reduced potency. However, no such regularity was observed in the l–d peptides; the esters of α-l-aspartyl-d-serine (22–28) and -d-threonine (30–36) were sweeter than the corresponding esters of α-l-aspartyl-d-alanine and -d-α-amino-n-butyric acid respectively, while the esters of α-l-aspartyl-d-allothreonine (37–43) were less sweet than the corresponding esters of α-l-aspartyl-d-α-amino-n-butyric acid. The enzymatic resolution of N-acetyl-erythro- and -threo-β-hydroxy-Dl-norleucine is also described.

Studies on Roasting Changes of Proteins

Changes of casein and lysozyme during roasting at various times and temperatures 100 ~ 300°C), especially those in amino acid composition and formation of some nonvolatile degradation products, were investigated. Tryptophan, methionine, basic amino acids and β-hydroxy amino acids were easily decomposed as compared with acidic amino acids and other neutral amino acids in casein and Iysozyme. In hot water extract of roasted casein were detected some free amino acids, peptides, organic acids such as α-ketoglutaric, tartaric and malic acids, and indole. It is considered that free amino acids are produced mainly through ionic cleavage of peptide bond with the water bound within casein.

Studies on Roasting Changes of Proteins Part I

Changes of casein and lysozyme during roasting at various times and temperatures (100_??_300°C), especially those in amino acid composition and formation of some nonvolatile degradation products, were investigated. Tryptophan, methionine, basic amino acids and β-hydroxy amino acids were easily decomposed as compared with acidic amino acids and other neutral amino acids in casein and lysozyme. In hot water extract of roasted casein were detected some free amino acids, peptides, organic acids such as α-ketoglutarie, tartaric and malic acids, and indole. It is considered that free amino acids are produced mainly through ionic cleavage of peptide bond with the water bound within casein.

The biosynthesis of glycoproteins during the development of Dictyostelium discoideum. The transfer of D-mannose in vegetative and aggregated cells.

d-Mannose polysaccharide transferase is present in vegetative and aggregated cells of Dictyostelium discoideum. The enzyme together with the acceptor polymer for mannose are localized in subcellular fractions which were enriched from the microsomal and the 1500 ×g sediment fractions by sucrose density gradient centrifugation. The transfer of mannose into the acceptor depends on the development stage of the cells. During the aggregation period a steep rise in mannose transfer occurs. The fractions active in transferase consist of membraneous structures, ribosomal material being absent or at least extremely scarce. The enzymatic activity can be released partially by mild ultrasonic treatment, the acceptor function of the remaining particles cannot be destroyed by heat. The mannose transfer follows a two-step time course. During the initial phase of incubation a mannose containing intermediate is synthesized from GDP-Man. The linkage between the protein and the carbohydrate moieties of the acceptor consists predominantly of the O-glycosidic β-hydroxyamino acid type.

Prolysis of β-Hydroxy Amino Acids, Especially L-Serine

From the pyrolysis of l-serine, ten volatile compounds including several pyrazines were identified. Pyrazines were also found from the pyrolysis of l-threonine, but not from that of alanine and considered to be characteristic pyrolysis products of β-hydroxy amino acids. At the same time, diketopiperazines, amines and carbonyl compounds were also found in addition to those described above. Formation mechanism of pyrazine compounds was also discussed.

Synthesis of DL-threo- and DL-erythro-β-hydroxyisoleucine

DL-threo- and DL-erythro-β-Hydroxyisoleucine were prepared from cis- and trans-3-methylpent-2-enoic acids, respectively. The configuration of the erythro isomer was established from its synthesis by two independent routes. The diastereoisomers, and those of other β-hydroxy amino acids, can be distinguished by examination of their proton magnetic resonance spectra.

Caractérisation de la l- thréo-β-hydroxyleucine à partir de Deutzia gracilis

l- threo-β-Hydroxyleucine has been isolated from Deutzia gracilis by ion-exchange resin chromatography, and by preparative paper chromatography. The substance is reduced to leucine by hydroiodic acid and offers the characteristic reaction of β-hydroxyamino acids with periodic acid. Alkaline decomposition confirms the β position of the alcohol function. The natural substance and the dl- threo-β-hydroxyleucine are inseparable by paper chromatography, and the study of their nuclear-magnetic-resonance spectra brings supplementary arguments in favour of the threo form. The natural substance has the same infrared spectrum as synthetic threo-β-hydroxyleucine.

Studies on hydroxyamino acids. III. Effect on growth of Escherichia coli 9637

α-(Hydroxymethyl)serine, α-methylserine, α-ethylserine, β-hydroxyleucine, β-hydroxynorleucine, β-hydroxyaspartic acid, and β-( p-nitro)phenylserine were tested for biological activity in an Escherichia coli system. Of these, β-hydroxyaspartic acid and β-hydroxyleucine exhibited marked growth inhibitory activity. Certain naturally occurring amino acids, most of which were structurally similar to the inhibiting β-hydroxyamino acids, were shown to be capable of completely nullifying these inhibitory effects, while others, which were probably metabolically related to these amino acids, were capable of doing so to a lesser and varying extent. It appears that the inhibition is of the competitive type.

A new decomposition of serine and threonine by chloramine-T and periodate mixture

Recently, it was found that cyanogen chloride is formed by the oxidation of β-hydroxyamino acid with a mixture of Chloramine-T and periodate. Therefore serine and threonine were decomposed by the mixed oxidizer and oxidation products were identified by preparing derivatives and quantitative analysis. From the data obtained, it was concluded that serine and threonine are decomposed by the mixed oxidizer according to the following equation:RCH(OH)CH(NH2)COOH IO4-→Chloramine-T RCHO+ClCN+CO2