Detonation nanodiamonds biofunctionalization and immobilization to titanium alloy surfaces as first steps towards medical application

• Juliana P. L. Gonçalves,
• Afnan Q. Shaikh,
• Manuela Reitzig,
• Daria A. Kovalenko,
• Jan Michael,
• René Beutner,
• Gianaurelio Cuniberti,
• Dieter Scharnweber and
• Jörg Opitz

Beilstein J. Org. Chem. 2014, 10, 2765–2773, doi:10.3762/bjoc.10.293

• ]. Toxicity has not been observed so far, so it has gained particular interest in biological and medical applications [8][9]. A number of publications on single cell labeling with nanodiamond particles [10][11][12] and use in therapeutic delivery were reported [13][14][15]. In such way, the low or non

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• bioactive metabolites and selective labeling of proteins and other biomacromolecules. A common structural motif for such probes consists of a reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation between terminal alkynes and azides to a reactive headgroup. Here we introduce the

• introduced in this field and is still widely used in protein labeling [2]. Later, fluoresceins and rhodamines found applications in this area as well because of advantageous UV–vis absorption maxima (480–600 nm) and more bathochromic emission wavelengths (510–615 nm) [3]. A successful class of fluorophores

• also used for probing in life science comprises the heterocyclic thiazoles. This structural element can be found in commercial products, such as thiazole orange, SYBR® Green I or TOTO®, which are, e.g., used for DNA labeling. In these compounds the thiazole ring is part of a benzothiazole. We set out

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• higher fluorescence staining of cell-surface glycoconjugates, the glucosamine derivative gave higher labeling efficiency with protein preparations containing also intracellular proteins. Keywords: bioorthogonal chemistry; carbohydrates; cyclopropenes; inverse-electron-demand Diels-Alder reactions

• bioorthogonal labeling reactions that allow visualization [5][6]. Whereas in the first report on glycan labeling by this approach the ketone–hydrazide ligation was employed [7], later investigations mainly relied on the Staudinger ligation [8] and azide–alkyne [3 + 2] cycloaddition (copper-catalyzed [9][10] or

• fact that it can be orthogonal to the azide–alkyne cycloaddition [22][26][27] which allows dual labeling of two different sugars within one experiment [19][21][23][24]. Among the dienophiles mentioned above, strained cyclopropenes have the highest reaction rates for DAinv reactions with tetrazines and

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• completion of the synthesis, the N-terminal Fmoc group was removed and the free amino group was capped by acetylation. The acpcPNA on the solid support was spilt to 0.5 µmol portions for a further labeling experiment and treated with 1:1 dioxane/aqueous NH3 at 60 °C overnight to remove the nucleobase- and

Photo, thermal and chemical degradation of riboflavin

• Muhammad Ali Sheraz,
• Sadia Hafeez Kazi,
• Sofia Ahmed,
• Zubair Anwar and
• Iqbal Ahmad

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

• regarding the stability and degradation of a particular drug is pharmaceutically significant in the determination of its therapeutic outcomes, adverse effects, handling, packaging and labeling protocols, etc. [5][6][7][8][9]. The most common approach to cope with the problem of photosensitivity is the use

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• , primary and secondary alcohols undergo reaction under generally mild reaction conditions. Correspondingly, 1-alkoxy-1H-7-azabenzotriazoles were synthesized from At-OTs. Mechanistically, there are three pathways by which these peptide-coupling agents can react with alcohols. From 31P{1H}, [18O]-labeling

• the NMR experiments, this did not necessarily exclude pathway a. Thus, we decided to pursue a second line of investigation via [18O]-labeling. For this experiment, we prepared PhCH2[18O]H via a known procedure [31]. As shown in Scheme 3, we reasoned that exclusive reaction via pathway a should produce

• occurs via pathways b and c. A comparable [18O]-labeling experiment was conducted with Bt-OTs, where again no incorporation of the label was observed in the product, and the ratio of the peak areas [M + 2]+/[M]+ was 0.014. These results showed that both reagents, BOP and Bt-OTs, appear to react via

Syntheses of ¹⁵N-labeled pre-queuosine nucleobase derivatives

• Jasmin Levic and
• Ronald Micura

Beilstein J. Org. Chem. 2014, 10, 1914–1918, doi:10.3762/bjoc.10.199

• pathway of the hypermodified tRNA nucleoside queuosine (Que). The core structure of preQ1 is represented by 7-(aminomethyl)-7-deazaguanine (preQ1 base). Here, we report the synthesis of three preQ1 base derivatives with complementary 15N-labeling patterns, utilizing [15N]-KCN, [15N]-phthalimide, and [15N3

• derivatives with complementary 15N-labeling patterns (Scheme 1). The synthesis of preQ1 base has been described first in 1979 by Goto and coworkers from 2-methylthio-6-methoxy-7-methyl-7-deazapurine in 13 steps [9]. Another early, but more efficient procedure was reported by Nishimura in 1988 based on the

• pathway to the preQ1 derivatives with the three complementary 15N labeling patterns depicted in Scheme 1. For this undertaking we considered Carell’s synthesis [11] of preQ1 base as a solid foundation that we intended to adapt and modify accordingly, under the premises of efficacy and cost-minimization

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• previously [39]. Fluorescein-labeled FITC-HisHis was obtained by labeling of Cys-His-Cys with fluorescein isothiocyanate, which was achieved by using an Fmoc-protected oligo(ethylene glycol) spacer synthesized in four steps from commercially available ethylenediamine (see Supporting Information File 1). The

Substitution effect and effect of axle’s flexibility at (pseudo-)rotaxanes

• Friedrich Malberg,
• Jan Gerit Brandenburg,
• Werner Reckien,
• Oldamur Hollóczki,
• Stefan Grimme and
• Barbara Kirchner

Beilstein J. Org. Chem. 2014, 10, 1299–1307, doi:10.3762/bjoc.10.131

• , blue nitrogen atoms, orange carbon atom and hydrogen atoms are given in white. The labeling according to the substitution is given in bold letters. Structures below will be denoted 4@1 (left) and 5@1 (right). Molecular geometry of one rotaxane optimized in periodic boundaries at the PBE-D3/1000 eV

• Figure 2). Distances in parentheses denote the corresponding length to the heavy (non-hydrogen) atom. Interaction energies Eint for the different pseudorotaxane systems, labeling see Figure 1. The first two columns list the substituents succeeded by their effects (mesomeric or inductive). The last line

• gives the values for the di-phenyl structures. In the last column, the Hammett-parameters are given. Hydrogen bond distances in Å for the different pseudorotaxane systems, for labeling see Figure 2. The second and third last lines show the substitution at the meta-position. Interaction energies Eint for

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• the sensitivity of the nitroxide group of TOAC [129]. Koglin et al. used the photo-cleavable protecting group Nvoc for selective 3H-labeling of full length NPY. Here, lysine residues as well as the free N-terminus of resin-bound peptide, which should not be radio-labeled, were protected with Nvoc

• . Following resin cleavage, radio labeling was performed with NHS-[2,3-3H]propionate (Figure 5) by the Bolton–Hunter reaction. Then, the Nvoc protecting groups could be removed by irradiation with UV light to obtain the fully deprotected, radio-labeled peptide [130]. Biotin and fluorophores such as CF (5(6

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• the AFM results. Concentrations of spin labels were obtained from the simulations fitted to the experimental data and used to derive the degree of labeling. We found that 1% of incorporated thymidines were replaced by the spin labeled analogue in PCR when linear strands as well as networks were formed

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• for carbohydrate and peptide chemistry. Therefore, sugar units are introduced by side-chain ligation and labeling strategies on the peptide scaffold or were established by incorporation of sugar-β-amino acids by solid-phase peptide synthesis (SPPS) [36][37]. Sugar amino acid building blocks have

Staudinger ligation towards cyclodextrin dimers in aqueous/organic media. Synthesis, conformations and guest-encapsulation ability

• Malamatenia D. Manouilidou,
• Yannis G. Lazarou,
• Irene M. Mavridis and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 774–783, doi:10.3762/bjoc.10.73

• groups and readily introduced into many and different “soft” substrates, the mild reaction conditions, the high yields of the products, and the absence of a catalyst. Numerous applications of linker 2 involving labeling of biomolecules with recognition sites in aqueous media in vitro and on live cells

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• possible (Figure 2). The labeling scheme of the tautomers of 5b uses an E to indicate the (en)ol form and an O to indicate the oxo form. However, more tautomeric forms of the ester species are theoretically possible as the C-4 substituent can also be involved in tautomerism. For instance, additional

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• substituted N- or O-heterocycles in high yields (Scheme 33) [76]. Deuterium labeling experiments unambiguously demonstrated the anti-functionalization of the double bond and the use of neutral gold complexes suggested that [Au(I)] oxidation took place prior of C–X bond formation. The same team also reported

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• . erecta Pd e21 using isotope-labeling experiments that revealed its precursor molecules to be glucose-derived erythrose-4-phosphate (10) and phosphoenol-pyruvate (11, Scheme 1). Due to the observed scrambling of the expected labeling pattern in 13, its biosynthesis has to proceed via a symmetrical

Structure of 1,5-benzodiazepinones in the solid state and in solution: Effect of the fluorination in the six-membered ring

• Marta Pérez-Torralba,
• Rosa M. Claramunt,
• M. Ángeles García,
• Concepción López,
• M. Carmen Torralba,
• M. Rosario Torres,
• Ibon Alkorta and
• José Elguero

Beilstein J. Org. Chem. 2013, 9, 2156–2167, doi:10.3762/bjoc.9.253

• % probability) of 1, showing the X-ray labeling of the asymmetric unit. View of the zigzag chain formed in 1, showing the H-bond and F–F interactions. ORTEP plot (20% probability) of 2, showing the X-ray labeling of the asymmetric unit. Packing of 2 showing the F–F contacts along the chain (orange) and the π–π

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• subdivided into cytochalasins [41] (phenylalanine), chaetoglobosins [45][46] (tryptophan), aspochalasins [47] (leucine), pyrichalasins [48] (tyrosine) or alachalasins [49][50] (alanine). The biosynthesis of cytochalasans was established on the basis of various isotope labeling experiments using cytochalasin

• relationship between these three classes [87][96]. The biosynthesis of aristolochic acid I (117) was elucidated via labeling experiments and is depicted in Scheme 14 [97][98][99][100]. First, two molecules of the amino acid L-tyrosine (98) are transformed to (R)-orientaline (121) in a similar fashion as

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• deuterium labeling experiments supports a 1,4-hydride shift of the resulting allyl cationic intermediates because a complete deuterium transfer is observed. We tested the reaction on various acetal substrates bearing a propargyl acetate, giving 4-methoxy-5-alkylidenecyclopent-2-en-1-ones 4 via a degradation

• the product without deuterium content (Scheme 2, reaction 2). The results of these labeling experiments reveal a 1,4-hydrogen shift [20][21][22] in the d1-1a→d1-4a transformation. Scheme 3 shows a plausible mechanism to rationalize the transformation of the allenyl acetal 1e into the observed

• cyclopentenone 4e. The deuterium labeling experiment of the d1-1a→d1-4a transformation (Scheme 2, reaction 1) indicates that one methylene proton of 4a is derived from the original acetal group. Accordingly, we postulate a 1,4-hydride shift [21][22] for the intermediate transformation B→C. We excluded an

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• changes in reductive couplings of alkynes and 3-oxygenated epoxides. Enyne reductive coupling with 1,2-epoxyoctane. Synthesis of dithiane by Claisen rearrangement. Deuterium labeling reveals that the allylic/benzylic site is most acidic. Oxy-Michael addition to δ-hydroxy-α,β-enones. Synthesis of

Electron self-exchange activation parameters of diethyl sulfide and tetrahydrothiophene

• Martin Goez and
• Martin Vogtherr

Beilstein J. Org. Chem. 2013, 9, 1448–1454, doi:10.3762/bjoc.9.164

• species, an ”automatic” labeling with nonequilibrium magnetizations is also feasible by utilizing the CIDNP [5][6][7][8][9][10] effect (chemically induced dynamic nuclear polarization). CIDNP arises through a complex interplay of nuclear-spin-selective intersystem crossing and electron-spin-selective

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• filled by an agostic interaction prior to the C–H bond activation. Intermediate 53 evolves through a σ-CAM process, whereas intermediate 54 undergoes oxidative addition and reductive elimination processes. The release of methane and dimethylsulfide yields 55. Further studies including labeling

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

• methoxy substituent with little effect on binding affinity (Table 2). Derivative 44d, which showed good affinity towards Aβ aggregates in vitro (Ki = 6.0 ± 1.5 nM), has been radiolabeled to give N-[11C]methylamino-4'-hydroxystilbene ([11C]44d), and this compound shows excellent labeling of Aβ plaques in

• vitro Aβ labeling agents, the [99mTc] analogues 83b and 84b exhibited problems in pharmacokinetic studies in vivo. Compound 83b showed sufficient initial uptake (1.34% ID/g at 2 min), but delayed washout (0.65% ID/g at 60 min) in normal mice, while 84b was unable to cross the BBB to a sufficient degree

• was able to stain both SPs and NFTs in vitro. In normal mice, this compound showed rapid uptake (4.8% ID/g at 2 min) and fast washout (0.2% ID/g at 60 min). In vivo plaque labeling in APP transgenic mice was also successful [82]. Using similar chemistry as described above, a series of iodinated 2

Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway

• Jessica L. Bell,
• Andrew J. Haak,
• Susan M. Wade,
• Yihan Sun,
• Richard R. Neubig and
• Scott D. Larsen

Beilstein J. Org. Chem. 2013, 9, 966–973, doi:10.3762/bjoc.9.111

• , click ligation of a fluorescent dye, and gel electrophoresis revealed specific labeling of a single 24 kDa band that could be blocked with an active competitor. Future work will focus on identifying the labeled protein(s). Keywords: CCG-1423; click ligation; photoaffinity labeling; Rho pathway

• kDa (as indicated by the white box) that was competed off by 29 and does not appear without UV treatment, suggesting that it is a specific binding protein that has been successfully photolabeled. Although the level of fluorescent labeling in the non-UV-irradiated control lanes 3 is clearly diminished

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

• sulfur source for the MeSH volatiles, whereas incorporation of labeling from sulfate was not observed. Moreover, the utilization of selenite and selenate salts by marine alphaproteobacteria for the production of methylated selenium volatiles was explored and resulted in the production of numerous

• strain of DSS-3. The incorporation rates of the deuterium labeling into the MeSH-derived volatiles were reduced (64% for 1) in comparison to the wild type strain (95%) and the ratio of the cleavage pathway increased to 35% (Figure 4B). The incorporation of isotopic labeling from [2H6]DMSP by the dmdA

• GC–MS. No incorporation of the 34S-labeling from sulfate or thiosulfate into the MeSH-derived volatiles was observed, pointing strongly away from a significant involvement of sulfate reduction in the biosynthesis of MeSH. Instead, feeding of [methyl-2H3]methionine led to an effective incorporation of