Β-hydroxypropionic Acid Research Articles

β-Hydroxy Esters as Malonic Semialdehyde Proelectrophiles in Enantioselective Butadiene-Mediated Crotylation: Total Synthesis of Octalactins A and B.

Tractable and commercially available esters (and amides) of β-hydroxypropionic acid serve as malonic semialdehyde proelectrophiles in enantioselective ruthenium-catalyzed hydrogen autotransfer crotylations mediated by butadiene. Through iterative asymmetric butadiene-mediated crotylations of ethyl 3-hydroxypropanoate, total syntheses of the polyketide natural products octalactin A and B were achieved in fewer steps than previously possible.

N‐alkylation of chitosan by β‐halopropionic acids in the presence of various acceptors

AbstractN‐carboxyethylation of chitosan by β‐halopropionic acids in the presence of various proton and halogen ion acceptors was investigated. It has been observed that carboxyethylation of chitosan in aqueous medium is accompanied by the by‐processes of hydrolysis and dehydrohalogenation of the β‐halopropionic acids yielding β‐hydroxypropionic acid, bis(2‐carboxyethyl) ether, and acrylic acid. Degree of carboxyethyl substitution (DS) of chitosan and the relative rates of the by‐processes varied significantly depending on the conditions used and nature of the proton or halogen ion acceptor. At carboxyethylation of chitosan with the alkaline β‐bromopropionates, the DS increased in the order Cs+ < Rb+ < K+ ∼ Na+ < Li+. For alkaline earth salts BrCH2CH2COOM0.5 (M = Be2+, Mg2+, Ca2+, Sr2+, Ba2+), the highest DS was obtained with strontium and barium salts, which could be subsequently removed from the reaction mixture by precipitation as sulfates. Among the organic bases applied (tetrabutylammonium hydroxide, triethylamine, trimethylamine, pyridine, 4‐N,N‐dimethylaminopyridine, 2,6‐lutidine, and 1,5‐diazabicyclo[4.3.0] non‐5‐ene), the highest DS was obtained using a moderately strong base triethylamine. For the halogen acceptors (Pb2+, Ag+, Tl+), the stoichiometrically highest DS was achieved in a system comprising iodopropionic acid plus Tl+ and a comparable conversion rate was obtained using also a combination of chloropropionic acid and Ag+. A novel alternative preparative approach—gel‐state synthesis—was suggested that provides for the highest DS at the optimum reaction conditions. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2008

Unexpected Preference of the E. coli Translation System for the Ester Bond during Incorporation of Backbone-Elongated Substrates

There have been recent advances in the ribosomal synthesis of various molecules composed of nonnatural ribosomal substrates. However, the ribosome has strict limitations on substrates with elongated backbones. Here, we show an unexpected loophole in the E. coli translation system, based on a remarkable disparity in its selectivity for beta-amino/hydroxy acids. We challenged beta-hydroxypropionic acid (beta-HPA), which is less nucleophilic than beta-amino acids but free from protonation, to produce a new repertoire of ribosome-compatible but main-chain-elongated substrates. PAGE analysis and mass-coupled S-tag assays of amber suppression experiments using yeast suppressor tRNAPheCUA confirmed the actual incorporation of beta-HPA into proteins/oligopeptides. We investigated the side-chain effects of beta-HPA and found that the side chain at position alpha and R stereochemistry of the beta-substrate is preferred and even notably enhances the efficiency of incorporation as compared to the parent substrate. These results indicate that the E. coli translation machinery can utilize main-chain-elongated substrates if the pKa of the substrate is appropriately chosen.

High‐performance liquid chromatography/electrospray ionization tandem mass spectrometry of hydroxylated uroporphyrin and urochlorin derivatives formed by photochemical oxidation of uroporphyrinogen I

Hydroxylated uroporphyrin I and urochlorin I derivatives formed by photochemical oxidation of uroporphyrinogen I were separated by high-performance liquid chromatography and fully characterized by electrospray ionization tandem mass spectrometry. The porphyrins and chlorins were identified by analysis of their product ion spectra with each hydroxylated derivative giving a characteristic collision-induced dissociation fragmentation pattern. The porphyrins and chlorins characterized were meso-hydroxyuroporphyrin I, alpha-hydroxypropionic acid uroporphyrin I, beta-hydroxypropionic acid uroporphyrin I, hydroxyacetic acid uroporphyrin I, trans-7-hydroxy-8-spirolactoneurochlorin I, cis-7-hydroxy-8-spirolactoneurochlorin I and trans- and cis-7,8-dihydroxyurochlorins I.

Mannopeptimycins, novel antibacterial glycopeptides from Streptomyces hygroscopicus, LL-AC98.

A series of novel antibiotics with activity against methicillin-resistant staphylococci and vancomycin-resistant enterococci has been purified, and their structures have been characterized using spectroscopic analyses and chemical conversions. These antibiotics, designated mannopeptimycins alpha-epsilon (1-5), are glycosylated cyclic hexapeptides containing two stereoisomers of an unprecedented amino acid, alpha-amino-beta-[4'-(2'-iminoimidazolidinyl)]-beta-hydroxypropionic acid (Aiha), as a distinguishing feature. The cyclic peptide core of these antibiotics is attached to a mannosyl monosaccharide moiety in 2 and to mannosyl monosaccharide and disaccharide moieties in 1, 3, 4, and 5. The presence and position of an isovaleryl group in the terminal mannose (Man-B) in 3-5 are critical for retaining antibacterial potency.

N-dealkylation of an N-cyclopropylamine by horseradish peroxidase. Fate of the cyclopropyl group.

Cyclopropylamines inactivate cytochrome P450 enzymes which catalyze their oxidative N-dealkylation. A key intermediate in both processes is postulated to be a highly reactive aminium cation radical formed by single electron transfer (SET) oxidation of the nitrogen center, but direct evidence for this has remained elusive. To address this deficiency and identify the fate of the cyclopropyl group lost upon N-dealkylation, we have investigated the oxidation of N-cyclopropyl-N-methylaniline (3) by horseradish peroxidase, a well-known SET enzyme. For comparison, similar studies were carried out in parallel with N-isopropyl-N-methylaniline (9) and N,N-dimethylaniline (8). Under standard peroxidatic conditions (HRP, H(2)O(2), air), HRP oxidizes 8 completely to N-methylaniline (4) plus formaldehyde within 15-30 min, whereas 9 is oxidized more slowly (<10% in 60 min) to produce only N-isopropylaniline (10) and formaldehyde (acetone and 4 are not formed). In contrast to results with 9, oxidation of 3 is complete in <60 min and affords 4 (20% yield) plus traces of aniline. By using [1'-(14)C]-3, [1'-(13)C]-3, and [2',3'-(13)C]-3 as substrates, radiochemical and NMR analyses of incubation mixtures revealed that the complete oxidation of 3 by HRP yields 4 (0.2 mol), beta-hydroxypropionic acid (17, 0.2 mol), and N-methylquinolinium (16, 0.8 mol). In buffer purged with pure O(2), the complete oxidation of 3 yields 4 (0.7 mol), 17 (0.7 mol), and 16 (0.3 mol), while under anaerobic conditions, 16 is formed quantitatively from 3. These results indicate that the aminium ion formed by SET oxidation of 3 undergoes cyclopropyl ring fragmentation exclusively to generate a distonic cation radical (14+*) which then partitions between unimolecular cyclization (leading, after further oxidation, to 16) and bimolecular reaction with dissolved oxygen (leading to 4 and 17 in a 1:1 ratio). Neither beta-hydroxypropionaldehyde, acrolein, nor cyclopropanone hydrate are formed as SET metabolites of 3. The synthetic and analytical methods developed in the course of these studies should facilitate the application of cyclopropylamine-containing probes to reactions catalyzed by cytochrome P450 enzymes.

Peroxylated and Hydroxylated Uroporphyrins: a Study of their Production In Vitro in Enzymic and Chemical Model Systems

In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin (URO) have been isolated from the urine of patients suffering from porphyria. We have now investigated the mechanism of production of these oxygenated derivatives of URO, using both enzymic and chemical model systems and also the effect of exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen was incubated with haemolysates, peaks with the same retention times as peroxyacetic acid URO, meso-hydroxy URO and β-hydroxypropionic acid URO were all detected. The first of these was formed in sufficient amounts to allow its characterization by mass spectrometry. Under these conditions, peroxyacetic acid derivatives of heptacarboxy- late and pentacarboxylate porphyrins could also be produced from the corresponding porphyrinogens, but no peroxylated product could be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains are present) or from the fully oxidized URO. Similar results were obtained on re-oxidation of URO'gen in the xanthine oxidase–xanthine system and in the presence of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetra-acetic acid) and here again no peroxylated product could be detected from either COPRO'gen or URO. Finally, formation of peroxyacetic acid URO could be demonstrated during photo-oxidation of URO'gen and this was followed by light-induced loss of both URO and its peroxylated derivative. It is concluded that the oxygenated derivatives arise from the action of reactive oxygen species on the porphyrinogens (rather than the porphyrins), with one of the acetic acid side chain serving as the preferential (or exclusive target) for peroxylation.

Peroxylated and Hydroxylated Uroporphyrins: A Study of their Production In Vitro in Enzymic and Chemical Model Systems

In previous work certain hydroxylated and peroxylated derivatives of uroporphyrin (URO) have been isolated from the urine of patients suffering from porphyria. We have now investigated the mechanism of production of these oxygenated derivatives of URO, using both enzymic and chemical model systems and also the effect of exposure to light during reoxidation of uroporphyrinogen (URO'gen). When URO'gen was incubated with haemolysates, peaks with the same retention times as peroxyacetic acid URO, meso-hydroxy URO and beta-hydroxypropionic acid URO were all detected. The first of these was formed in sufficient amounts to allow its characterization by mass spectrometry. Under these conditions, peroxyacetic acid derivatives of heptacarboxylate and pentacarboxylate porphyrins could also be produced from the corresponding porphyrinogens, but no peroxylated product could be obtained from coproporphyrinogen (COPRO'gen, where no acetic acid side chains are present) or from the fully oxidized URO. Similar results were obtained on re-oxidation of URO'gen in the xanthine oxidase-xanthine system and in the presence of hydrogen peroxide/Fe-EDTA (ethylenediamine-tetraacetic acid) and here again no peroxylated product could be detected from either COPRO'gen or URO. Finally, formation of peroxyacetic acid URO could be demonstrated during photo-oxidation of URO'gen and this was followed by light-induced loss of both URO and its peroxylated derivative. It is concluded that the oxygenated derivatives arise from the action of reactive oxygen species on the porphyrinogens (rather than the porphyrins), with one of the acetic acid side chain serving as the preferential (or exclusive target) for peroxylation.

Degradation of acrylic acid by fungi from petrochemical activated sludge

Geotrichum sp. and Trichoderma sp. isolated from petrochemical effluent treatment plant activated sludge completely degraded 2 g acrylic acid/l as sole carbon source in 4 d. However, after neutralization with Ca(OH)2, concentration as high as 10 g/l was degraded in 6 d. During the degradation acetic acid and β-hydroxy propionic acid transiently accumulated.

Preparation and separation of hydroxy derivatives of uroporphyrinogen I by high-performance liquid chromatography with electrochemical detection

The preparation and high-performance liquid chromatography (HPLC) separation of meso-hydroxyuroporphyrinogen I, hydroxyacetic acid uroporphyrinogen I and β-hydroxypropionic acid uroporphyrinogen I is described. meso-Hydroxyuroporphyrin I, hydroxyacetic acid uroporphyrin I and β-hydroxypropionic acid uroporphyrin I were isolated from the urine of a patient with congenital erythropoietic porphyria. The porphyrins were reduced to the corresponding porphyrinogens with 3% (w/w) Na/Hg amalgam. The hydroxy porphyrinogens were separated on a Hypersil ODS column with 4% (v/v) acetonitrile in 1 M ammonium acetate buffer, pH 5.16, containing EDTA (0.27 m M) as the mobile phase, and detected electrochemically. Reduction of meso-hydroxyuroporphyrin I and hydroxyacetic acid uroporphyrin I, followed by HPLC analysis, showed that, in addition to the expected formation of meso-hydroxyuroporphyrinogen I and hydroxyacetic uroporphyrinogen I, respectively, uroporphyrinogen I was also produced. Reduction of β-hydroxypropionic acid uroporphyrin I, however, gave β-hydroxypropionic acid uroporphyrinogen I, acrylic acid uroporphyrinogen I and uroporphyrinogen I as the products. The peaks were identified by conversion into the porphyrin methyl esters and analysed by liquid secondary-ion mass spectrometry.

Isolation and characterization of new porphyrin metabolites in human porphyria cutanea tarda and in rats treated with hexachlorobenzene by HPTLC, HPLC and liquid secondary ion mass spectrometry.

Porphyrin metabolisms in human porphyria cutanea tarda (PCT) and in rats treated with hexachlorobenzene (HCB) have been studied in detail by high performance thin layer chromatography (HPTLC), high performance liquid chromatography (HPLC) and liquid secondary ion mass spectrometry (LSIMS). The analyses of porphyrin metabolites in the urine, faeces and liver biopsies of patients with PCT have shown that apart from uroporphyrin I and III and their expected decarboxylation intermediates and products, a complex mixture of many other porphyrins are present. The new porphyrins identified are: meso-hydroxyuroporphyrin III, beta-hydroxypropionic acid uroporphyrin III, hydroxyacetic acid uroporphyrin III, peroxyacetic acid uroporphyrin III, beta-hydroxyproionic acid heptacarboxylic acid porphyrin III, hydroxyacetic acid hepatocarboxylic porphyrin III and peroxyacetic acid pentacarboxylic porphyrin III.

?-hydroxypropionic acid production by Byssochlamys sp. grown on acrylic acid

A strain of Byssochlamys sp. produced β-hydroxypropionic acid when grown on media containing high concentrations of acrylic acid. The maximal production of β-hydroxypropionic acid was 4.8% when the initial culture medium contained 7% acrylic acid and 2% glucose, and the initial culture pH was adjusted to 7.0. β-Hydroxypropionic acid production from acrylic acid depended greatly on the pH of the culture medium. Calcium hydroxide was the best neutralizer.

Isolation and characterization of β‐hydroxypropionic acid‐ and hydroxyacetic acid‐uroporphyrin I in the urine of a patient with congenital erythropoietic porphyria by high performance liquid chromatography and liquid secondary ion mass spectrometry

beta-Hydroxypropionic acid- and hydroxyacetic acid-uroporphyrin I have been isolated from the urine of a patient with congenital erythropoietic porphyria by reversed phase high performance liquid chromatography. The compounds were characterized by their chemical behaviour and confirmed by liquid secondary ion mass spectrometry.

Production and isolation of reuterin, a growth inhibitor produced by Lactobacillus reuteri.

Lactobacillus reuteri is a prominent member of the Lactobacillus population in the gastrointestinal ecosystem of humans, poultry, swine, and other animals. Reuterin is a newly discovered, broad-spectrum antimicrobial substance produced by this species during fermentation of glycerol. In this report, we describe procedures for (i) producing reuterin in sufficient amounts to isolate from a fermentation mixture and (ii) isolating this substance by high-performance liquid chromatography. By using uniformly labeled [14C]glycerol, reuterin was identified as a product of glycerol fermentation associated with the production of beta-hydroxypropionic acid and trimethylene glycol.

Preparation of selectively isotopically labelled β-hydroxypropionic acid

Two efficient three-step one-pot procedures for the synthesis of any combination of selectively isotopically labelled β-hydroxypropionic acids from relatively inexpensive labelled sodium acetate and gaseous formaldehyde or carbon dioxide have been developed. [1-14C]-, [2-14C]-, [2-14C,2-3H]-, [2-13C]-, and [2-13C,2-2H2]-β-hydroxypropionates have been prepared. The question of selective reduction of the intermediate malonate half esters is discussed and the general procedures are described.

Coproporphyrinogen oxidase. II. Reaction mechanism and role of tyrosine residues on the activity.

Purified coproporphyrinogen oxidase catalyzed conversion of 2-beta-hydroxypropionic acid-4-propionic acid deuteroporphyrinogen IX, 2-propionic acid-4-beta-hydroxypropionic acid deuteroporphyrinogen IX, 2,4-bis (beta-hydroxypropionic acid) deuteroporphyrinogen IX, harderoporphyrinogen, and isoharderoporphyrinogen to protoporphyrinogen IX. This result suggests that the enzymatic conversion of propionate groups of coproporphyrinogen III to vinyl groups of protoporphyrinogen IX occurs stepwise starting from position 2 to 4 through beta-hydroxypropionate porphyrinogen as an intermediate. When coproporphyrinogen oxidase was treated with tetranitromethane, an initial modification of 1 tyrosine residue per molecule did not affect the enzyme activity, whereas modification of a second tyrosine residue resulted in a substantial inactivation of the enzyme. Conversion of 2,4-bis-(beta-hydroxypropionic acid) deuteroporphyrinogen XI into protoporphyrinogen IX was not affected by the tyrosine residue modification. Both modification and kinetic studies led to a conclusion that at least one tyrosine residue is involved in the active site of the enzyme, presumably participating in the initial reaction of the oxidation step of a propionate group to beta-hydroxypropionate.

Physico-chemical investigation on the complexes of indium(III) with Mercapto-, Hydroxy-, and Amino-substituted propionic acid

Potentiometric studies have been carried out on the metal complexes of indium(111) with β-mercaptopropionic, β-hydroxypropionic, and β-aminopropionic acid. The Calvin-Bjerrum pH-titration technique, as used by Irving and Rossotti, has been applied to determine the stepwise formation constants of the complexes. The logK values have been computed by alternative methods. Thermodynamic formation constants have been obtained by extrapolation of the values at various ionic concentrations. The values of overall changes in ΔG, ΔH, and ΔS accompanying complex formation have been evaluated at three different temperatures at an ionic strength of 0.lM (NaClO4). The stability constant of the indium(111) complex decreases as the subsituted group changes from SH to OH to NH2.

Ethylene production from beta-alanine by an enzyme powder.

In the investigation of a pathway for ethylene biosynthesis, intermediates arising from the metabolism of β-alanine-2-14C to ethylene by enzyme powders from wax-bean cotyledons were isolated and identified by paper and thin-layer chromatography. Quantitative determinations of the label have provided evidence for the conversion of β-alanine through malonic semialdehyde, β-hydroxypropionic acid, and acrylic acid to ethylene.

2,4-Bis-(β-hydroxypropionic Acid) Deuteroporphyrinogen IX, a Possible Intermediate between Coproporphyrinogen III and Protoporphyrin IX

Abstract 2,4-Bis-(β-hydroxypropionic acid) deuteroporphyrin IX tetramethyl ester was synthesized from trans-diacrylic deuteroporphyrin IX and crystallized. The melting point, absorption spectra in the visible region, molar extinction co-efficient, and nuclear magnetic resonance spectra are recorded. Dehydration of β-hydroxypropionic acid deuteroporphyrin IX in pyridine with p-toluenesulfonic acid resulted in a mixture of diacrylic acid deuteroporphyrin IX and monohydroxypropionic-monoacrylic deuteroporphyrin IX. No protoporphyrin IX was formed by this method. Chromic acid-pyridine oxidation of β-hydroxypropionic acid deuteroporphyrin IX gave a diacetyl deuteroporphyrin IX. Protoporphyrin IX was obtained in a yield of 45% from an acid-catalyzed reaction of β-hydroxypropionic acid deuteroporphyrinogen IX. Diacrylic deuteroporphyrin and monovinyl-monoacrylic deuteroporphyrin IX was obtained from β-hydroxypropionic acid deuteroporphyrinogen IX at 38° and neutral pH. Protoporphyrin IX was formed from β-hydroxypropionic acid deuteroporphyrinogen IX, but not from the oxidized form, in neutral anaerobic incubation with a mitochondrial enzyme. It is suggested that β-hydroxypropionic acid deuteroporphyrinogen IX, resulting from an oxygenase-type reaction, is dehydrated and decarboxylated to protoporphyrinogen IX.

The oxidation of glycols by acetic acid bacteria

1.1. Resting cells of 14 different strains of acetic acid bacteria oxidized 1,2-ethanediol, dl-1,2-propanediol, dl-1,3-butanediol, meso-2,3-butanediol and 1,4-butanediol.2.2. The oxidation of 22 different glycols was studied with resting cells of Gluconobacter oxydans (suboxydans).3.3. The end products of the oxidation of the following glycols with resting cells of either Gluconobacter oxydans (suboxydans) or Acetobacter aceti (liquefaciens) have been isolated and chemically identified: 1,2-ethanediol to glycollic acid, 1,3-propanediol to β-hydroxypropionic acid, 1,4-butanediol to succinic acid, 1,5-pentanediol to glutaric acid, 1,6-hexanediol to adipic acid, 1,7-heptanediol to pimelic acid and dl-1,3-butanediol to dl-β-hydroxybutyric acid. The oxidation of 1,4-butanediol and 1,5-pentanediol occurred in two steps.4.4. Acetobacter aceti (liquefaciens) was unable to grow in a medium with dl-1,3-butanediol as sole carbon source. This compound inhibited growth in culture media containing either ethanol or glycerol.5.5. All glycols which were oxidized by resting cells were also oxidized by the particulate fraction. d(−)-and l(+)-1,2-propanediol, d(−)-andl(+)-2,3-butanediol were oxidized to acetol, d(−)- and l(+)-acetylmethylcarbinol, respectively.6.6. A soluble NAD-linked primary alcohol dehydrogenase oxidized monohydric primary alcohols and ω-diols. dl-1,3-Butanediol was oxidized slowly at C-1.7.7. A soluble NAD-linked secondary alcohol dehydrogenase oxidized monohydric secondary alcohols and the secondary alcohol function of the following glycols: meso-2,3-butanediol, dl-2,3-butanediol, dl-1,2-propanediol, l(+)-1,2-propanediol, meso-3,4-hexanediol. and (−)-3,4-hexanediol. Meso-2,3-butanediol and meso-3,4-hexanediol were oxidized to l(+)-acetylcarbinol and (+)ethylpropionylcarbinol.8.8. Both soluble dehydrogenase were purified and separated by chromatography.