Isotopically labeled sulfur compounds and synthetic selenium and tellurium analogues to study sulfur metabolism in marine bacteria

• Nelson L. Brock,
• Christian A. Citron,
• Claudia Zell,
• Martine Berger,
• Irene Wagner-Döbler,
• Jörn Petersen,
• Thorsten Brinkhoff,
• Meinhard Simon and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 942–950, doi:10.3762/bjoc.9.108

• , Germany 10.3762/bjoc.9.108 Abstract Members of the marine Roseobacter clade can degrade dimethylsulfoniopropionate (DMSP) via competing pathways releasing either methanethiol (MeSH) or dimethyl sulfide (DMS). Deuterium-labeled [2H6]DMSP and the synthetic DMSP analogue dimethyltelluriopropionate (DMTeP

• incorporation of a deuterium label into MeSH and DMS. Knockout of relevant genes from the known DMSP demethylation pathway to MeSH showed in both species a residual production of [2H3]MeSH, suggesting that a second demethylation pathway is active. The role of DMSP degradation pathways for MeSH and DMS formation

• substrate for dmd-gene-mediated liberation of MeSH even in the absence of an active dmdA gene, [2H6]DMSP was fed to a knockout mutant with a loss of the 262 kb plasmid [26]. This plasmid-cured strain exhibited the same reduced incorporation rates (32%) of deuterium label into the MeSH-derived volatiles. The

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• without further purification. β-CD was obtained from Wacker Chemie GmbH, Burghausen, Germany and was used after drying overnight with a vacuum oil pump over P4O10. N,N-Dimethylformamide (DMF) was purchased from Fluka, Germany. Dimethyl sulfoxide-d6 (99.9 atom % D) and deuterium oxide, D2O, were obtained

Quantification of N-acetylcysteamine activated methylmalonate incorporation into polyketide biosynthesis

• Stephan Klopries,
• Uschi Sundermann and
• Frank Schulz

Beilstein J. Org. Chem. 2013, 9, 664–674, doi:10.3762/bjoc.9.75

• deuterium. Relative incorporation of the D3-label into erythromycin (A) and rapamycin (B), depending on the fed concentration of rac-4. Color coding: green: no incorporation; blue: single; red: double; magenta: triple incorporation as detected by LC/ESI–MS. ESI–MS spectra of feeding experiments with an

Synthesis and stability study of a new major metabolite of γ-hydroxybutyric acid

• Ida Nymann Petersen,
• Jesper Langgaard Kristensen,
• Christian Tortzen,
• Torben Breindahl and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2013, 9, 641–646, doi:10.3762/bjoc.9.72

• glucuronidation approach that provides GHB glucuronide 2 and a deuterium-labelled analogue d4-2 of high purity suitable for analytical chemistry. In addition, we have assessed the stability of GHB glucuronide 2 by mimicking the natural pH range for urine, which is of importance in the development of new

• reported. Herein we wish to disclose the synthesis of GHB glucuronide 2 and a deuterium labelled analogue d4-2, which is required as an internal standard for chromatography. Moreover, we have assessed the stability of GHB glucuronide 2 towards aqueous hydrolysis within the pH range normally observed for

• spectrometer, respectively, by using an internal deuterium lock. Solvents were used as internal standard when assigning NMR spectra [29]. J values are given in hertz (Hz) and rounded to the nearest 0.5 Hz. Dry column vacuum chromatography (DCVC) was carried out according to the published procedure [30]. High

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• and with rate-limiting bond formation for less basic anilines is proposed based on the positive and negative ρXY values, respectively. The deuterium kinetic isotope effects involving deuterated anilines (XC6H4ND2) showed primary normal and secondary inverse DKIEs for more basic and less basic anilines

• . Keywords: anilinolysis; cross-interaction constant; deuterium kinetic isotope effects; phosphoryl transfer reaction; reactive intermediates; Y-aryl phenyl isothiocyanophosphates; Introduction The nucleophilic substitution reactions of tetracoordinate phosphorus have been studied extensively

• ). The kinetic results of the present work are discussed based on the selectivity parameters and deuterium kinetic isotope effects (DKIEs). The aim of this work is to gain further information on the substituent effects, DKIEs and mechanism of the phosphoryl transfer reactions. Results and Discussion

Intramolecular carbolithiation cascades as a route to a highly strained carbocyclic framework: competition between 5-exo-trig ring closure and proton transfer

• William F. Bailey and
• Justin D. Fair

Beilstein J. Org. Chem. 2013, 9, 537–543, doi:10.3762/bjoc.9.59

• % isolated yield. Quenching with MeOD afforded an authentic sample of 4 deuterated at the C(2) position (2H NMR: δ 5.84–5.75 (m, 1D)); the lack of a molecular ion in the GC–MS of triene 4 precluded accurate determination of the deuterium content. Addition at –78 °C of dry, oxygen-free N,N,N’,N

A peptidic hydrogel that may behave as a “Trojan Horse”

• Nicola Castellucci,
• Giorgio Sartor,
• Natalia Calonghi,
• Carola Parolin,
• Giuseppe Falini and
• Claudia Tomasini

Beilstein J. Org. Chem. 2013, 9, 417–424, doi:10.3762/bjoc.9.44

• , CT) equipped with a deuterium background corrector, Autosampler AS-72, graphite furnace Perkin-Elmer Mod. HGA-800. A Pt Lumina (Perkin-Elmer) hollow-cathode lamp was used. Ten microliters of sample was injected and the furnace was heated slowly to 2500 °C. The absorbance of atomized platinum was

Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• positioned on opposite sides of the hydrocarbon substrate due to the steric congestion at its core (note the position of NH3 throughout Figure 7), a scenario that could be probed by deuterium labeling of farnesyl diphosphate if a suitable caryolene synthase were isolated. The energetics for both pathways

Radical zinc-atom-transfer-based carbozincation of haloalkynes with dialkylzincs

• Fabrice Chemla,
• Florian Dulong,
• Franck Ferreira and
• Alejandro Pérez-Luna

Beilstein J. Org. Chem. 2013, 9, 236–245, doi:10.3762/bjoc.9.28

• intermediate formation of an alkylidene zinc carbenoid as deuterated 4aa-D was produced (Table 1, entry 2). As previously noted in the case of similar 1,4-addition/carbozincation sequences [37][38], deuterium incorporation was nearly quantitative for the Z isomer, and much lower for the E one. More

• unexpectedly, however, 40% of alkylidenetetrahydrofuran 5a, wherein the bromine atom had been substituted by an ethyl group, was also isolated as a 79:21 Z/E mixture. Deuterium labeled 5a-D was produced following hydrolysis with D2O (Table 1, entry 2), thereby showing that an alkylidenezinc intermediate was

• possibility to account for the formation of 7 could be the reaction of the dialkylzinc reagent with enoate 8 arising from a prior substitution of bromoalkyne 3a with the dialkylzinc reagent (Scheme 3, path b). Both the diastereoselectivity and the levels of deuterium incorporation are very close to those

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

Cyclodextrin-induced host–guest effects of classically prepared poly(NIPAM) bearing azo-dye end groups

• Gero Maatz,
• Arkadius Maciollek and
• Helmut Ritter

Beilstein J. Org. Chem. 2012, 8, 1929–1935, doi:10.3762/bjoc.8.224

• purification. RAMEB-CD and β-CD were obtained from Wacker Chemie GmbH, Burghausen, Germany and were used after being dried overnight with a vacuum oil pump over P4O10. N,N-Dimethylformamide (DMF) was purchased from Fluka, Germany. Dimethylsulfoxide-d6 (99.9 atom % D) and deuterium oxide, D2O were obtained from

Alkenes from β-lithiooxyphosphonium ylides generated by trapping α-lithiated terminal epoxides with triphenylphosphine

• David. M. Hodgson and
• Rosanne S. D. Persaud

Beilstein J. Org. Chem. 2012, 8, 1896–1900, doi:10.3762/bjoc.8.219

• (48 h) or in the presence of increased Ph3P (2 equiv), or TMEDA (1 equiv) or LiBr (2 equiv) as additives were all less effective. The use of a proton (deuterium) source as the electrophile to trap an epoxide-derived ylide prepared by using LTMP was next examined. This was anticipated to provide a base

• dodecene (14) (41%, 50% D [46]) after reaction with CD3OD (Scheme 6), where the deuterium incorporation was nonstereoselective [44]. Modest deuterium incorporation suggests partial collapse of the intermediate β-lithiooxy ylide occurs under the conditions of its generation, by elimination of Ph3PO after or

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• performed for the prenylation of tryptophan and tryptamine derivatives, as well as peptides containing tryptophan. Taking into account some experimental evidence obtained from the use of 2-methyl or 2-deuterium-substituted indoles and from [1,1,1-D3]3-methyl-2-butene, the mechanism shown in Scheme 8 was

Organocatalytic C–H activation reactions

• Subhas Chandra Pan

Beilstein J. Org. Chem. 2012, 8, 1374–1384, doi:10.3762/bjoc.8.159

• a deuterium radical from THF-d8 to provide 23. The authors found a low conversion (2%) for 23 in the absence of Ph-phen indicating the involvement of Ph-phen in the radical generation. The authors explained that Ph-phen can act as a single-electron-transfer (SET) mediator because it has a low lying

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• that the simple method will allow us to prepare a variety of α-glycolipid antigens other than GGPLs and to prove their biological significance [43]. By the 1H NMR conformational analysis, which was based on our former studies on deuterium-labeled sn-glycerols and sugars, we have proven that GGPL-I and

• protons (HproR and HproS) was performed on the basis of our preceding studies on deuterium-labeled glycerols [35][36][37] and α(1→6)-linked disaccharides [38][39][40]. Distributions of gg, gt and tg-conformers in 3-substituted sn-glycerols at 11 mM in solutions of CDCl3 and CD3OD (10:1) at 298 K

Double N-arylation reaction of polyhalogenated 4,4’-bipyridines. Expedious synthesis of functionalized 2,7-diazacarbazoles

• Mohamed Abboud,
• Emmanuel Aubert and
• Victor Mamane

Beilstein J. Org. Chem. 2012, 8, 253–258, doi:10.3762/bjoc.8.26

• internal deuterium lock. Chemical shifts are quoted in parts per million (ppm) downfield of tetramethylsilane. Coupling constants J are quoted in Hz. Mass spectra with electronic impact (MS–EI) were recorded from a Shimadzu QP 2010 apparatus. High resolution mass spectra were recorded from a Bruker

Thermodynamic and kinetic stabilization of divanadate in the monovanadate/divanadate equilibrium using a Zn-cyclene derivative: Towards a simple ATP synthase model

• Hanno Sell,
• Anika Gehl,
• Frank D. Sönnichsen and
• Rainer Herges

Beilstein J. Org. Chem. 2012, 8, 81–89, doi:10.3762/bjoc.8.8

• of 100 mM and 50 mM of sodium hydroxide. They were prepared by dissolving the appropriate amount of buffer and sodium hydroxide in 90% deionized water and 10% deuterium oxide. To obtain the vanadate stock solution (50 mM) sodium orthovanadate (92.0 mg) was dissolved in the respective buffer solution

• orthovanadate, and the concentration of the Zn-benzylcyclene 1 stock solution was 10 mM. For each experiment 60 μL of the vanadate stock solution, 400 μL of the respective buffer stock solution, and 600 μL of the Zn-benzylcyclene 1 stock solution were mixed with 100 μL deuterium oxide and 840 μL deionized water

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• . Incorporation of deuterated precursors was observable through the increased molecular masses and m/z ratios of certain fragment ions that could be used to localise the deuterium incorporation. One advantage of using deuterated precursors is that deuterium incorporation results in a decrease in the retention

• -methylpentanoic acid proceeds with the loss of one deuterium, and accordingly, nine deuterium atoms were incorporated into 3, as indicative by a shift of the molecular ion of 3 from m/z = 116 to m/z = 125 (compare Figures S2A and S2B of Supporting Information File 1). The fragment ion at m/z = 101, arising

• isopropyl group (m/z = 43 and m/z =143) shifted to m/z = 50 and m/z = 145 in agreement with the deuterium labelling of this portion of the molecule. The labelling was also introduced into the iso-odd FAMEs 102 and 103 (Figures S3C to S3F of Supporting Information File 1) and the higher homologue methyl 15

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• -arylated benzoxazole after a reductive elimination step (Scheme 19a). Deuterium-incorporation experiments and DFT calculations highly support this pathway as well as the successful palladium-catalyzed arylation of the O-silylated 2-isonitrilephenolate (Scheme 19b). Last year, Strotman and Chobanian

• oxazole-4-carboxylate employing strong Cs2CO3, K3PO4 or DBU bases, through deuterium-incorporation experiments in dioxane and toluene solvents, which led in both cases to the production of C2 and C5 deuterated ethyl oxazole-4-carboxylate [64]. Thus, an electrophilic substitution-type mechanism is

Directed aromatic functionalization in natural-product synthesis: Fredericamycin A, nothapodytine B, and topopyrones B and D

• Charles Dylan Turner and
• Marco A. Ciufolini

Beilstein J. Org. Chem. 2011, 7, 1475–1485, doi:10.3762/bjoc.7.171

• Snieckus conditions. For instance, treatment with five equivalents (as opposed to the customary 1.05 equivalents) of sec-BuLi–TMEDA complex for a prolonged period of time resulted in no incorporation of deuterium upon quenching with CD3OD. The reasons for this remain unknown to this date. Various

• groups can surely sequester organo–Li species at least as effectively as the 2,4-dimethoxy-3-chloro arrangement present in 57. In any event, ortho-deprotonation was ultimately achieved by the reaction of 57 with the more basic t-BuLi–TMEDA complex (1 equiv, 3 h, –78 °C; complete deuterium incorporation

Directed ortho,ortho'-dimetalation of hydrobenzoin: Rapid access to hydrobenzoin derivatives useful for asymmetric synthesis

• Inhee Cho,
• Labros Meimetis,
• Lee Belding,
• Michael J. Katz,
• Travis Dudding and
• Robert Britton

Beilstein J. Org. Chem. 2011, 7, 1315–1322, doi:10.3762/bjoc.7.154

• the eventual selection of a 2:1 mixture of hexane/ether as the most favorable reaction solvent for the formation of the tetralithio intermediate 8 [23]. Despite the high level of deuterium incorporation (92%) observed in the reaction of the tetralithio intermediate 8 with D2O (Scheme 1), this result

• was not observed for reactions with other electrophiles (see below). In addition, the products from deuterium quenching studies were often accompanied by the formation of varying amounts of the deoxybenzoin 10, which presumably derives from reaction of an alkoxide function in 8 with D2O, followed by

Use of mixed Li/K metal TMP amide (LiNK chemistry) for the synthesis of [2.2]metacyclophanes

• Marco Blangetti,
• Patricia Fleming and
• Donal F. O'Shea

Beilstein J. Org. Chem. 2011, 7, 1249–1254, doi:10.3762/bjoc.7.145

• selective site of metalation should be the more acidic 2-methyl position [26]. This was confirmed by 2H NMR, which showed that incorporated deuterium was above 90% in the 2-methyl position with less than 10% in the 4-methyl group and no detectable aryl deuteration (Figure 2). A similar experiment was

• deuteration gave the di-deuterated product D2-6f. 2H NMR analysis showed no aryl or bridging methylene deuteration, with deuterium incorporated only into the two non-equivalent benzylic methyl positions (Figure 3). With the benzylic metalation confirmed, the second step to complete the [2.2]metacyclophane

Selectivity in C-alkylation of dianions of protected 6-methyluridine

• Ngoc Hoa Nguyen,
• Christophe Len,
• Anne-Sophie Castanet and
• Jacques Mortier

Beilstein J. Org. Chem. 2011, 7, 1228–1233, doi:10.3762/bjoc.7.143

• (evaluated by NMR) with exclusive deuterium incorporation at the C6 position. However, almost complete recovery of the starting material was observed when dianion 11 was allowed to react with 4-bromobut-1-ene [15]. Lithium–copper transmetallation was also attempted. Unfortunately, addition of 0.25 equiv of

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• sp3-hybridized C–H bond can be achieved by undergoing 1,3-addition to a vinyl–carbenoid intermediate [142]. The bicyclo[3.2.1]oct-6-en-2-ones 265 and 267 could be synthesized stereoselectively by this method. Deuterium labeling experiments indicated the cyclization involved an unprecedented 1,3

• via oxidative gold catalysis and provided expedient access to various substituted N- or O-heterocycles (344–351) (Scheme 57). Deuterium labeling experiments were carried out to unveil the reaction mechanism. The results established the anti nature of the alkene functionalization and the indispensable

The role of silver additives in gold-mediated C–H functionalisation

• Scott R. Patrick,
• Ine I. F. Boogaerts,
• Sylvain Gaillard,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2011, 7, 892–896, doi:10.3762/bjoc.7.102

• stoichiometric reaction between Ag2O and the substrate displayed substitution of one of the protons. However, deuterium incorporation experiments were unsuccessful and mass spectrometry on the product was inconclusive. The reaction depicted in Scheme 2 was performed using a neutral gold(I)-NHC complex. The