piperidines and pipecolic-acid

N,N-dimethylpiperidinium (mepiquat) is a new process-induced compound formed from natural constituents during the cooking process. Mepiquat was first found in coffee and cereal products, but its formation mechanism in coffee is still unclear. In the current study, Arabica and Robusta coffee beans were roasted at different temperatures (215, 220, and 230 °C) to study the effect of roasting process on mepiquat formation. The highest mepiquat content, 1,020 µg/kg, was found in dark roast (230 °C) Indonesia Wahana, while 430 µg/kg of mepiquat was detected in medium roast (220 °C) Vietnam Robusta. At the same roasting temperature, higher level of mepiquat was observed in Arabica than in Robusta. In both species, substances related to mepiquat formation, including betaine, choline, trigonelline, lysine, carnitine, pipecolic acid (PipAc), pipecolic acid betaine (PipBet), were also detected. The lysine-based Maillard reaction and decarboxylation in Arabica and Robusta promoted mepiquat formation through the degradation of choline and trigonelline, and the formation of intermediate products. Results from both the model system and selected commercial beans showed that choline and trigonelline had a significant correlation (P < 0.01) with mepiquat formation in Arabica. PRACTICAL APPLICATION: Mepiquat is considered as a new process-induced compound resulting from typical roasting conditions, but its formation mechanism in coffee is still unclear. This work demonstrates the formation mechanism of mepiquat by many precursor substances contained in Arabica and Robusta. It is very important to figure out how mepiquat is ''naturally" present in daily diets, especially in those processed at high temperatures.

Topics: Alkaloids; Coffea; Coffee; Cooking; Hot Temperature; Indonesia; Maillard Reaction; Pipecolic Acids; Piperidines; Seeds

Carnitine is demonstrated as an effective methyl donor in the formation of the plant growth regulator N, N-dimethylpiperidinium (mepiquat), encompassing either N-methylation/decarboxylation of pipecolic acid, or Maillard pathways followed by transmethylation reactions. The formation of mepiquat and the intermediate compounds was monitored (180-300 °C, up to 180 min) using HPLC-MS/MS in different binary or ternary model systems composed of (i) lysine/fructose/carnitine, (ii) lysine/glucose/carnitine, or (iii) pipecolic acid (PipAc)/carnitine. The highest yield of mepiquat was 2.4% after 120 min incubation at 290 °C (PipAc/carnitine model system). The highest yield was recorded in fructose and glucose (Maillard) systems after 180 min at 230 °C. The full-scan mode was used to monitor the formation of the corresponding intermediates (piperidine and N-methylpiperidine, the demethylated intermediates of carnitine). The new pathways of mepiquat formation indicate that the occurrence of low levels of this thermally induced compound is potentially more widespread in some selected cooked foodstuffs. For the first time, mepiquat was detected in oven-cooked beef, reaching up to 82.5 μg/kg. These amounts are not expected to significantly contribute to the overall exposure via different foodstuffs, as reported in previous studies.

Topics: Carnitine; Chromatography, High Pressure Liquid; Hot Temperature; Maillard Reaction; Methylation; Pipecolic Acids; Piperidines; Plant Growth Regulators; Tandem Mass Spectrometry

Mepiquat (N,N-dimethylpiperidinium) is a plant growth regulator registered for use as its chloride salt in many countries on cereals and other crops. Recent model system studies have shown that natural chemicals present in crop plants, such as pipecolic acid and pipecolic acid betaine, may furnish mepiquat through different chemical pathways, when subjected to temperatures in the range of 200°C. In this study, we cooked raw vegetables that did not contain mepiquat to a palatable state using different traditional cooking methods, and detected mepiquat in 9 out of 11 oven-cooked vegetables, reaching up to 189μg/kg dry wt in oven-cooked broccoli. Commercial oven potato fries generated mepiquat during cooking, typically in the range of 20-60μg/kg. Only traces of mepiquat (<5μg/kg) were found in commercial potato crisps. This work demonstrates that mepiquat occurs at μg/kg levels in a variety of cooked vegetables, including potatoes.

Topics: Betaine; Cooking; Hot Temperature; Pipecolic Acids; Piperidines; Solanum tuberosum; Vegetables

A range of enantiopure polyhydroxylated piperidines, including (2R,3S,4R)-dihydroxypipecolic acid, (-)-3-epi-fagomine, (2S,3S,4R)-dihydroxyhomopipecolic acid, (2S,3R,4R)-dihydroxyhomopipecolic acid, and two trihydroxy-substituted homopipecolic acids, have been prepared using diastereoselective olefinic oxidations of a range of enantiopure tetrahydropyridines as the key step. The requisite substrates were readily prepared from tert-butyl sorbate using our diastereoselective hydroamination or aminohydroxylation protocols followed by ring-closing metathesis. After diastereoselective olefinic oxidation of the resultant enantiopure tetrahydropyridines and deprotection, enantiopure polyhydroxylated piperidines were isolated as single diastereoisomers (>99:1 dr) in good overall yield.

Topics: Imino Pyranoses; Molecular Structure; Oxidation-Reduction; Pipecolic Acids; Piperidines; Stereoisomerism

The preparation of optically pure quaternary piperidines, both fluorinated and non-fluorinated, has been achieved from a chiral imino lactone derived from (R)-phenylglycinol. In the case of the fluorinated derivatives, the addition of (trifluoromethyl)trimethylsilane (TMSCF(3)) followed by iodoamination and migration of the CF(3) group allowed access to four derivatives of α-(trifluoromethyl)pipecolic acid. A theoretical study of the CF(3)-group rearrangement has been carried out to help establish the reaction mechanism of this uncommon transformation. Moreover, a route to trifluoromethyl-substituted iminosugars was also developed through the diastereoselective dihydroxylation of suitable synthetic intermediates. Conversely, alkylation of the starting substrate and subsequent cross-metathesis and aza-Michael reactions led to α-alkyl derivatives of the target compounds.

Topics: Halogenation; Imino Sugars; Molecular Structure; Pipecolic Acids; Piperidines; Stereoisomerism

Enantiomeric syntheses of (-)-homopipecolic acid and (-)-pelletierine have been achieved by chiral resolution of tropanol followed by Baeyer-Villiger oxidation. The methodology provides a practical route for the synthesis of optically pure piperidines.

Topics: Models, Molecular; Molecular Structure; Pipecolic Acids; Piperidines; Stereoisomerism

A newly developed π-allylpalladium with a (-)-β-pinene framework and an isobutyl side chain catalyzed the enantioselective allylation of imines in good yields and enantioselectivities (20 examples, up to 98% ee). An efficient enantioselective synthesis of the (R)-α-propyl piperonylamine part of DMP 777, a human leukocyte elastase inhibitor and (R)-pipecolic acid have been achieved as a useful application of this methodology.

Topics: Bicyclic Monoterpenes; Bridged Bicyclo Compounds; Catalysis; Crystallography, X-Ray; Imines; Models, Molecular; Molecular Structure; Monoterpenes; Organometallic Compounds; Palladium; Pipecolic Acids; Piperidines; Stereoisomerism

The catalytic dynamic resolution (CDR) of rac-2-lithio-N-Boc-piperidine using chiral ligand 8 or its diastereomer 9 in the presence of TMEDA has led to the highly enantioselective syntheses of both enantiomers of 2-substituted piperidines using a wide range of electrophiles. The CDR has been applied to the synthesis of (R)- and (S)-pipecolic acid derivatives, (+)-beta-conhydrine, (S)-(+)-pelletierine, and (S)-(-)-ropivacaine and the formal synthesis of (-)-lasubine II and (+)-cermizine C.

Topics: Alkaloids; Amides; Catalysis; Heterocyclic Compounds, 2-Ring; Lithium; Molecular Conformation; Organometallic Compounds; Pipecolic Acids; Piperidines; Quinolizines; Ropivacaine; Stereoisomerism; Thermodynamics

An improved protocol for the construction of enantioenriched pyrrolidine, indoline, and piperidine rings using an organocatalyzed, intramolecular heteroatom Michael addition is described. Application to the enantioselective synthesis of homoproline, homopipecolic acid, and pelletierine has been accomplished.

Topics: Catalysis; Molecular Structure; Pipecolic Acids; Piperidines; Proline

An approach to 2,4,5-trisubstituted piperidines is reported, in which the key step is the Prins or carbonyl ene cyclisation of aldehydes of the type 1. Prins cyclisation catalysed by concentrated hydrochloric acid in CH(2)Cl(2) at -78 degrees C afforded good yields of two of the four possible diastereomeric piperidines, with the 4,5-cis product 7 predominating in a diastereomeric ratio of up to 94:6. The diastereoselectivity of the cyclisation decreased as the 2-substituent increased in size, becoming unselective for very bulky 2-substituents. In contrast, cyclisation catalysed by MeAlCl(2) in CH(2)Cl(2) or CHCl(3) at temperatures of between 20-60 degrees C, favoured the 4,5-trans diastereomer 8, in a diastereomeric ratio of up to 99:1. The low-temperature cyclisations catalysed by HCl proceed under kinetic control via a mechanism involving the development of significant carbocationic character, in which the 4,5-cis cation is more stable than the 4,5-trans cation as a result of overlap with the neighbouring oxygen. The cyclisations catalysed by MeAlCl(2) proceed under thermodynamic control, affording the product in which both the 4- and 5-substituents are equatorial.

Topics: Aldehydes; Amines; Amino Acids; Carbonic Acid; Catalysis; Cyclization; Hydrochloric Acid; Molecular Structure; Nitriles; Pipecolic Acids; Piperidines; Stereoisomerism

L-lysine catabolism in Pseudomonas putida KT2440 was generally thought to occur via the aminovalerate pathway. In this study we demonstrate the operation of the alternative aminoadipate pathway with the intermediates D-lysine, L-pipecolate, and aminoadipate. The simultaneous operation of both pathways for the use of L-lysine as the sole carbon and nitrogen source was confirmed genetically. Mutants with mutations in either pathway failed to use L-lysine as the sole carbon and nitrogen source, although they still used L-lysine as the nitrogen source, albeit at reduced growth rates. New genes were identified in both pathways, including the davB and davA genes that encode the enzymes involved in the oxidation of L-lysine to delta-aminovaleramide and the hydrolysis of the latter to delta-aminovalerate, respectively. The amaA, dkpA, and amaB genes, in contrast, encode proteins involved in the transformation of Delta1-piperidine-2-carboxylate into aminoadipate. Based on L-[U-13C, U-15N]lysine experiments, we quantified the relative use of pathways in the wild type and its isogenic mutants. The fate of 13C label of L-lysine indicates that in addition to the existing connection between the D- and L-lysine pathways at the early steps of the catabolism of L-lysine mediated by a lysine racemase, there is yet another interconnection at the lower end of the pathways in which aminoadipate is channeled to yield glutarate. This study establishes an unequivocal relationship between gene and pathway enzymes in the metabolism of L-lysine, which is of crucial importance for the successful colonization of the rhizosphere of plants by this microorganism.

Topics: 2-Aminoadipic Acid; Amino Acid Isomerases; Bacterial Proteins; Carbon; Carbon Radioisotopes; DNA Transposable Elements; Enzymes; Gas Chromatography-Mass Spectrometry; Genes, Bacterial; Glutarates; Lysine; Mutagenesis, Insertional; Mutation; Nitrogen; Pipecolic Acids; Piperidines; Pseudomonas putida; Valerates

Argatroban was synthesized in seven steps from 4-methylpiperidine. The condensation of (+/-)-trans-benzyl 4-methylpipecolic acid ester with N(alpha)-Boc-N(omega)-nitro-L-arginine led to two diastereomers that were separated. One of them is the precursor of argatroban.

Topics: Antithrombins; Arginine; Enzyme Inhibitors; Pipecolic Acids; Piperidines; Sensitivity and Specificity; Sulfonamides

Delta-1-Piperideine-6-carboxylate (P6C) dehydrogenase activity, which catalyses the conversion of P6C into alpha-aminoadipic acid, has been studied in the cephamycin C producer Streptomyces clavuligerus by both spectrophotometric and radiometric assays. The enzyme has been purified 124-fold to electrophoretic homogeneity with a 26% yield. The native protein is a monomer of 56.2 kDa that efficiently uses P6C (apparent Km 14 microM) and NAD+ (apparent Km 115 microM), but not NADP+ or other electron acceptors, as substrates. The enzyme activity was inhibited (by 66%) by its end product NADH at 0.1 mM concentration. It did not show activity towards pyrroline-5-carboxylate and was separated by Blue-Sepharose chromatography from pyrroline-5-carboxylate dehydrogenase, an enzyme involved in the catabolism of proline. P6C dehydrogenase reached maximal activity later than other early enzymes of the cephamycin pathway. The P6C dehydrogenase activity was decreased in ammonium (40 mM)-supplemented cultures, as was that of lysine 6 amino-transferase. P6C dehydrogenase activity was also found in other cephamycin C producers (Streptomyces cattleya and Nocardia lactamdurans) but no in actinomycetes that do no produce beta-lactams, suggesting that it is an enzyme specific for cephamycin biosynthesis, involved in the second stage of the two-step conversion of lysine to alpha-aminoadipic acid.

Topics: 2-Aminoadipic Acid; Bacterial Proteins; Cephamycins; Chromatography, Thin Layer; Electrophoresis, Polyacrylamide Gel; Enzyme Stability; Kinetics; L-Lysine 6-Transaminase; Lysine; Molecular Weight; NAD; Oxidoreductases Acting on CH-NH Group Donors; Picolinic Acids; Pipecolic Acids; Piperidines; Pyrroles; Quaternary Ammonium Compounds; Streptomyces; Substrate Specificity; Transaminases

Lysine and its metabolic intermediates were studied for their effect on pentylenetetrazol (PTZ)-induced seizures in mice. L-Lysine at dosages above 2 mmol/kg given i.p. significantly increased seizure protection and seizure latency (the time required to develop seizures after PTZ injection) with a peak effect dose at 10 mmol/kg. A pretreatment time of 15 min was required to significantly prolong seizure latency with a peak effect time of 45 min. D-Lysine at 10 mmol/kg i.p. afforded some seizure protection and significantly prolonged seizure latency but has a peak effect time of 15 min. When administered intracerebroventricularly, both L-lysine and piperidine at 0.1 mmol/kg prolonged seizure latency significantly, and increased seizure protection slightly. L-Pipecolic acid at the same dose given through the same route, however, shortened seizure latency significantly. L-alpha-Aminoadipic acid, on the other hand, had no significant effect. Lysine metabolites that prolonged seizure latency also increased seizure protection and decreased seizure death, and one that shortened seizure latency had the opposite effect. The anticonvulsant activity of lysine and its metabolites was explained on the basis of their connection with the GABAergic transmission.

Topics: 2-Aminoadipic Acid; Animals; Anticonvulsants; gamma-Aminobutyric Acid; Lysine; Male; Mice; Pentylenetetrazole; Pipecolic Acids; Piperidines; Seizures; Synaptic Transmission

Imino acid and related alicyclic amine concentrations in blood and urine of mammals including humans were concurrently determined by a selected ion monitoring technique. Nanomole levels of proline and pipecolic acid, and pyrrolidine and piperidine as well, were found in human urine. Proline levels but not pipecolic acid levels were higher in blood of humans than in urine. Pyrrolidine and piperidine levels in blood of humans were picomole levels and much lower than those in urine. Similar tendencies were also recognized when these 4 compounds were analyzed using animal blood and urine, although the levels were generally higher in animals than in humans. Significantly high concentrations of the imino acids and the amines were found also in animal semen.

Topics: Amines; Animals; Body Fluids; Female; Gas Chromatography-Mass Spectrometry; Humans; Imino Acids; Male; Pipecolic Acids; Piperidines; Proline; Pyrrolidines; Rabbits; Rats; Rats, Inbred Strains

Cadaverine and pipecolic acid metabolism was investigated in vitro in several organs of the mouse by measuring 14CO2 formation from labeled precursors. The liver showed the highest formation of 14CO2 from [1,5-14C]-cadaverine, whereas brain demonstrated a much lower formation. Anaerobiosis or inhibition of monoamineoxidase (MAO) activity significantly reduced 14CO2 formation in every organ, but inhibition of diamine oxidase (DAO) activity had no effect in brain and kidney. Piperidine was formed from cadaverine in vitro only in the large intestine and its content. This formation is probably of bacterial origin. Under a variety of experimental conditions we were unable to demonstrate any formation of piperidine in brain from cadaverine. Biosynthesis in vitro of [3H]-piperidine from D,L-[3H]-pipecolic acid was very low in brain and kidney. With the exception of brain and kidney, no other organs showed any formation of [3H]-piperidine. Neither MAO nor DAO inhibition influenced [3H]-piperidine formation in the large intestine with its content. Following 1 hr incubation at 37 degrees C under aerobic conditions, the levels of [14C]-pipecolic acid and [3H]-piperidine recovered from mouse brain homogenate did not indicate any significant degradation of these two substances. Our results suggest that under in vitro conditions, cadaverine is not a precursor of piperidine in brain, liver, heart, and kidney and that only very low levels of piperidine can be formed from pipecolic acid in brain. Outside the brain, formation of piperidine from pipecolic acid is detectable only in kidney and in the content of the large intestine. The latter is probably of bacterial origin. Our results do not support previous findings from other authors on an endogenous origin of piperidine in brain from cadaverine and pipecolic acid, and they suggest that a) cadaverine is not a precursor of piperidine in brain, b) the conversion of pipecolic acid into piperidine in the brain does not constitute a major metabolic pathway, and c) the main source of piperidine in the CNS may be of nonneural origin.

Topics: Animals; Brain; Cadaverine; Carbon Radioisotopes; Diamines; Intestine, Large; Kidney; Kinetics; Liver; Lysine; Mice; Myocardium; Organ Specificity; Pipecolic Acids; Piperidines

Topics: Amino Acids; Biochemical Phenomena; Carbon Isotopes; Carboxylic Acids; Lysine; Metabolism; Pipecolic Acids; Piperidines; Radiometry; Rats; Research

Topics: Animals; Carboxylic Acids; Lysine; Pipecolic Acids; Piperidines; Proteins; Rats

Topics: 2-Aminoadipic Acid; Amino Acids; Aspergillus; Aspergillus nidulans; Pipecolic Acids; Piperidines; Pyridines

Topics: 2-Aminoadipic Acid; Amino Acids; Carboxylic Acids; Pipecolic Acids; Piperidines; Pseudomonas

Topics: Amino Acids; Glutamates; Pipecolic Acids; Piperidines; Pseudomonas

Topics: 2-Aminoadipic Acid; Pipecolic Acids; Piperidines

Topics: Pipecolic Acids; Piperidines

Topics: Keto Acids; Liver; Lysine; Nucleotides; Organic Chemicals; Pipecolic Acids; Piperidines; Pyridines

Topics: Lysine; Pipecolic Acids; Piperidines

Topics: Pipecolic Acids; Piperidines; Proline

Topics: Biochemical Phenomena; Fabaceae; Lysine; Phaseolus; Pipecolic Acids; Piperidines