Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• methods they are available from 3- or 4-hydroxyglutamic acids by direct hydroxy to fluoride displacement [91][123][124]. Deuterium- [72] and tritium-labelled [125] glutamic acids have also been prepared from 4-hydroxyglutamic acids via 4-mesyloxy derivatives. And finally reduction of the ethoxycarbonyl

Volatiles from the hypoxylaceous fungi Hypoxylon griseobrunneum and Hypoxylon macrocarpum

• Jan Rinkel,
• Alexander Babczyk,
• Tao Wang,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 2974–2990, doi:10.3762/bjoc.14.277

• of Scheme 2. Note that because of an isotope effect the isotopomers of 24 can be separated by gas chromatography depending on their deuterium content [34][35], which makes the usage of (methyl-2H3)methionine superior to the usage of 13C-labelled methionine that would not have led to chromatographic

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• CoI2(dppf) (10 mol %), Zn(OAc)2 (10 mol %), and Et4NI (10 mol %) in a mixture of CH3CN and DMF (v/v = 10:1) under an atmospheric pressure of CO2 at 40 °C. When the reaction mixture was quenched with D2O (>99% D), deuterated 17a-D was obtained in a 1H NMR yield of 80% with excellent deuterium

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• spectra were determined with a SHIMADZU RF5301 spectrometer. Deuterated phosphate buffer solutions (20 mM) of pD 7.4 for 1H NMR experiments were prepared by mixing K2DPO4 deuterium oxide solution (20 mM) and KD2PO4 deuterium oxide solution (20 mM) according to the calculated volume ratios. The pH/pD

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• made the reaction much milder than the thermally-induced reaction but also changed the rearrangement mode to an unprecedented [1,3]-manner. In addition, intermolecular and intramolecular competitive experiments using deuterium-labelled substrates resulted in no kinetic effect (Scheme 4). These results

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• for 2,3-benzotropone (12) are condensation reactions with active methylenic compounds, resulting in the formation of benzoheptafulvenoids (Figure 6). For example, Machiguchi reported that the condensation reaction of deuterium tracer 2,3-benzotropone 177 with malononitrile to yield 8,8-dicyano-2,3

Hypervalent iodine-guided electrophilic substitution: para-selective substitution across aryl iodonium compounds with benzyl groups

• Cyrus Mowdawalla,
• Faiz Ahmed,
• Tian Li,
• Kiet Pham,
• Loma Dave,
• Grace Kim and
• I. F. Dempsey Hyatt

Beilstein J. Org. Chem. 2018, 14, 1039–1045, doi:10.3762/bjoc.14.91

• -Claisen rearrangement (RICR) to describe the product selectivity they encountered [8]. More recently, exceptional progress has been made in investigating the RICR’s substrate scope (electron-donating versus electron-withdrawing substituents on PhI(OAc)2 (1a)), mechanism (deuterium labelling studies

• ] compelling evidence was shown by deuterium labelling studies supporting a concerted intramolecular mechanism (RICR) occurring rather than a stepwise intermolecular one. To corroborate their findings with our own, we investigated the HIGES reaction through crossover experiments which appear to conclude a

Chlorination of phenylallene derivatives with 1-chloro-1,2-benziodoxol-3-one: synthesis of vicinal-dichlorides and chlorodienes

• Zhensheng Zhao and
• Graham K. Murphy

Beilstein J. Org. Chem. 2018, 14, 796–802, doi:10.3762/bjoc.14.67

• processes that might not be elucidated through product analysis alone, deuterated biphenylallene [D2]-2b was subjected to the standard reaction conditions, and [D2]-3b (E/Z = 1:2) was obtained in 79% yield (Scheme 6 top, also see Supporting Information File 1). As there was no indication of deuterium

Stereochemical outcomes of C–F activation reactions of benzyl fluoride

• Neil S. Keddie,
• Pier Alexandre Champagne,
• Justine Desroches,
• Jean-François Paquin and
• David O'Hagan

Beilstein J. Org. Chem. 2018, 14, 106–113, doi:10.3762/bjoc.14.6

• explore the stereointegrity of the aforementioned reactions using enantiopure 7-[2H1]-(R)-benzyl fluoride ((R)-1, Figure 2) as a primary, yet chiral electrophile [10]. Substitution reactions of benzyl fluoride (1) will generate substituted products that retain the deuterium atom, and the degree of

• reduced under Noyori’s conditions [12] using (S,S)-Ru(DPEN)2 as catalyst and [2H2]-formic acid as the deuterium source. This afforded the corresponding 7-[2H1]-(S)-benzyl alcohol ((S)-3) in moderate yield (81%) and high ee (95%), as evidenced by 2H-PBLG-NMR. Benzyl alcohol 3 was converted to the

Hydrolysis, polarity, and conformational impact of C-terminal partially fluorinated ethyl esters in peptide models

• Vladimir Kubyshkin and
• Nediljko Budisa

Beilstein J. Org. Chem. 2017, 13, 2442–2457, doi:10.3762/bjoc.13.241

• AcGlyGlyProGlyGlyNH2 [71] and AcGlyProOMe [68] compounds when measured in deuterium oxide. For 1–5, we found the trans/cis ratios ≈ 5 for all five esters when measured in aqueous medium; the kinetic parameters of the amide rotation were also nearly identical (Table 2). We then noticed that the trans/cis ratios

• in compound 1 [74]. We examined the values of Jαβ for compounds 1–5 in a polar (deuterium oxide) and nonpolar (benzene-d6) solvents. The observed Jαβ values are consistent with those reported previously [74][83], and the value differences likely reflect a change of only a few percent due to the

• applied a simple set of equations for estimation of the diffusion coefficients of an oligomeric hydrophobic polyproline-II helix [71]. Here, we combined these equations in order to derive Equation 5, which describes diffusion as a function of molecular weight assuming pure deuterium oxide solution at 298

Fluorination of some highly functionalized cycloalkanes: chemoselectivity and substrate dependence

• Attila Márió Remete,
• Melinda Nonn,
• Santos Fustero,
• Matti Haukka,
• Ferenc Fülöp and
• Loránd Kiss

Beilstein J. Org. Chem. 2017, 13, 2364–2371, doi:10.3762/bjoc.13.233

• 60 F254 was purchased from Merck. The NMR spectra were acquired at room temperature on a Bruker Avance 400 spectrometer with 11.75 T magnetic field strength (1H frequency: 400.13 MHz, 19F frequency: 376.50 MHz, 13C frequency: 100.76 MHz, respectively) in CDCl3 or DMSO-d6 solution, using the deuterium

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• signals of acidic protons are not visible in D2O due to the fast substitution by deuterium atoms we performed 1D NMR measurements in DMSO-d6 (see Figures S15–S17, S18, S23 and Tables S5 and S6 in Supporting Information File 1). From these experiments it can be clearly seen that pyrrolic proton PTX#H4

Remarkable functions of sn-3 hydroxy and phosphocholine groups in 1,2-diacyl-sn-glycerolipids to induce clockwise (+)-helicity around the 1,2-diacyl moiety: Evidence from conformation analysis by ¹H NMR spectroscopy

• Yoshihiro Nishida,
• Mengfei Yuan,
• Kazuo Fukuda,
• Kaito Fujisawa,
• Hirofumi Dohi and
• Hirotaka Uzawa

Beilstein J. Org. Chem. 2017, 13, 1999–2009, doi:10.3762/bjoc.13.196

• ; deuterium labeling; sn-glycerol; glycerolipids; glycerophospholipids; helicity; Karplus equation; proton NMR spectroscopy; staggered conformers; Introduction Glycerophospholipids, constituting the basic elements of cytoplasm bilayer membranes, are responsible for several cell functions [1][2][3]. These

• storage in CDCl3 solution. Acquisition of the 1H NMR spectral data of H1proR and H1proS signals Each of the four glycerolipids 1–4 is dissolved in either CDCl3 or the mixed solvents containing methanol-d4 in CDCl3 (deuterium content > 99.5%) at ca. 10 mM concentrations. 1H NMR spectroscopy is measured on

18-Hydroxydolabella-3,7-diene synthase – a diterpene synthase from Chitinophaga pinensis

• Jeroen S. Dickschat,
• Jan Rinkel,
• Patrick Rabe,
• Arman Beyraghdar Kashkooli and
• Harro J. Bouwmeester

Beilstein J. Org. Chem. 2017, 13, 1770–1780, doi:10.3762/bjoc.13.171

• analysis of the obtained terpene products. Incubation of (R)-(1-13C,1-2H)GGPP with HdS resulted in the specific incorporation of the deuterium labelling into the 2α position as indicated by a deminished crosspeak in the HSQC spectrum, while the crosspeak for H2β was strongly enhanced because of the 13C

• labelling of C2 (Figure 2). Consistently, the substrate (S)-(1-13C,1-2H)GGPP gave a product with specific incorporation of the deuterium label into the 2β position. Assuming inversion of configuration at C1 for the cyclisation of GGPP to 3 as reported for several other terpene synthases [13][20][21][22

• gave a stereospecific incorporation of the deuterium labelling into H10α from (R)-(1-13C,1-2H)GPP and into H10β from (S)-(1-13C,1-2H)GPP (Figure 3), which pointed to the same absolute configuration for 3 as deduced from the experiments with the two enantiomers of (1-13C,1-2H)GGPP. Similar incubation

Theoretical simulation of the infrared signature of mechanically stressed polymer solids

• Matthew S. Sammon,
• Milan Ončák and
• Martin K. Beyer

Beilstein J. Org. Chem. 2017, 13, 1710–1716, doi:10.3762/bjoc.13.165

• modes specific to the polymer ends would be very weak. Therefore, hydrogen atoms from the terminal methyl groups were substituted with deuterium. The spectral lines originating from these CD3 groups were removed from the simulated spectra. To simulate the intensities of infrared bands in the fingerprint

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• Leadlay and co-workers applying LC−sequential and high-resolution mass spectrometry in combination with deuterium exchange experiments [54]. Instead of the additional hydroxy group proposed by the Small group, these studies provided strong evidence for mycolactone D (3) to feature an extra methyl group at

• spectrometry in conjunction with oxidative degradation and deuterium exchange experiments [56]. In spite of the challenge posed by the severely limited availability of natural material for structural analysis, Kishi and co-workers later demonstrated by total synthesis (vide infra) that the Leadlay structure

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• chromatography [24], or in capillary electrophoresis [25]. Results and Discussion NMR studies In deuterium oxide (D2O), each of the NAcTrp enantiomers induced significant chemical shift displacements (shielding) in the 1H NMR signals of the β-CD cavity protons, namely H3 (near the wider, secondary side) and H5

• orientation of the guest inside the host and the formation of the crystals per se. Experimental Materials and methods N-Acetyl-L-tryptophan (L-NAcTrp), N-acetyl-D-tryptophan (D-NAcTrp) and β-CD were obtained from Sigma-Aldrich. Deuterium oxide was a product of Deutero GmbH. NMR spectroscopy The spectra were

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• , 1 h, 25 °C) was performed in order to identify the position(s) of ring metalation of 12. In recovered (about 80%) educt, deuterium incorporation (about 40%; calculated from integrals of the 1H NMR spectrum) was observed exclusively at C-6 of the benzamide moiety (Scheme 6). It is known for decades

• of 1 h, followed by D2O quenching resulted in complete decomposition. In contrast, metalation of amide 16 under the same conditions and quenching with D2O led to the formation of the benzo[c]fluoren-7-one 17 in 38% yield. In recovered (about 20%) educt 16, deuterium incorporation (about 20

Glycoscience@Synchrotron: Synchrotron radiation applied to structural glycoscience

• Serge Pérez and
• Daniele de Sanctis

Beilstein J. Org. Chem. 2017, 13, 1145–1167, doi:10.3762/bjoc.13.114

New approach toward the synthesis of deuterated pyrazolo[1,5-a]pyridines and 1,2,4-triazolo[1,5-a]pyridines

• Aleksey Yu. Vorob’ev,
• Vyacheslav I. Supranovich,
• Gennady I. Borodkin and
• Vyacheslav G. Shubin

Beilstein J. Org. Chem. 2017, 13, 800–805, doi:10.3762/bjoc.13.80

• and a high degree of deuterium incorporation were achieved. The procedure was applied for several 4-R-1-aminopyridinium cations (R = H, Me, OMe). Keywords: deuteration; 1,3-dipolar cycloaddition; pyrazolo[1,5-a]pyridine; 1,2,4-triazolo[1,5-a]pyridine; Introduction Isotopically labeled compounds find

• broad applications in studies of chemical and biochemical reaction mechanisms and metabolism pathways. Deuterium is the most common used isotopic label in mechanistic studies. Deuterated organic compounds are widely used in biological [1] and pharmacological [2][3][4][5] investigations. In the last

• intramolecular ring closure [21][22][23][24]. The importance of these cores for medical chemistry studies suggests that isotopically labeled pyrazolo[1,5-a]pyridines and triazolo[1,5-a]pyridines could be of interest. Recently, deuterium-labeled pyridinium-N-imines were applied to mechanistic studies of the

Membrane properties of hydroxycholesterols related to the brain cholesterol metabolism

• Malte Hilsch,
• Ivan Haralampiev,
• Peter Müller,
• Daniel Huster and
• Holger A. Scheidt

Beilstein J. Org. Chem. 2017, 13, 720–727, doi:10.3762/bjoc.13.71

• wt % deuterium-depleted water. The samples were equilibrated by ten freeze-thaw cycles and transferred into 5 mm glass vials and sealed. 2H NMR measurements The 2H NMR experiments were performed on a Bruker DRX300 NMR spectrometer (Bruker BioSpin, Rheinstetten, Germany) at a resonance frequency of

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• -indanones 159a–g by a rhodium-catalyzed isomerization of racemic α-arylpropargyl alcohols 158 has been developed by Shintani, Okamoto and Hayashi (Scheme 46) [76]. By the mechanistic investigations using deuterium-labeled substrates, the authors have disclosed that the methine proton of the alcohol goes to

Biosynthetic origin of butyrolactol A, an antifungal polyketide produced by a marine-derived Streptomyces

• Enjuro Harunari,
• Hisayuki Komaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2017, 13, 441–450, doi:10.3762/bjoc.13.47

• addition, the 2H (deuterium) NMR spectrum showed deuterium signals for the methyl group (H-25, H-26, H-27) of L-valine-d8-labeled 1 (Figure 7a). The mass spectrum of the L-valine-d8-labeled 1 displayed the molecular ion with a mass increment of 6 Da (Figure 7b), corresponding to the incorporation of six

• deuterium atoms into the terminal methyl groups. Based on these results from precursor-feeding experiments, we concluded that the tert-butyl group and the adjacent methylene carbon (C-23) are derived from valine and the S-methyl carbon of methionine. It is controversial whether pivaloyl CoA is loaded onto

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• deuterium label was retained at the C-2 position bearing the D-configured methyl group (generated by module 2), while no labeling was observed at C-4 bearing the L-configured methyl group (generated by module 1). The opposite labeling pattern was obtained when biosynthesis was carried out with unlabeled

• additional epimerization step must occur in module 1 to yield the L-methyl stereochemistry present at C-4 (thus explaining the loss of deuterium from the 2-position when (2RS)-[2-2H]methylmalonyl-CoA was used, and its incorporation from solvent in the presence of unlabeled extender) (mechanism III, Figure 9

• the KR prior to ketoreduction (the alternative possibility that epimerization occurs in all modules but that the KRs select the correct isomer is excluded by the in vitro studies with DEBS 1-TE (Figure 9) [46], as no deuterium from the deuterated extender unit would have been retained in the triketide