Methyl N-methyl Research Articles

Mass Spectrometry Rearrangement Ions and Metabolic Pathway-Based Discovery of Indole Derivatives during the Aging Process in Citrus reticulata 'Chachi'.

The rapid analysis and characterization of compounds using mass spectrometry (MS) may overlook trace compounds. Although targeted analysis methods can significantly improve detection sensitivity, it is hard to discover novel scaffold compounds in the trace. This study developed a strategy for discovering trace compounds in the aging process of traditional Chinese medicine based on MS fragmentation and known metabolic pathways. Specifically, we found that the characteristic component of C. reticulata 'Chachi', methyl N-methyl anthranilate (MMA), fragmented in electrospray ionization coupled with collision-induced dissociation (CID) to produce the rearrangement ion 3-hydroxyindole, which was proven to exist in trace amounts in C. reticulata 'Chachi' based on comparison with the reference substance using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Combining the known metabolic pathways of 3-hydroxyindole and the possible methylation reactions that may occur during aging, a total of 10 possible indole derivatives were untargeted predicted. These compounds were confirmed to originate from MMA using purchased or synthesized reference substances, all of which were detected in C. reticulata 'Chachi' through LC-MS/MS, achieving trace compound analysis from untargeted to targeted. These results may contribute to explaining the aging mechanism of C. reticulata 'Chachi', and the strategy of using the CID-induced special rearrangement ion-binding metabolic pathway has potential application value for discovering trace compounds.

GC-MS analysis of honeybee products derived from medicinal plants

BackgroundHoneybees provide a wealth of valuable natural products containing health-promoting bioactive compounds, including honey, bee bread, bee venom, bee pollen, propolis, and royal jelly. In the present study, we investigated the chemical composition of four honeybee products (bees, honey, royal jelly, and bee bread) derived from three medicinal plants (marjoram, trifolium, and citrus) using headspace GC-MS.ResultsGC-MS analysis coupled with the headspace method resulted in identification of 24 volatile compounds in marjoram honey, 14 volatile compounds in trifolium honey, and 25 volatile compounds in citrus honey, e.g., some of these compounds appeared in all three types of honey aroma, which are 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 2-furancarboxaldehyde, 5-(hydroxymethyl) and other unique compounds specific for each type where 23 compounds were from marjoram bees, 38 compounds from trifolium bees, and about 37 compounds were identified in citrus bees where 2,4-decadienal, (E, E) and methyl N-methyl anthranilate were common in all. Furthermore, the volatile compounds of all three types of royal jelly aroma were acetic acid, 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one, 8-nonen-2-one and furfural where one compound appeared in both marjoram and trifolium royal jelly that is 2-furancarboxaldehyde,5-(Hydroxymethyl) and the volatile compounds in marjoram and citrus are 2,3-butanediol and 5-methylfurfural also only one volatile compound appear in both trifolium and citrus royal jelly that is furfur alcohol, Finally, 3 compounds from marjoram bee bread, 30 volatile compounds from trifolium bee bread, and 3 volatile compounds in citrus bee bread were identified.ConclusionsA detailed metabolomic analysis of the four honey product groups revealed an intriguing chemical diversity, with each sample exhibiting its own chemical fingerprint.

Process intensification and optimization for efficient production of dimethyl carbonate through urea alcoholysis using low-cost anhydrous zinc acetate catalyst

Anhydrous zinc acetate was used as a low-cost catalyst for the urea alcoholysis to produce dimethyl carbonate (DMC). Important operating variables including reaction time, temperature and catalyst amount were optimized using response surface methodology. Optimization was assessed through two different approaches. In the first approach, only DMC yield was maximized. N-methyl methyl carbamate (NMMC, the unfavorable byproduct) yield was minimized along with maximizing DMC yield in the second approach. Sobol sensitivity analysis uncovered that reaction temperature and the binary interaction of reaction temperature/catalyst amount were the most influential parameters on DMC yield with 57.01% and 29.17% impacts, respectively. Moreover, temperature and reaction time with 61.13% and 19.74% impacts were the most effective variables on NMMC yield. The multi-objective optimization results were more suitable for application in continuous production of DMC due to avoiding NMMC production. A modified continuous process was also proposed for DMC production. The main advantage of the preposed process was immediate extraction out of DMC from the reaction zone. To investigate the possible reaction mechanism, the Binding Energies (BEs) of the reactants were assessed using Density-Functional-Theory. Results illustrated that the highest BE values belong to the interaction of zinc with the nitrogen of methyl carbamate (MC).

Synthesis of a Constitutional Isomer of Armeniaspirol A, Pseudoarmeniaspirol A, via Lewis Acid-Mediated Rearrangement.

The natural product armeniaspirol possesses a unique spirocyclic N,O-ketal in an α,β-dichloro-α,β-unsaturated lactam scaffold that has proved challenging to synthesize. Herein, we characterize the oxidative chlorination of pyrrole-2-carboxylate derivatives that rapidly generates this scaffold. The scope of this oxidation was extended to a series of esters and amides. Pyrrole-2-ketones could not be converted into the lactam due to an oxidative fragmentation. This result was unexpected since chloro-armeniaspirol has been synthesized via oxidative chlorination of a pyrrole-2-ketone. Examination of this successful oxidation showed that the desired scaffold was accessed due to intramolecular trapping from the neighboring free phenol, preventing fragmentation. Using the product of methyl N-methyl pyrrole-2-carboxylate oxidation 7b, we attempted to access the natural product armeniaspirol 2; however, an unanticipated Lewis acid-mediated rearrangement led to formation of a constitutional isomer, pseudoarmeniaspirol A 1. A small panel of pseudoarmeniaspirol analogues was synthesized and evaluated for antibiotic activity, inhibition of the targets of armeniaspirol, ClpXP and ClpYQ, and protonophore activity. While pseudoarmeniaspirol shows antibiotic activity, it does not target ClpXP or ClpYQ and has less protonophore activity than the natural product.

Effect of distillation methods on the leaf essential oil of some Citrus cultivars

ABSTRACT This study aimed to characterize the chemical composition of the leaf essential oil (EO) of mandarin and tangor trees obtained by steam distillation and hydrodistillation. Leaf samples were collected during the pruning period from seven citrus cultivars in a property located in Pareci Novo, Rio Grande do Sul state, South Brazil. The leaves underwent hydrodistillation and steam distillation, and the obtained EO was analyzed by GC-MS and GC-FID. In general, the Citrus deliciosa mandarins had higher EO yields than the ‘Ponkan’ and tangors in both methods. The Citrus deliciosa mandarin trees presented higher amounts of methyl N-methyl anthranilate and γ-terpinene. In the EO of ‘Ponkan’, ‘URSBRS Hada’ and ‘Murcott’, there was a predominance of linalool and terpinen-4-ol. The extraction method influenced the contents of the compounds mainly, while the genetic factors determined the variations in the composition of the essential oil of citrus leaves.

RESTRAIN HYPERCHOLESTEROLEMIA WITH ORANGE AND MANDARIN VOLATILE AND FOLDED OILS

ABSTRACT The findings of this study proved that orange peels contain more twice oil yield over mandarin peels (0.24% and 0.12%, respectively). Concentrated orange and mandarin peel essential oils were obtained by fractional distillation. The chemical constituents of original orange and mandarin oils (OO and MO) and their fivefold (5FOO and 5FMO) were fractionated and identified by GC/MS and GC. Limonene was the major monoterpene component in orange and mandarin oils, 89.65% and 65.57%, respectively, followed by myrcene (3.95%) and γ-terpinene (23.07%) in orange and mandarin oils, respectively. Octanal (1.47%) and linalool (1.5%) were the abundant oxygenated components in orange and mandarin oils, respectively. The decrement percentages of limonene were 18.58 and19.25% in five fold orange and mandarin oils, respectively. The major oxygenated component in 5FOO was the alcoholic β- Cis-terpeneol (4.27%). The main esters of mandarin oil, methyl N-methyl anthranilate and geranyl acetate were increased to 0.45% and 1.05%, respectively in 5FMO. In general, total oxygenated compounds percentages increased by 6.9 and7.3 times after folding of orange and mandarin oils, respectively. The above mentioned oils, pure limonene and synthetic antioxidant (BHT) were orally administrated for hypercholesterolemic rats for four weeks. No significant differences were recorded among groups of rats administrated with all different tested oils in body weight gain (%) or feed intake (g) (p≤ 0.05). In general, all rat groups administrated with orange and mandarin oils and their concentrates, showed improvement in HDL levels nearly to normal level compared to the negative control. Thus, the decrement of serum cholesterol level among cholesterol-fed groups did not correlate with the amount of limonene consumed by rats and may be related to other minor components associated with limonene and shared in the antioxidant effect. The efficiency of folded oils on hypocholesterolemic rats did not affect by decreasing limonene by deterpenation process.

Chemical constituents isolated from the fungus Monascus sp.

Further study of a 95% EtOH extract of red mold rice fermented with the yellow mutant of the fungus Monascus sp. led to the isolation of one new chroman derivative, namely monascuskaochroman (1), together with nine known compounds. The structure of the new compound was determined as 4-(1-hydroxy-1-methyl- ethyl)-chroman-4-carboxylic acid amide. The known compounds were identified as monascin (2), ankaflavin (3), (3R,6R,7E)-(+)-3-hydroxy-4,7-megstigmadien-9-one (4), vanillin (5), syringic acid (6), 3,4,5-trimethoxybenzoic acid (7), trans-methyl p-coumarate (8), ferulic acid (9), and methyl N-methyl anthranylate (10).This is the first report of a naturally occurring chroman skeleton isolated from Monascus species. Compounds 4–10 were isolated from this species for the first time. Their structures were elucidated by 1D and 2D NMR spectroscopy together with HR-ESI-MS analysis, and comparison of the spectroscopic data with those reported for structurally related compounds.

Quantum chemical calculations for understanding and predicting toxicity. II. The phosphorylation step in the inhibition of ache by organophosphorus anticholinesterases

The first step in the inhibition of acetylcholinesterase (AChE) by organophosphorus anticholinesterases is formation of the organophosphorous molecule-AChE complex. In the first paper of this series it was shown that the first step can be modeled well by the use of three-dimensional electrostatic molecular potential contour maps around the P compound. The second phosphorylation step of the mechanism by which organophosphorous anticholinesterases of the general formula inhibit AChE is related to the acidity of X and to the bond strength of the P—X bond. For a series of compounds, aryl N-methyl methyl phosphoramidates, in which the P—X bond is constant, this paper shows that the quantum chemically calculated P-O total overlap populations (TOPs) correlate the experimental log I50 for inhibition of AChE over four orders of magnitude with correlation coefficients of 0.96 [r2: TOP 0.9581; (TOP)1/2 0.9614].

Toward the control of Leptosphaeria maculans: Design, syntheses, biological activity, and metabolism of potential detoxification inhibitors of the crucifer phytoalexin brassinin

Brassinin ( 1), a crucial plant defense produced by crucifers, is detoxified by the phytopathogenic fungus Leptosphaeria maculans ( Phoma lingam) to indole-3-carboxaldehyde using a putative brassinin oxidase. Potential inhibitors of brassinin detoxification were designed by replacement of its dithiocarbamate group (toxophore) with carbamate, dithiocarbonate, urea, thiourea, sulfamide, sulfonamide, dithiocarbazate, amide, and ester functional groups. In addition, the indolyl moiety was substituted for naphthalenyl and phenyl. The syntheses and chemical characterization of these potential detoxification inhibitors, along with their antifungal and cytotoxic activity, as well as screening using cultures of L. maculans are reported. Overall, three types of interaction were observed in cultures of L. maculans co-incubated with the potential inhibitors and brassinin: (1) a decrease on the rate of brassinin detoxification due to the strong inhibitory activity of the compound on fungal growth, (2) a decrease on the rate of brassinin detoxification due to the inhibitory activity of the compound on the putative brassinin oxidase, and (3) a low to no detectable effect on the rate of brassinin detoxification. A noticeable decrease in the rate of brassinin detoxification was observed in the presence of N′-methylbrassinin, methyl N-methyl- N-(naphthalen-2-ylmethyl) dithiocarbamate, tryptophol dithiocarbonate, and methyl 3-phenyldithiocarbazate. Tryptophol dithiocarbonate appeared to be the best inhibitor among the designed compounds, representing the first inhibitor of brassinin detoxification and potentially the first selective protecting agent of oilseed crucifers against L. maculans infestation.

Production of Natural Methyl Anthranilate by Microbial N-Demethylation of N-Methyl Methyl Anthranilate by the Topsoil-Isolated Bacterium Bacillus megaterium

Bacillus megaterium, isolated in a screening process from topsoil, was used for N-demethylation of natural N-methyl methyl anthranilate to produce natural methyl anthranilate. Maximal productivity of 70 mg/L/day was achieved under laboratory-scale conditions without further optimization. No byproducts were observed. Thus, production of "natural" methyl anthranilate using B. megaterium is a significant improvement over comparable already existing procedures.

Synthesis of Coumarins, 4‐Hydroxycoumarins, and 4‐Hydroxyquinolinones by Tellurium‐Triggered Cyclizations.

Coumarins, 4-hydroxycoumarins, and 4-hydroxyquinolin-2(1H)-ones can be conveniently prepared by treatment of alpha-halocarboxylic acid esters of salicylaldehyde, o-hydroxyacetophenone, methyl salicylate, and methyl N-methyl- or N-phenylanthranilates with sodium or lithium telluride. Phenylketene formation competes with cyclization of the alpha-chlorophenylacetate ester of methyl salicylate as demonstrated by a trapping experiment with benzylamine. Elemental tellurium may be recovered and reused.

Synthesis of Coumarins, 4-Hydroxycoumarins, and 4-Hydroxyquinolinones by Tellurium-Triggered Cyclizations1

Coumarins, 4-hydroxycoumarins, and 4-hydroxyquinolin-2(1H)-ones can be conveniently prepared by treatment of alpha-halocarboxylic acid esters of salicylaldehyde, o-hydroxyacetophenone, methyl salicylate, and methyl N-methyl- or N-phenylanthranilates with sodium or lithium telluride. Phenylketene formation competes with cyclization of the alpha-chlorophenylacetate ester of methyl salicylate as demonstrated by a trapping experiment with benzylamine. Elemental tellurium may be recovered and reused.

Transformation of methyl N-methyl- N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetates into 4-methylamino-5-nitrosopyrimidines and 9-methylpurin-8-ones

N-Methyl- N-(6-substituted-5-nitro-4-pyrimidinyl)aminoacetic acid methyl esters under the treatment of sodium alkoxides, depending on the nature of substituents in 6 position of the pyrimidine ring, undergo ring closure and rearrangement to give 6-substituted-4-methylamino-5-nitrosopyrimidines or 9-methylpurin-8-ones.

Volatile Constituents of Calamondin Peel and Juice (Citrus madurensis Lour.) Cultivated in the Philippines

The volatile constituents of fresh calamondin (Citrus madurensis Lour.) cultivated in the Philippines were investigated by GC and GC/MS. As a result, 58 and 98 compounds were identified from the peel and juice volatile concentrates, respectively. The characteristic flavor components of calamondin were examined by GC-olfactometry. Limonene, cis-linalool oxide, linalool, α-terpineol, (E,E)-2,4-decadienal, and methyl N-methyl anthranilate had high flavor dilution factors. Additionally, the enantiomeric ratio of limonene, linalool, terpinen-4-ol and α-terpineol in calamondin were measured by chiral GC.

Aroma Profiling of Leaf, Flower, Peel and In Vitro Embryo Tissues of “Ciaculli Late” Mandarin

Volatile compounds released from leaf, flower and peel as well as from somatic (nucellar) embryo tissues of “Tardivo di Ciaculli” or “Ciaculli late” mandarin have been collected/ concentrated by headspace solid phase microextraction, HS-SPME, and analyzed by GC-MS. The tehnique allowed the rapid comparison of the volatiles from the various sources; in particular, 19 compounds were identified for the embryos, 16 for leaf and flower and 13 for peel. Limonene was the most abundant volatile component of the embryo and peel while γ-terpinene was the major compound among volatiles from leaf and flower. Relatively high amounts of methyl N-methyl anthranilate and β-caryophyllene were also found, with the excerption of peel, in all the samples. Myrcene was higher than methyl N-methyl anthranilate and β-caryophyllene in flower volatiles.

Italian Citrus Petitgrain Oils. Part II. Composition of Mandarin Petitgrain Oil

The chemical composition of Italian industrial mandarin petitgrain oil was examined using GC on two capillary columns and a fully automated “on-line” HPLC-GC/MS (ITD) system and a GC/MS (quadrupole) system. Methyl N-methyl anthranilate was found to be the main component representing about 50% of the whole oil. γ-Terpinene (23.9–28.5%) was the main monoterpene hydrocarbon, followed by limonene (7.2–12.6%) and p-cymene (3.0–5.2%). Alcohols were found to represent only about 1% of the oil, while aldehydes were present only as traces.

Synthesis of some novel imidate derivatives of thiophene and furan: Investigations of their metallation properties and some synthetic applications

Methyl N-methyl- and methyl N-(2,4,6-trimethyl)phenyl-2-carboximidates of thiophene and furan have been synthesized in excellent yields by the reaction of sodium methoxide in methanol with the corresponding N-methyl- and N-(2,4,6-trimethyl)phenyl-2-carboximidoyl chlorides, which in turn, were obtained from their respective secondary amides by refluxing in neat thionyl chloride. A thorough investigation into the directed lithiation properties of the these heteroaryl-2-imidates with various lithiating agents, solvents, and reaction conditions revealed almost exclusive C5-lithiation. This regioselectivity is in contrast to the C3-lithiation reported for the oxazolino functionality (a cyclic imidate). The synthetic utility of the C5-lithiated intermediate of methyl N-methyl-thiophene-2-carboximidate with various electrophiles is demonstrated. C3-Lithiation has been effected in the case of methyl N-methylthiophene-2-carboximidate when the C5-position is blocked with a removable trimethylsilyl group. Methyl thiophene-2-carboximidate, an N-unsubstituted imidate, was found to eliminate methoxide ion and undergo subsequent C5-lithiation to give 5-lithiothiophene-2-carbonitrile with LDA. n-Butyllithium gave rise predominantly to products resulting from nucleophilic addition to the nitrile group.

FT-IR spectroscopic studies of polyurethanes: Part 3. Quantum chemical studies of the carbamate group and the urethane C-O-C hydrogen bonding in polyurethanes

Ab initio quantum chemical computations were carried out on (a) methyl carbamate, (b) N-methyl methyl carbamate, and (c) the N-methyl methyl carbamate dimers: (i) to determine the optimized parameters, the relative strengths of cis versus trans conformations, and the dipole moment of the carbamate group; (ii) to determine the optimized bond parameters of the N-methyl methyl carbamate (a model for the urethane C-O-C group) and the relative energies of the cis and trans conformations; (iii) to determine the relative strengths of the C-O-C and CO H-bonds. The basis set used was the 3-21G set of the gaussian 80 program obtained from QCPE, Bloomington, IN. Variations in the strengths of these two H-bonds with the Nctdot;O distance (where O is either the carbonyl or the urethane alkoxy oxygen atom) were studied and found to be similar in behavior. The cis carbamate group was found to be energetically more stable than the trans one by 10.74 kcal mol −1. The strength of the urethane C-O-C H-bond was computed to be 5.95 kcal mol −1, which is quite significant compared to the value of 8.25 kcal mol −1 for the more accepted “carbonyl” H-bond. The urethane C-O-C H-bond is found to be directional, specific and non-negligible. Computed dipole moments are in very good agreement with experimental results. Work with two more basis sets has indicated that the results so obtained are not dependent on the choice of the basis set.

ChemInform Abstract: Ab initio Investigation of Hydrogen Bonding by Carbamates: Complexes Including N‐Methyl Methylcarbamate, N‐Phenyl Methylcarbamate, Dimethyl Ether and Methyl Acetate.

Abstract Hydrogen bonds of the type NH··O which occur in interactions between N-methyl methyl carbamate or N-phenyl methylearbamate and (i) a second carbamate, (ii) an ester, and (iii) an ether are studied by ab initio methods using a minimal MINI-1 basis set. Of the three, the ether forms the strongest complex with a carbamate. Replacement of the methyl group bonded to the proton-donating N of the carbamate by a phenyl group leads to a somewhat stronger H-bond in all cases. The electron density patterns are typical of rearrangements that normally accompany H-bond formation.

Ab initio investigation of hydrogen bonding by carbamates: Complexes including N-methyl methylcarbamate, N-phenyl methylcarbamate, dimethyl ether and methyl acetate

Hydrogen bonds of the type NH··O which occur in interactions between N-methyl methyl carbamate or N-phenyl methylearbamate and (i) a second carbamate, (ii) an ester, and (iii) an ether are studied by ab initio methods using a minimal MINI-1 basis set. Of the three, the ether forms the strongest complex with a carbamate. Replacement of the methyl group bonded to the proton-donating N of the carbamate by a phenyl group leads to a somewhat stronger H-bond in all cases. The electron density patterns are typical of rearrangements that normally accompany H-bond formation.