4-Carboxy-4-hydroxy-2-aminoadipic acid and other acidic amino acids in Caylusea abyssinica

Two diastereoisomers of 4-carboxy-4-hydroxy-2-aminoadipic acid have been isolated from leaves and inflorescences of Caylusea abyssinica. Green parts of the plant also contain appreciable amounts of the two diastereoisomers of 4-hydroxy-4-methylglutamic acid, 3-(3-carboxyphenyl)alanine, (3-carboxyphenyl)glycine, 3-(3-carboxy-4-hydroxyphenyl)alanine, (3-carboxy-4-hydroxyphenyl)glycine and in low concentration 2-aminoadipic acid, saccharopine [(2S, 2′S)-N⁶-(2-glutaryl)lysine] and some γ-glutamyl peptides. The acidic amino acids were separated from other amino acids on an Ecteola ion exchange column with M pyridine as eluant.     

Transformation of 3-(3-carboxyphenyl)alanine in iris species An example of diversity in catabolism of secondary plant products

3-(3-Carboxyphenyl)-DL-[2-¹⁴C]alanine has been incorporated into four species of iris. In all species extensive metabolization takes place. In Iris × hollandica, in which both the alanine derivative and 3′-carboxyphenylglycine occur, the products identified are the glycine derivative, 3′-carboxyphenylacetate acid, 3′-carboxymandelic acid, and 3′-carboxyphenylglyoxylic acid. In I. sanguinea, in which the alanine and glycine derivatives also occur, the products identified are the glycine and acetic acid derivatives but the major product is 3-(3-hydroxymethylphenyl)alanine, a naturally occurring amino acid in this species. In I. tectorum, in which only the carboxy-substituted alanine derivative occurs, the products identified are the acetic acid and glyoxylic acid derivatives. In I. pallida, not containing any of the meta-substituted amino acids, the products identified are again the acetic acid and glyoxylic acid derivatives. The results have been further substantiated by incorporation of labelled 3′-carboxyphenylacetic acid and 3′-carboxymandelic acid into I. × hollandica and I. sanguinea.The results demonstrate three different metabolic patterns for the alanine derivative and confirm previous results on the pathway from the alanine to the glycine derivative. Furthermore, the results may be of significance for the elucidation of the catabolism of phenylalanine.     

Intermediates in the metabolism of m-carboxy-substituted aromatic amino acids in plants: Phenylpyruvic acids,mandelic acids,and phenylglyoxylic acids

Tracer experiments with ¹⁴C-labelled precursors in Iris × hollandica cv. Wedgwood, Roseda lutea L. and Reseda Odorata L. have demonstrated that 3-(3-carboxyphenyl)alanine and 3-(3-carboxy-4-hydroxyphenyl)alanine can be derived from the corresponding pyruvic acids, presumably by unspecific trans-aminations, and that (3-carboxyphenyl)glycine and (3-carboxy-4-hydroxy-phenyl)glycine can be derived from the corresponding phenylglyoxylic acids The glycine derivatives are derived from the alanine derivatives, and the corresponding mandelic acids are intermediates in these transformations. The corresponding phenylacetic acids are incorporated only slightly into the glycine derivatives, indicating that oxidation at the benzylic position in the C₆–C₃ compounds takes place early in the transformation. The corresponding cinnamics acids are not metabolized at all in the plants.     

Acidic amino acids in Reseda luteola

3-(3-Carboxyphenyl)alanine, (3-carboxyphenyl)glycine, 3-(3-carboxy-4-hydroxyphenyl)alanine and (3-carboxy-4-hydroxyphenyl)glycine occur in all parts of Reseda luteola. The concentrations of the two diastereoisomers of 2(S)-4-hydroxy-4-methylglutamic acid undergo seasonal variation, the highest concentrations occurring in the first part of the summer. Highest concentrations are found in the inflorescences. The two diastereoisomers of 2(S)-4-hydroxy-2-aminopimelic acid occur in appreciable amounts in all parts of the plant. They are easily transformed into two structurally different lactones, one of which is very unstable. The structures of these amino acids have been confirmed by synthesis. Green parts of R. luteola also contain substantial quantities of γ-glutamylglutamic acid and glutathione.     

l-3-(3′-Carboxy-4′-hydroxyphenyl)alanine (3-carboxytyrosine) in seeds of Neonotonia wightii (Glycine wightii) and its possible systematic significance

l-3-(3′-Carboxy-4′-hydroxyphenyl)alanine (3-carboxytyrosine) constitutes 3% of the seeds of Neonotonia wightii (Glycine wightii); it has also been detected in the seeds of 3 species belonging to 2 other genera of the Glycineae. The systematic significance of these findings is discussed.     

Incorporation of radioactive shikimic acid into N-(γ-Lglutamyl)-4-hydroxyaniline in Agaricus bisporus

Agaricus bisporus contains novel aromatic compounds. By incubation of the mushroom with [G-¹⁴ C] shikimic acid, the radioactivity was incorporated into tyrosine, phenylalanine and several unidentified metabolites. The most radioactive metabolite in the stipe and the cap was identified as $\text{N-(γ-}\text{L}\text{-glutamyl}\text{)-4-}\text{hyrroxyaniline}$. The radioactivity was proved to be localized in the 4-hydroxyaniline moiety of this compound.     

Shikimate Pathway Activity during Shoot Initiation in Tobacco Callus Cultures

The activity of the shikimic acid pathway during shoot initiation in tobacco (Nicotiana tabacum L. Wisconsin 38) callus was examined. Enhancement of the activities of 3-deoxy-d-arabino-heptulosonic acid 7-phosphate synthase, shikimate kinase, chorismate mutase, and anthranilate synthase was observed during culture of tobacco callus under shootforming conditions in comparison to tissue cultured under non-organforming conditions. Confirmation of these findings was obtained by examining the incorporation of d-[¹⁴C]glucose into quinic and shikimic acids and of [¹⁴C]shikimic acid into tyrosine, phenylalanine, and tryptophan.     

Incorporation of chorismic acid and 4-aminobenzoic acid into the 4-hydroxyaniline moiety of N-(γ-L-glutamyl)-4-hydroxyaniline in Agaricusbisporus

Agaricus bisporus contains the unique aniline derivative, $\text{N-(γ-}\text{L}\text{-}\text{glutamyl}\text{)-4-}\text{hydroxyaniline}$. ¹⁴C-labelled chorismic acid was quantitatively incorporated into the 4-hydroxyaniline moiety of this aniline derivative, whereas ¹⁴C-labelled prephenic acid and anthranilic acid were not incorporated into 4-hydroxyaniline. These observations indicate the branch point of the biosynthetic route of 4-hydroxyaniline in the shikimic acid pathway to be chorismic acid. Moreover, 4-aminobenzoic acid proved to be an effective precursor of 4-hydroxyaniline.     

Ligand design,synthesis and biological anti-HCV evaluations for genotypes 1b and 4a of certain 4-(3- & 4-[3-(3,5-dibromo-4-hydroxyphenyl)-propylamino]phenyl) butyric acids and 3-(3,5-dibromo-4-hydroxyphenyl)-propylamino-acetamidobenzoic acid esters

4-(4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylamino]phenyl)-4-oxo-butyric acid (V), 4-(3- & 4-[N-1-carboxy-3-(3,5-dibromo-4-hydroxyphenyl)-3-oxo-propylaminophenyl]-2-aryl-4-oxo-butyric acids (Xa–e) and 4-(2-alkyl-2-[N-3-(3,5-dibromo-4-hydroxyphenyl)-1-carboxy-3-oxo-propylamino]acetamido) benzoate esters (XVa–e) were designed, synthesized and biologically evaluated as anti-HCV for genotypes 1b and 4a. The design was based on their docking scores with HCV NS3/4A protease-binding site of the genotype 1b (1W3C), which is conserved in the genotype 4a structure. The docking scores predicted that most of these molecules have higher affinity to the HCV NS3/4A enzyme more than Indoline lead. These compounds were synthesized and evaluated for their cytopathic inhibitory activity against RAW HCV cell cultures of genotype 4a and also examined against Huh 5–2 HCV cell culture of genotype 1b, utilizing Luciferase and MTS assays. Compounds Xa and Xb have 95 and 80% of the activity of Ribavirin against genotype 4a and compounds XVa, XVb and XVd exerted high percentage inhibitory activity against genotype 1b equal 87.7, 84.3 and 82.8%, respectively, with low EC₅₀ doses.     

Biosynthesis of 3,4-dihydroxyphenylalanine in Vicia faba

Radioactive shikimic acid and l-tyrosine were shown to be efficient precursors of 3,4-dihydroxyphenylalanine (DOPA) in Vicia faba. [1-¹⁴C]Acetate and l[U-¹⁴C]phenylalanine were not incorporated into tyrosine or DOPA. Thus the synthesis of DOPA occurs via the shikimic acid pathway and tyrosine or a very closely related metabolise. Phenolase was present in etiolated plants in much larger quantities after a brief light exposure whereas DOPA concentration was relatively constant during all stages of plant growth. Partially purified phenolase did not catalyze the conversion of tyrosine to DOPA and does not appear to have a role in DOPA synthesis.     

Ascorbalamic acid: An ascorbigen-like plant constituent yielding in hot acid 3-(2-furoyl)alanine

Ascorbalamic acid (C₉H₁₃NO₈) was isolated from Brassica olerocea L. MS study of various methylated derivatives suggested a structure (Ia) derivable by CC coupling of C-3 of alanine with C-2 of ascorbic acid, followed by lactone → lactam rearrangement. Other derivatives provided supporting evidence, as did study of the reaction of L-3-chloroalanine with L-ascorbic acid in vitro. On treatment with hot 6 M HCl, ascorbalamic acid yielded L-aspartic acid and 3-(2-furoyl)alanine. For identification of the latter, DL-3-(2-furoyl)alanine and its N-2,4-dinitrophenyl and N-acetyl methyl ester derivatives were synthesized. Unlike ascorbigens, ascorbalamic acid is probably present in the living plant. It seemed to be present in all crucifers examined, but to have a capricious distribution in other orders. During permethylation, rearrangements of ester groups were observed, both with ascorbalamic acid and with pyrrolidonecarboxylic acid as a model.     

l-3-(3-carboxyfuran-4-yl)alanine,a new amino acid from the mushroom Phyllotopsis nidulans

A new amino acid has been discovered in uncombined form in extracts of the fruiting bodies of the mushroom, Phyllotopsis nidulans. Chemical and spectroscopic data support formulation of the structure as l-3-(3-carboxyfuran-4-yl)alanine.     

Synthesis of (S)-3-(1-hydroxy-p-carboran-12-yl)alanine, a novel hydrophobic tyrosine-mimetic for peptides

A new, p -carborane containing analog of tyrosine, 3-[1-hydroxy-1,12-dicarba-closo-dodecaboran (12)-12-yl]alanine, was prepared from protected 3-[1-hydroxy-1,12-dicarba-closo-dodecaboran (12)-12-yl]propionic acid in five steps using Oppolzer's sultam methodology for asymmetric hydroxyamination as the key step. The tyrosine mimetic can function as a hydrophobic surrogate for tyrosine residues in insect and mammalian neuropeptides to enhance the lipophilicity, and therefore, the cuticle and/or tissue permeability properties of mimetic analogs. As an amino acid, insertion of the mimic is not limited to the N-terminus but can replace a tyrosine residue at any position within a peptide sequence.     

Biosynthesis of naphthoqinones and anthraquinones in streptocarpus dunnii cell cultures

Administration of ^p13C- and ^p2H-labelled precursors to Streptocarpus dunnii cell cultures demonstrated that the naphthoquinones formed through aunique prenylation mode are biosynthesized via 4-(2'-carboxyphenyl)-4-oxobutanoic acid, 1,4-dihydroxy-2-naphthoic acid, lawsone and lawsone 2-prenyl ether, and that the anthraquinones are biosynthesized through prenylation of 2-carboxy-4-oxo-1-tetralone at the carboxy-bearing carbon atom to form 2-carboxy-2-prenyl-4-oxo-1-tetralone,or through ipso attack of the prenyl group on the corresponding carbon atom of 1,4-dihydroxy-2-naphthoic acid.     

3′-Hydroxypsilotin,a minor phenolic glycoside from Psilotum nudum

A new non-flavonoid glycoside, 3′-hydroxypsilotin {6-[4′-(β-D-glucopyranosyloxy)-3′-hydroxyphenyl]-5,6-dihydro-2-oxo-2H-pyran}, was isolated from Psilotum nudum by droplet counter current chromatography and preparative HPLC. The structure was established by spectroscopic analysis including ¹H and ¹³C NMR and high resolution mass spectrometry.     

Fungal metabolic model for tyrosinemia type 3: molecular characterization of a gene encoding a 4-hydroxy-phenyl pyruvate dioxygenase from Aspergillus nidulans

Mutations in the human HPD gene (encoding 4-hydroxyphenylpyruvic acid dioxygenase) cause hereditary tyrosinemia type 3 (HT3). We deleted the Aspergillus nidulans homologue (hpdA). We showed that the mutant strain is not able to grow in the presence of phenylalanine and that it accumulates increased concentrations of tyrosine and 4-hydroxyphenylpyruvic acid, mimicking the human HT3 phenotype.     

Characterization of a meta-Fluorotyrosine-Tolerant Cell Culture of Eschscholtzia californica Cham

A cell line of Eschscholtzia californica selected for meta-fluorotyrosine (MFT) tolerance was found to have 10-fold increased levels of phenylalanine and tyrosine compared to the parent line, while most other amino acids were only increased 2-fold. Tracer experiments with shikimic acid in the presence of MFT showed that the biosynthesis of the aromatic amino acids was not impaired in the tolerant line. Feeding experiments with phenylalanine, tyrosine, or shikimic acid also revealed a reduced turnover of the pools of the aromatic amino acids in the variant. Thus undisturbed de novo biosynthesis of the aromatic amino acids and dilution of toxic effects of MFT by the enlarged pool sizes seemed to be the main reason for the acquired tolerance. Despite the enlarged availability of the precursor tyrosine, formation of the benzophenanthridine alkaloids was enhanced neither in the growth nor in the production medium.     

Caldensinic acid,a prenylated benzoic acid from Piper caldense

The CH₂Cl₂ and MeOH extracts from leaves of Piper caldense were subjected to chromatographic separation procedures to afford the new prenylated benzoic acid, caldensinic acid (3-[(2′E,6′E,10′E)-11′-carboxy-3′,7′,15′-trimethylhexadeca-2′,6′,10′,14′-tetraenyl]-4,5-dihydroxybenzoic acid) whose structure was determined by spectral analysis, mainly NMR (¹H, ¹³C, HSQC, HMBC) and ESI-MS. The natural compound and derivatives displayed antifungal activity against the phytopathogenic fungi Cladosporium cladosporioides and C. sphaerospermum by direct bioautography.     

Structure-Plant Phytotoxic Activity Relationship of 7,7′-epoxylignanes, (+)- and (−)-verrucosin: Simplification on the aromatic ring substituents

The synthesized 7-aryl derivatives of (7R,7′S,8S,8′S)-(+)-verrucosin were applied to growth inhibitory activity test against ryegrass at 1 mM. 7-(3-Ethoxy-4-hydroxyphenyl) derivative 12 and 7-(2-hydroxyphenyl) derivative 4 showed comparable activity to those of (+)-verrucosin against the root (−95%) and the shoot (−60%), respectively. The growth inhibitory activity test against lettuce using synthesized 7-aryl derivatives of (7S,7′R,8R,8′R)-(−)-verrucosin at 1 mM showed that the activities of 7-(3-hydroxyphenyl) derivative 20 and 7-(3-ethoxy-4-hydroxyphenyl) derivative 28 are similar to that of (−)-verrucosin against the root (−95%). Against the shoot, 7-(3-hydroxyphenyl) derivative 20 showed higher activity (−80%) than that of (−)-verrucosin (−60%). As the next step, (7S,7′R,8R,8′R)-7-(3-hydroxyphenyl)-7′-aryl-(−)-verrucosin derivatives, in which the most effective 3-hydroxyphenyl group is employed as 7-aromatic ring, were synthesized for the assay against lettuce. In this experiment, 7′-(2-hydroxyphenyl) derivative 37 and 7′-(3-hydroxyphenyl) derivative 38 showed similar activity to that of derivative 20. The effect of 7- and 7′-aryl structures of 7,7′-epoxylignanes on the plant growth inhibitory activity was clarified. The 7- and 7′-aryl structures were simplified to show comparable activity to or higher activity than that of (−)-verrucosin. The plant growth inhibitory activity of a nutmeg component, (+)-fragransin C_3b, was estimated as −80% inhibition at 1 mM against ryegrass roots.     

Synthesis and urease inhibitory potential of benzophenone sulfonamide hybrid in vitro and in silico

This study deals with the synthesis of benzophenone sulfonamides hybrids (1–31) and screening against urease enzyme in vitro. Studies showed that several synthetic compounds were found to have good urease enzyme inhibitory activity. Compounds 1 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-nitrobenzenesulfonohydrazide), 2 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-3′′-nitrobenzenesulfonohydrazide), 3 (N′-((4′-hydroxyphenyl)(phenyl)methylene)-4′′-methoxybenzenesulfonohydrazide), 4 (3′′,5′′-dichloro-2′′-hydroxy-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 6 (2′′,4′′-dichloro-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 8 (5-(dimethylamino)-N′-((4-hydroxyphenyl)(phenyl)methylene)naphthalene-1-sulfono hydrazide), 10 (2′′-chloro-N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide), 12 (N′-((4′-hydroxyphenyl)(phenyl)methylene)benzenesulfonohydrazide) have found to be potently active having an IC₅₀ value in the range of 3.90–17.99?µM. These compounds showed superior activity than standard acetohydroxamic acid (IC₅₀?=?29.20?±?1.01?µM). Moreover, in silico studies on most active compounds were also performed to understand the binding interaction of most active compounds with active sites of urease enzyme. Structures of all the synthetic compounds were elucidated by ¹H NMR, ¹³C NMR, EI-MS and FAB-MS spectroscopic techniques.