Synthesis Of Deuterium Research Articles

Synthesis of Deuterium or Tritium Labelled Glycin and Its Methyl Ester

Synthesis of Deuterium or Tritium Labelled Glycin and Its Methyl Ester

Synthesis of Deuterium- or Tritium-Labeled Norepinephrine and Evaluation of Its Biological Activity

A labeled norepinephrine analogue was prepared by bromination of norepinephrine with subsequent debromination with tritium or deuterium gas. The yield of tritiated norepinephrine was 10–20% with a molar radioactivity of 27 Ci/mmol. The biological activity of tritiated norepinephrine was evaluated by analyzing its specific capture by noradrenergic neutrons in thick sections of the brainstem and midbrain of Wistar rats, and in a suspension of cells of pheochromocytoma PC12 expressing the membrane transporter of norepinephrine. It is shown that tritium-labeled norepinephrine synthesized by the proposed method does not differ in biological activity from the natural norepinephrine.

Improved synthesis of the hypoxia probe 5-deutero-5-fluoro-5-deoxy-azomycin arabinoside (FAZA) as a model process for tritium radiolabeling

Tritium-labelled fluoroazomycin arabinoside, [3H]-FAZA, is a useful probe for the investigation of hypoxia, furthermore it is safer and easier to handle than the PET tracer [18F]-FAZA when used in cell based assays. The only known synthesis of deuterium- and tritium-labelled FAZA was re-investigated and optimized. Then, a new and improved synthesis of [2H]-FAZA was developed as a model process for tritium radiolabelling. This novel synthesis is expected to greatly facilitate access to [3H]-FAZA.

Synthesis of deuterium and C‐13‐labelled ethyl glycolate and their subsequent use in the synthesis of labelled analogues of the DNA adduct O6‐carboxymethyl‐2′‐deoxyguanosine

The adduct O6‐carboxymethyl‐2′‐deoxyguanosine (O6CMdG) is of importance as it has been previously linked to high red meat diet in humans, and as yet, a liquid chromatography‐mass spectrometry (LC‐MS) method has not been developed due to lack of appropriate standards. The synthesis of the deuterated and C‐13 analogues required the use of [2H2]‐ and [13C2]ethyl glycolate to label the carboxymethyl moiety of O6CMdG. [2H2]Ethyl glycolate was synthesised via acid hydrolysis of ethyl diazoacetate using deuterated solvents (59% yield), whilst [13C2]ethyl glycolate was synthesised from [13C2]glycine in a three‐step procedure (35% yield). The labelled ethyl glycolates were then used to synthesise [2H2]‐ and [13C2]O6CMdG for future use as internal standards in the LC‐MS analysis of biological samples. Copyright © 2011 John Wiley & Sons, Ltd.

Production of deuterium labelled (−)-epicatechin in a microreactor

Green tea catechins have been reported to have multiple health benefits. To understand their metabolic and toxicological interactions in the human body studies need to be undertaken using stable isotope labelled compounds, but they can be time consuming and expensive. Using microreactor technology labelling catechins could be produced more quickly and at a reduced cost. This research reports on a 2-step synthesis of deuterium labelled epicatechin developed using microreactor technology for the production.

Synthesis of Deuterium Labeled (±)‐2,5‐Dimethoxyamphetamine (DMA), (±)‐4‐Bromo‐2,5‐Dimethoxyamphetamine (DOB), and (±)‐4‐Methoxyamphetamine (PMA) as Internal Standards for Quantitative Analyses by GC‐MS

AbstractDMA, DOB and PMA are increasingly abused central nervous system stimulants with neurotoxic properties. In recent years, many controlled substance analogs (designer drugs) with a large variety of structures have reached the illegal market, making their identification difficult. Therefore, this work studies the synthesis of DOB‐d6, DMA‐d6 and PMA‐d3 as internal standards for use in gas chromatography‐mass spectrometry (GC‐MS) to identify controlled substances.

Synthesis of deuterium labelled 2-bromobenzylamine by directedortho-metalation chemistry

Directed ortho-metalation (DoM) strategy has been applied for the development of a short procedure for the regiospecific synthesis of [phenyl-2H4]-2-bromo-benzylamine 6 starting from commercially available [phenyl-2H5]-benzoyl chloride 1. A strong isotope effect was observed during the ortho-substitution. Copyright © 2005 John Wiley & Sons, Ltd.

Synthesis of deuterium- and tritium-labeled 25,26,26,26,27,27,27-heptafluorocholesterol

25,26,26,26,27,27,27-Heptafluorocholesterol (F7-cholesterol) is a novel analog of cholesterol with potential value in biological investigations. We have combined an isotope-labeling strategy described for 15-ketosterols with modifications in the original synthesis of F7-cholesterol to prepare analogs containing deuterium or tritium at the C-23 position. 1H, 2H, and 13C nuclear magnetic resonance spectra indicated high chemical purity of the deuterium-labeled analog and confirmed the presence of deuterium only at C-23. The tritium-labeled analog was synthesized in high radiochemical purity with a specific activity of 472 mCi/mmol. Copyright © 1999 John Wiley & Sons, Ltd.

Synthesis of deuterium labeled 2,4-dipyrrolidinylpyrimidine as a chemical probe for P450 mediated oxidation of tirilazad mesylate

Selective deuterium labelled pyrrolidinylpyrimidine analogs were synthesized to provide a probe for the metabolite identification of Tirilazad. Synthesis of 2-[D8]-pyrrolidinyl-4-pyrrolidinylpyrimidine (1) and 4-[D8]-pyrrolidinyl-2-pyrrolidinylpyrimidine (2) was accomplished by reaction of pyrrolidine (3) with 2,4-dichloropyrimidine (4), separation of the two reaction products (5 and 6) and reaction of these products with [D8]pyrrolidine (7). [D16]- 2,4-dipyrrolidinylpyrimidine (8) was prepared by reaction of [D8]pyrrolidine (7) with 2,4-dichloropyrimidine (4). © 1998 John Wiley & Sons, Ltd.

Synthesis of deuterium labeled 2,4-dipyrrolidinylpyrimidine as a chemical probe for P450 mediated oxidation of tirilazad mesylate

Synthesis of deuterium labeled 2,4-dipyrrolidinylpyrimidine as a chemical probe for P450 mediated oxidation of tirilazad mesylate

Synthesis of deuterium and tritium labelled 7-hydroxy- and 7-oxosterols

Deuterium and tritium 3,7-bis-labelled 7-hydroxysterols 3–5 were prepared by reduction of the 3,7-dioxosterols 1, 2 with NaB2H4 and NaB3H4. Regioselective oxidation of the deuterium 3,7-bis-labelled 7-hydroxysterols 3, 4 with CrO3/DMP led to the 3-labelled 7-oxosterols 6, 7. The 3,7-dioxosterols 1, 2 were synthesized starting from cholesterol and β-sitosterol. © 1998 John Wiley & Sons, Ltd.

Synthesis of 9-cis-retinoic acid and C-20-[3H3C]-9-cis-retinoic acid with high specific activity

The synthesis of 9-cis-retinoic acid starting from 2,2,6-trimethylcyclohexanone is described. The same methodology was extended for the synthesis of deuterium and tritium labeled 9-cis-retinoic acid with high specific activity (73 Ci/mmol). In this methodology, a Grignard reaction was utilized for introducing three tritium atoms simultaneously in the final synthetic steps. © 1997 John Wiley & Sons, Ltd.

Synthesis of deuterium- and tritium-labeled 4-methoxy-6-amino-pyrimido[4,5,b](1,4)-thiazine hydrochloride

Synthesis of deuterium- and tritium-labeled 4-methoxy-6-amino-pyrimido[4,5,b](1,4)-thiazine hydrochloride

Synthesis of deuterium labelled analogues of very long chain fatty acids C22:0, C24:0 and C26:0 for use as internal standards in stable isotope dilution analysis

Synthesis of deuterium labelled analogues of very long chain fatty acids C22:0, C24:0 and C26:0 for use as internal standards in stable isotope dilution analysis

Synthesis of deuterium labelled analogues of pristanic acid and phytanic acid for use as internal standards in stable isotope dilution analysis

Synthesis of deuterium labelled analogues of pristanic acid and phytanic acid for use as internal standards in stable isotope dilution analysis

General Discussion I Evening Session, December 6, 1983

HepatologyVolume 4, Issue S2 p. 115S-123S ArticleFree Access General Discussion I Evening Session, December 6, 1983 First published: September/October 1984 https://doi.org/10.1002/hep.1840040820AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 McBain EL, Hutchinson E. Solubilization and related phenomena: physical chemistry. New York: Academic Press, 1955: 84– 109. 2 Mukerjee P, Mysels KJ. Critical micelle concentrations of aqueous surfactant systems. Washington DC: United States Government Printing Office, 1971. 3 Igimi H, Carey MC. pH–solubility relations of chenodeoxycholic and ursodeoxycholic acids: physical–chemical basis for dissimilar solution and membrane phenomena. J Lipid Res 1980; 21: 72– 89. 4 Ekwall P, Rosendahl T, Lofman N. Studies on bile acid salt solutions. I. The dissociation constants of the cholic and deoxy–cholic acids. Acta Chem Scand 1957; 11: 590– 598. 5 Small DM. The physical chemistry of the cholanic acids. In: PP Nair, D Kritchevsky, eds. The bile acids, chemistry, physiology and metabolism. New York: Plenum Publishing Co., 1971: 249– 356. 6 Back E, Steenberg B. Simultaneous determination of ionization constant, solubility product and solubility for slightly soluble acids and bases. Electrolytic constants for abietic acid. Acta Chem Scand 1950; 4: 810– 815. 7 Cistola DP, Small DM, Hamilton JA. Ionization behavior of aqueous short–chain carboxylic acids: a carbon–13 NMR study. J Lipid Res 1982; 23: 795– 799. 8 Parks JS, Cistola DP, Small DM, et al. Interactions of the carboxyl group of oleic acid with bovine serum albumin: a 13C NMR study. J Biol Chem 1983; 258: 9262– 9269. 9 Hamilton JA, Cistola DP, Morrisett JD, et al. C NMR studies of the interaction of myristic acid with bovine serum albumin. Proc Natl Acad Sci (in press) 10 Hachey DL, Szczepanik PA, Berngruber OW, et al. Syntheses with stable isotopes: synthesis of deuterium and 13C–labeled bile acids. J Labelled Compounds 1974; 9: 703– 719. 11 Roda A, Hofmann AF, Mysels KJ. The influence of bile salt structure of self–association in aqueous solutions. J Biol Chem 1983; 258: 6362– 6370. 12 Mukerjee P, Mysels KJ, Kapauan P. Counterion specificity in the formation of ionic micelles—size, hydration, and hydrophobic bonding effects. J Phys Chem 1967; 71: 4166– 4175. 13 Moore EW, Ross JW Jr. Cationic glass electrode response in aqueous solutions of sodium and potassium chloride. Science 1965; 148: 71– 72. 14 Moore EW, Verine HJ. Pancreatic calcification: formation constants of CaHCO3+ and CaCO3 complexes determined with Ca++ electrode. Am J Physiol 1981; 4: G182– G190. Volume4, IssueS2September/October 1984Pages 115S-123S ReferencesRelatedInformation

Synthesis of deuterium and tritium labelled phenyl glycine

A new method of synthesis of phenyl glycine labelled with deuterium and tritium was elaborated. Labelled phenyl glycine was obtained by isotope exchange method between phenyl glycine and deuterated or tritiated water at elevated temperature in hydrochloric acid medium using K2PtCl4 as a catalyst. 37 GBq /1 Ci/ HTO was used for the synthesis of tritiated phenyl glycine and labelled product with specific activity of 185 MBq/mole /5 mCi/mole/ was obtained.

Synthesis of deuterium- and tritium-labeled 4-hydroxyandrostene-3,17-dione, an aromatase inhibitor, and its metabolism in vitro and in vivo in the rat

The metabolism of the aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) was studied in vitro and in vivo in the rat. To accomplish this, deuterium- and tritium-labeled 4-OHA were prepared from 4-hydroxyandrosta-4,6-diene-3,17-dione. The latter was synthesized from 4-androstene-3,17-dione. Using deuterated 4-OHA in in vitro incubations of rat ovarian microsomes, 4-hydroxytesterone (4-OHT) was identified by gas chromatography/mass spectroscopy as the major metabolite. 4-OHT constituted approximately 20% of the total radioactivity from [6,7- 3H]-4-OHA in the ovarian microsomal incubations. Conversion of [6,7- 3H]-4-OHA to 4-hydroxyestrone was approximately 0.1%. The major metabolite of [6,7- 3H]-4-OHA in vivo identified in the free, neutral fraction of rat blood was 3β-hydroxyandrostane-4,17-dione. This metabolite accounted for approximately 5% of the total radioactivity in the blood, whereas 4-OHT accounted for only 0.1%. 4-OHT inhibited in vitro ovarian aromatization by 59%, but 3β-hydroxyandrostane-4,17-dione had little effect. It was concluded that the in vivo effects of 4-OHA previously reported are largely due to its own activity although additional effects of its metabolic products cannot be excluded.

Quantitative analysis of two dinor urinary metabolites of prostaglandin I 2

The synthesis of deuterium- and tritium-labeled analogs of 2,3-dinor-6-keto-prostaglandin F 1α and of 6,15-diketo-13,14-dihydro-2,3-dinor-prostaglandin F 1α is described. These analogs were used as internal standards in the assay of the corresponding unlabeled metabolites in human urine by stable isotope dilution and combined gas chromatography-mass spectrometry. In male subjects the 24-h urinary excretion of the two metabolites was found to be 719 ± 264 and 314 ± 115 ng, respectively. The method offers a noninvasive approach to the study of prostaglandin I 2 synthesis in man.

Synthesis of deuterium and carbon-13 labelled lipids

Methods of preparing deuterated fatty acids by exchange and reduction, reaction with small deuterated compounds and synthesis using deuterated intermediates and biological synthesis are discussed. About 100 deuterated fatty acids are listed. Synthesis of a number of deuterated glycerides and phospholipids are also described. Preparations of twenty [ 13C]fatty acids and a few [ 13C]phospholipids are considered.