A New Condensation Reaction for the Synthesis of Carboxylic Esters from Nearly Equimolar Amounts of Carboxylic Acids and Alcohols Using 2-Methyl-6-nitrobenzoic Anhydride

Shiina, Isamu; Ibuka, Ryoutarou; Kubota, Mari

doi:10.1246/cl.2002.286

Cited by 180 publications

(70 citation statements)

References 13 publications

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“…In the present study, tertiary amine moieties were successfully introduced to MA by esterifi cation with 3-hydroxy-1-methylpiperidine. Thus, the reaction for the synthesis of carboxylic esters by Shiina et al ( 10 ) appears to be useful not only for the derivatization of alcohols ( 13 ) but also for that of carboxylic acids. This derivative, DMP-MA, exhibited [M+H] + as the base peak by P-ESI-MS and the detection limit by SRM was more than 100 times lower than that of underivatized MA by SRM with N-ESI mode.…”

Section: Comparison Of the Sensitivities Between P-esi And N-esi Methodsmentioning

confidence: 99%

“…The solution of internal standard in acetonitrile led to deproteinization of the sample and the liquid phase was collected and evaporated to dryness at 80°C under a nitrogen stream. Derivatization of MA into DMP-MA was performed according to the Shiina method for the synthesis of carboxylic esters ( 10 ) with some modifi cations. The reagent mixture for derivatization consisted of 2-methyl-6-nitrobenzoic anhydride (67 mg), 4-dimethylaminopyridine (20 mg), pyridine (900 l), and 3-hydroxy-1-methylpiperidine (100 l).…”

Section: Sample Preparationmentioning

confidence: 99%

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Highly sensitive quantification of serum malonate, a possible marker for de novo lipogenesis, by LC-ESI-MS/MS

Honda

Yamashita

Ikegami

et al. 2009

Journal of Lipid Research

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This article is available online at http://www.jlr.org Acetyl-CoA carboxylase (ACC) is the rate-controlling enzyme in the fatty acid biosynthetic pathway, and catalyzes the formation of malonyl-CoA from acetyl-CoA plus bicarbonate. Malonyl-CoA is not only substrate for fatty acid synthase (FAS) but is also a potent inhibitor of carnitine palmitoyl transferase 1 ( 1 ), the rate-limiting enzyme of fatty acid ␤ -oxidation. Therefore, malonyl-CoA is a key molecule that controls fatty acid metabolism in the body. In addition, recent studies have shown that the level of hypothalamic malonyl-CoA is dynamically regulated by fasting and feeding and that it alters subsequent feeding behavior ( 2 ).To determine ACC activity in tissues, an invasive tissue biopsy is necessary. However, whole body synthesis of fatty acid may be evaluated by the quantifi cation of serum malonyl-CoA metabolites. This concept originates from our previous studies, which showed that serum concentrations of the immediate products of the rate-controlling enzymes in cholesterol and bile acid biosynthetic pathways refl ected the activities of the rate-controlling enzymes and whole body cholesterol and bile acid biosynthesis ( 3 ). Furthermore, patients with malonyl-CoA decarboxylase (MCD) defi ciency, who must have increased tissue malonyl-CoA concentrations, are characterized by markedly elevated urinary malonic acid (MA), called "malonic aciduria" ( 4 ). This phenomenon suggests that malonyl-CoA is easily hydrolyzed into MA by an unidentifi ed tissue thioesterase(s). Therefore, we thought that serum MA concentrations might well refl ect total body FAS.Abstract We describe a new sensitive and specifi c method for the quantifi cation of serum malonate (malonic acid, MA), which could be a new biomarker for de novo lipogenesis (fatty acid synthesis). This method is based upon a stable isotope-dilution technique using LC-MS/MS. MA from 50 l of serum was derivatized into di-(1-methyl-3-piperidinyl)malonate (DMP-MA) and quantifi ed by LC-MS/MS using the positive electrospray ionization mode. The detection limit of the DMP-MA was approximately 4.8 fmol (500 fg) (signal-to-noise ratio = 10), which was more than 100 times more sensitive compared with that of MA by LC-MS/MS using the negative electrospray ionization mode. The relative standard deviations between sample preparations and measurements made using the present method were 4.4% and 3.2%, respectively, by one-way ANOVA. Recovery experiments were performed using 50 l aliquots of normal human serum spiked with 9.6 pmol (1 ng) to 28.8 pmol (3 ng) of MA and were validated by orthogonal regression analysis. The results showed that the estimated amount within a 95% confi dence limit was 14.1 ± 1.1 pmol, which was in complete agreement with the observed X 0 = 15.0 ± 0.6 pmol, with a mean recovery of 96.0%. This method provides reliable and reproducible results for the quantifi cation of MA in human serum. Abbreviations: ACC, acetyl-CoA carboxylase; DMP-MA, Di-(1-methyl-3-piperidinyl)malonate; FAS, fatty aci...

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Section: Comparison Of the Sensitivities Between P-esi And N-esi Methodsmentioning

confidence: 99%

Section: Sample Preparationmentioning

confidence: 99%

Highly sensitive quantification of serum malonate, a possible marker for de novo lipogenesis, by LC-ESI-MS/MS

Honda

Yamashita

Ikegami

et al. 2009

Journal of Lipid Research

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“…As shown in Figure 1, the fusaric acid moiety was incorporated into the steroid molecule via 3␤-hydroxy group (1a, 3a, 4a) or 17␤-hydroxy group (2a) by ester formation with mixed anhydride method using 2-methyl-6-nitrobenzoic anhydride [21] and 4-dimethylaminopyridine. Fusarate formation by this method underwent quantitatively under mild condition with reaction yield of Ͼ85% for 1c, 2c, 3c, and 4c in the levels of 1 ng and 1 g as was observed in the pocolinate derivatization [13,14].…”

Section: Resultsmentioning

confidence: 99%

Fusaric acid as a novel proton-affinitive derivatizing reagent for highly sensitive quantification of hydroxysteroids by LC-ESI-MS/MS

Yamashita

Yamazaki

Komatsu

et al. 2010

J. Am. Soc. Mass Spectrom.

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A highly sensitive derivatization method for liquid chromatography (LC)-electrospray ionization (ESI) tandem mass spectrometry of dehydroepiandrosterone (DHEA), testosterone (T), pregnenolone (P5), and 17␣-OH-pregnenolone (17-OHP5) was developed based on the use of fusaric acid as a reagent. DHEA, P5, and 17-OHP5 were rapidly and quantitatively converted to the 3-fusarate esters by treatment with fusaric acid and 2-methyl-6-nitrobenzoic anhydride. The positive ESI-mass spectra of the fusarate esters of each steroid were dominated by the appearance of [M ϩ H] ϩ as base peaks. The fusarate derivatization of these steroids showed 17.6-fold (DHEA), 11.9-fold (P5), 3.3-fold (17-OHP5), and 1.8-fold (T) higher sensitivity to those of the corresponding picolinate derivatives in LC-selected reaction monitoring. (J Am Soc Mass Spectrom 2010, 21, 249 -253) © 2010 American Society for Mass Spectrometry I n the recent development of analytical methodology for hydroxysteroids that were generally insensitive to liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), two types of derivatization designs have been proposed to provide high sensitivity to such kind of steroid molecules. The introduction of permanently charged moieties into steroid molecules was proven to be a promising method [1][2][3][4]. The use of 1-methylpyridinium for hydroxy group [2] and 2-hydrazino-1-methylpyridine for carbonyl group [4] as derivatizing reagents showed higher sensitivity in analyses of testosterone (T), 5␣-dihydrotestosterone (DHT), and dehydroepiandrosterone (DHEA) by LC-ESI-MS/MS. However, the application of these permanently charged derivatives to steroids possessing more than two hydroxy and/or carbonyl groups in one molecule seemed to be inconvenient and failed to obtain simple ESI-mass spectra with the appearance of protonated molecule ([M ϩ H] ϩ ) due to the formation of multiple ions of [M Ϫ H] -and [M] 2ϩ [4]. The introduction of high proton-affinitive moiety into steroid molecules was the alternative choice to obtain simple ESI mass spectra characterized by the formation of [M ϩ H] ϩ with high intensity [5][6][7][8]. The use of dimethylaminoaphthalene-sulfonate [5,6], pyridine-sulfonate [7], pyridine-dicarboxylate [8] derivatives for steroidal hydroxyl group, and hydroxime [9, 10] and 2-pyridine-hydrazone [11] derivatives for steroidal ketones have been investigated. However, the introduction of sulfonate moieties was limited to the phenolic hydroxy group of estrogens. Derivatization of T and DHT with pyridine-2,3-dicarboxylic anhydride resulted in the formation of the mixture consisted of two regio-isomers of half esters in their chromatograms [8]. Generation of syn-and ant-isomeric peaks might also be inevitable in the analyses of T and DHT using hydroxime and pyridine-hydrazone derivatizations [9,11].Recently, we have demonstrated that the introduction of picolinate moiety into hydroxysteroids provided some advantages to LC-ESI-MS/MS analyses of these compounds in a positive mode, involv...

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“…The observed ratio was similar to that of reported value in the literature. 23 25,26) and 4-dimethylaminopyridine (DAP) followed by the solid-phase extraction resulted in the production of the ethyl ether-picolinyl derivative of aldosterone, 8, with a narrow HPLC peak (t R ϭ7.6 min). The Without the use of the solid-phase extraction, treatment of aldosterone with 35% HCl in EtOH or in MeOH followed by evaporation of the solvent under reduced pressure at 50°C resulted in the formation of compound 10 as a main product (t R ϭ3.9 min).…”

Section: Resultsmentioning

confidence: 99%

Preparation and Structural Elucidation of the Picolinyl Ester of Aldosterone for Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry

Yamashita

Tadokoro

Takahashi

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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A New Condensation Reaction for the Synthesis of Carboxylic Esters from Nearly Equimolar Amounts of Carboxylic Acids and Alcohols Using 2-Methyl-6-nitrobenzoic Anhydride

Abstract: Various carboxylic esters were obtained in excellent yields with high chemoselectivities from nearly equimolar amounts of carboxylic acids and alcohols using 2-methyl-6-nitrobenzoic anhydride with triethylamine in the presence of a catalytic amount of 4-(dimethylamino)pyridine.

Cited by 180 publications

References 13 publications

Highly sensitive quantification of serum malonate, a possible marker for de novo lipogenesis, by LC-ESI-MS/MS

Highly sensitive quantification of serum malonate, a possible marker for de novo lipogenesis, by LC-ESI-MS/MS

Fusaric acid as a novel proton-affinitive derivatizing reagent for highly sensitive quantification of hydroxysteroids by LC-ESI-MS/MS

Preparation and Structural Elucidation of the Picolinyl Ester of Aldosterone for Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry

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