5-hydroxypipecolic Acid Research Articles

Hydroxypipecolic acids and hydroxyprolines as chemical characters in Aphanocalyx, Bikinia and Tetraberlinia (Leguminosae: Caesalpinioideae): support for the segregation of Monopetalanthus

The presence or absence of hydroxypipecolic acids and hydroxyprolines in leaves of members of the former genus Monopetalanthus Harms was generally found to support the recent segregation of species into Aphanocalyx Oliver, Bikinia Wieringa and Tetraberlinia (Harms) Hauman. The species transferred to Aphanocalyx were found to lack these non-protein amino acids, like species traditionally placed in that genus, while most of the species reclassified into the new genus Bikinia accumulated hydroxypipecolic acids and hydroxyprolines (the exceptions were B. aciculifera Wieringa , B. coriacea J. Morel ex Aubrév. and B. durandii F. Hallé & Normand). All seven known species of Tetraberlinia, including T. longiracemosa (A. Chev.) Wieringa, which was formerly placed in Monopetalanthus, also contained one or both types of compounds. In species of Bikinia and Tetraberlinia the hydroxypipecolic acids accumulated included trans-4-hydroxypipecolic acid, trans-4- trans-5-dihydroxypipecolic acid and cis-4- cis-5-dihydroxypipecolic acid. All except T. moreliana Aubrév. and T. korupensis Wieringa also accumulated N-methyl- trans-4-hydroxyproline and both of these species and T. bifoliolata (Harms) Hauman accumulated an epimer of N-methyl-4,5-dihydroxypipecolic acid. These chemical groupings of Tetraberlinia species are generally in accordance with those based on morphology.

Chemoenzymatic Synthesis of the Four Diastereoisomers of 4-Hydroxypipecolic Acid from N-Acetyl-(R,S)-allylglycine: Chiral Scaffolds for Drug Discovery

All four diastereoisomers of 4-hydroxypipecolic acid were prepared in a form conveniently protected for drug discovery applications with the use of industrially scaleable methodology. Resolution of the racemic starting material using proprietary acylases followed by an acyliminium ion cyclisation gave diastereomeric mixtures of 4-formyloxypipecolic acid, which were differentiated using an enzyme-catalysed hydrolysis. The products were separated by partition, and by following a sequence of straightforward chemical steps, the individual stereoisomers of the protected 4-hydroxypipecolates were crystallized to optical purity in 100 g quantities.

Synthesis of Phosphonic Analogues of 4-Hydroxyproline and 5-Hydroxypipecolic Acid

ABSTRACT Interest in non-natural amino acids is growing because of their potential biological activity. We describe in this paper, a synthesis of phosphonic analogues of 4-hydroxy proline and 5-hydroxy pipecolic acid.

Asymmetric Synthesis of the Four Stereoisomers of 4-Hydroxypipecolic Acid

Asymmetric Synthesis of the Four Stereoisomers of 4-Hydroxypipecolic Acid

Chemotaxonomic significance of hydroxylated pipecolic acids in Central American Inga (Fabaceae: Mimosoideae: Ingeae)

Hydroxylated pipecolic acid derivatives of 47 species of Inga were analyzed primarily from herbarium leaf samples supplemented by field collections. Inga species are noted for their morphological variability, which has resulted in considerable taxonomic confusion. Pipecolic acid chemistry appears to be a relatively stable character within species, and the large number of pipecolic acid derivatives translates to greater intraspecific diversity in chemical patterns (18 distinct hydroxypipecolic acid patterns) than previously found in related genera. This chemical diversity makes pipecolic acids particularly useful in solving taxonomic problems in this genus; problems such as identification of distinct species with convergent morphology and identification of mislabeled herbarium specimens. Chemistry provides data independent of morphology with which to assess recent changes in nomenclature (some of which are supported, others not) and may also be useful in the assessment of hybridization and in delimitation of proper species boundaries. At present our chemical knowledge is too fragmentary to allow strong statements regarding relationships above the species level, but there is a trend for taxa traditionally grouped on morphological criteria to share similar chemistries.

Analysis of hydroxypipecolic acids by gas chromatography-mass spectrometry

The development of a method is described for the analysis of hydroxypipecolic acids in crudely purified plant extracts. All eight known naturally-occurring mono- and di-hydroxypipecolic acids could be resolved in a single analysis by gas chromatography-mass spectrometry (GC–MS) of their trimethylsilyl derivatives. The mass spectra and retention times of these derivatives are provided. The applicability of the method to chemotaxonomic studies using hydroxypipecolic acids is assessed by surveying the patterns of these compounds in herbarium leaf material of 11 species of Inga. © 1997 John Wiley & Sons, Ltd.

Preparation of enantiopure 4-oxygenated pipecolic acid derivatives

Two approaches to enantiopure 4-oxo- and 4-( R)-hydroxypipecolic acid derivatives from protected L-aspartic acid were developed. The first route exploits an intramolecular Michael addition on the stable enaminone 8. Hydrogenation and concomitant decarboxylation gave the 4-oxo derivative 11 which was reduced selectively to the 4-( R)-hydroxy derivative 12. The second route starts with a Michael addition followed by an intramolecular Dieckmann condensation to build the piperidine ring. The 4-oxo derivatives 11 and 19 are thus obtained in an expeditious manner on large scale without any chromatographic purification. Both sequences proved to be highly stereoselective.

Analysis of hydroxypipecolic acids by gas chromatography–mass spectrometry

Analysis of hydroxypipecolic acids by gas chromatography–mass spectrometry

Pipecolic acid methyl esters as artefacts from the ion-exchange chromatography of Inga punctata foliar extracts

Methyl esters of hydroxypipecolic acids can be produced as artefacts when cation-exchange resin is used in the sample preparation of plant extracts for chromatographic analysis. Esterification occurs when extracts containing methanol are applied directly to the resin and subsequently washed through with methanolic solutions.

ChemInform Abstract: Synthesis of Enantiomerically Pure (2R,5S)‐ (XVII) and (2R,5R)‐5‐ Hydroxypipecolic Acid (XVIII) from Glycinate Schiff Bases (III).

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

4-Hydroxypipecolic Acid and Pipecolic Acid in Acacia Species: Their Determination by High-Performance Liquid Chromatography, Its Application to Leguminous Plants, and Configuration of 4-Hydroxypipecolic Acid

A new method for the determination of naturally occurring imino acids in plants was devised. This method comprises the formation of dinitrophenyl derivatives and their measurement by HPLC. The determination limits were 100 pmol for 4-hydroxypipecolic acid (HPA) and proline (Pro) and 10 pmol for pipecolic acid (Pip). The recoveries of HPA, Pro, and Pip from leaf homogenate of an Acacia species were 95.9 ± 2.8, 100.5 ± 1.7, and 101.1 ± 2.3%, respectively. HPA was found in leaves, seeds, and roots of five kinds of Acacia but not in leaves of other members of the legume family. The HPA content of Acacia dealbata link leaves was much higher in winter than in summer. From X-ray analysis, HPA was found to be hydrated by two water molecules that are situated in a vacant channel formed by the molecular arrangement of HPA. HPA had no remarkable physiological or pharmaceutical activities. Keywords: 4-Hydroxypipecolic acid; pipecolic acid; Acacia species; leguminous plants; determination

GC-MS analysis of nonprotein amino acids in Gymnocladus dioicus as N(O,S)-isobutyloxycarbonyl silyl derivatives.

Two different derivatives of novel nonprotein amino acids in Gymnocladus dioicus seeds are prepared for gas chromatographic (GC) and mass spectrometric (MS) analysis. The interfering components in a water extract of the seeds are removed by picric acid treatment and multistep washing with organic solvents followed by N(O,S)-isobutyloxycarbonylation combined with solid-phase extraction. The resulting N(O,S)-isobutyloxycarbonyl (isoBOC) amino acids are then converted to either tert-butyldimethylsilyl (TBDMS) or trimethylsilyl (TMS) derivatives, which are analyzed by dual capillary column GC and GC-MS. The characteristic ions in the mass spectra of N(O,S)-isoBOC TBDMS and N(O,S)-isoBOC TMS derivatives enable confirmation of molecular weight and existence of functional groups containing active protons. Temperature programmed retention index sets measured on DB-5 and DB-17 capillary columns (J&W Scientific; Folsom, CA) are useful for distinguishing among structural isomers. gamma-Methylglutamic acid, diastereoisomers of 3-hydroxy-4-methylglutamic acid, cis and trans isomers of 5-hydroxypipecolic acid, and some free protein amino acids are identified in Gymnocladus dioicus seeds.

Constituents of Byrsonima crassifolia and their Spasmogenic Activity

In a biological and phytochemical study on the leaves of Byrsonima crassifolia, 22 compounds were isolated and identified from a MeOH extract. Among the isolates were six triterpenes (betulinaldehyde, betulin, betulinic acid, lupeol, oleanolic acid, and ursenaldehyde), two sterols (β-sitosterol and its glucoside), six flavonoids (catechin, epicatechin, guaijaverin, hyperin, quercetin and its 3-0-[6″-galloyl]galactoside), an aromatic ester (methyl gallate), four common amino acids (alanine, aspartic acid, proline, and valine), two non-protein amino acids (pipecolic acid and 5-hydroxypipecolic acid), and a novel sulfonoglycolipid. Biological evaluations showed that five of these compounds (betulin, betulinic acid, hyperin, quercetin, and ursenaldehyde) exhibited spasmogenic activity on isolated rat fundus, and three isolates (hyperin, pipecolic acid and 5-hydroxypipecolic acid) showed noncompetitive antagonism to serotonin (5-HT) on the same preparation.

Sulfate esters of hydroxy amino acids as stereospecific glutamate receptor agonists

Enantiomerically pure sulfate esters of the hydroxy amino acids homserine, hydroxyproline and 4-hydroxypipecolic acid were synthesized and tested on α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N- methyl- D-aspartate (NMDA) receptors present in the mice cortical wedge preparation and on NMDA receptors present in the myenteric plexus of the guinea pig with the aim of finding new possible ligands (either agonists) for excitory amino acid receptors. The linear and flexible compound S-homoserine sulfate caused a depolarization of both AMPA and NMDA receptors. In the cortex its agonist action had an EC 50 of 150 μM for NMDA and 300 μM for AMPA receptors and in the myenteric plexus its EC 50 was 600 μM. The stereoisomer R-homoserine sulfate did not depolarize the cortical wedges and failed to cause ileal contraction up to a concentration of 500 μM. Among the four possible stereoisomers of 4-hydroxyproline sulfate, which are rigid structures and may be regarded as cyclization forms of homoserine sulfate, t- S-hydroxyproline sulfate was a selective AMPA receptor agonist with an EC 50 of 70 μM in the cortex. The other three isomers were not active as agonists up to 500 μM and none of them had antagonist activity. Finally, t-4- rmhydroxy- S-pipecolic acid-4-sulfate, a superior homologue of t- S-hydroxyproline sulfate, was found to be one of the most potent and selective NMDA receptor agonists so far described with an EC 50 of 0.7 μM in the cortex and 250 μM in the myenteric plexus. The cis-stereoisomer was significantly less potent (EC 50 75 μM in the cortex and no activity up to 500 μM in the myenteric plexus). In conclusion, S-homoserine sulfate, t- S-hydroxyproline sulfate and t-4-hydroxy- S-pipecolic acid-4-sulfate are natural compounds able to interact agonists in a stereospecific and selective manner with ionotropic glutamate receptors.

Characterization of nitrogenous solutes in tissues and xylem sap of Leucaena leucocephala.

Amino acid profiles of leaf, stem, and root tissues from nodulated and nonnodulated Leucaena leucocephala (Lam.) de Wit plants were determined by gas chromatography-mass spectrometry. High concentrations of mimosine and several other potentially toxic nonprotein amino acids, including pipecolic acid and two isomers of hydroxypipecolic acid, were identified in the tissues. Five metabolites remain unidentified. Of the foliar free amino acid nitrogen, 57-66% was associated with the potentially toxic amino acids. Major constituents in the leaf tissues of nonnodulated plants were mimosine and hydroxypipecolic acid (isomer 1). Mimosine was recovered in both the neutral plus basic and acidic amino acid fractions. Major differences between amino acid profiles of nodulated and nonnodulated roots were the low percentages of asparagine + aspartate (3.6% of the total pool compared to 33% in nodulated plants) and pipecolic acid in nonnodulated roots (1% of the total compared to 12.5% in nodulated plants). A novel plant betaine (dihydroxypipecolic acid betaine) was identified by fast-atom-bombardment mass spectrometry in leaf tissues, albeit at relatively low concentrations (< 1 micro mol per gram fresh weight). Analyses of the xylem sap collected from nodulated plants confirmed that Leucaena is an asparagine transporter, as suggested by the high concentrations of asparagine and the low concentrations of ureides in its root nodules. Amino acid profiles of xylem sap from nonnodulated plants showed extremely low concentrations of asparagine + aspartate (0.12 micro mol ml(-1)), whereas asparagine + aspartate was the major constituent (4.38 micro mol ml(-1)) in the xylem sap of nodulated plants. Two nonprotein amino acids, pipecolic acid and hydroxypipecolic acid, were major constituents of the xylem sap of nodulated and nonnodulated plants, respectively. Three unidentified compounds detected in xylem sap samples from both nodulated and nonnodulated plants did not correspond with any of the peaks characterized from tissue samples.

Selective determination of secondary amino acids as their N-dimethylthiophosphoryl methyl ester derivatives by gas chromatography with flame photometric detection

A selective and sensitive method for the determination of secondary amino acids by gas chromatography (GC) was developed. After removal of primary amino acids by reaction with o-phthalidialdehyde and subsequent extraction with diethyl ether, secondary amino acids were converted into their N-dimethylthiophosphoryl methyl ester derivatives and determined by GC with flame photometric detection using a DB-5 capillary column. The derivatives were volatile enough and stable, giving single and symmetrical peaks. The detection limits for proline, pipecolic acid, thioproline, hydroxyproline and hydroxypipecolic acid were 0.1–0.7 pmol injected. By using this method, low-nanomole amounts of secondary amino acids could be accurately and precisely determined without any influence from primary amino acids and other amines.

Identification and quantification of 5-hydroxypipecolic acid and 4-hydroxyproline in mammalian brain and blood by selected ion monitoring

A method for the analysis of 5-hydroxypipecolic acid and 4-hydroxyproline in mammalian brain and blood is reported. The identification and quantification of the two hydroxyimino acids were accomplished with gas chromatography/mass spectrometry including a selected ion-monitoring technique following HPLC prepurification. The lower limit of detection for the method is 2 to 10 pmol. The amounts of 5-hydroxypipecolic acid and 4-hydroxyproline in blood were 20 to 30 pmol/ml and 3 to 6 nmol/ml, respectively. Their concentrations in the rabbit whole brain were determined to be 5 and 120 pmol/g, respectively.

Biosynthesis of pipecolic acid and 4-hydroxypipecolic acid

Pipecolic acid is formed from lysine, and 4-hydroxypipecolic acid is formed from pipecolic acid in the leaves of Acacia mellifera subsp. detinens.

Insecticidal imino acids in leaves of Calliandra

Six amino acid components of the free amino acid pool of leaves of Calliendra species were tested for insticidal activity against a polyphagous herbivore Spodoptera frugiperda. Pipecolic acid, trans- 5-hydroxypipecolic acid, acetylaminopipecolic acid, trans-cis- 4,5-dihydroxypipecolic acid, trans-trans- 4,5-dihydroxypipecolic acid and the protein imino acid proline were incorporated into artificial diets. Negative effects on growth, metamorphosis, and survival were observed at concentrations ranging from 0.1 to 5.0% of the total diet.

Identification par RMN13C dans les Feuilles de Xylia xylocarpa de l'Acide trans–5–Hydroxypipecolique, Nouvel Inhibiteur de L'Agrégation Plaquettaire par la Serotonine

Trans–5–hydroxypipecolic acid has been identified by NMR of 13C in the leaves of Xylia xylocarpa. This iminoacid is a powerful inhibitor of platelet aggregation induced by serotonin and thus, it is probably involved in the biological effects of the plant extracts.