Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• favored. • The monotosylation of 6-monoazido-β-CD (both in pyridine and Cu(II)-mediated in aqueous solution) is a primary-side process that leads to the theoretical three couples of pseudoenantiomers. Schematic representation of β-CD with glucopyranose atom numbering and with alphabetic labeling of the

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• reaction kinetics and their labeling intensities after metabolic incorporation. To determine the efficiencies by which the derivatives are metabolized to sialic acids, we synthesized and investigated the corresponding cyclopropane derivatives because cyclopropenes are not stable under the analysis

• acceptance results in the same cell-surface labeling intensity due to its superior reactivity in the DAinv reaction. Based on the high incorporation efficiency of the Cp derivative we synthesized and investigated two new Cp-modified glucosamine and galactosamine derivatives. Both compounds lead to comparable

• cyclopropene derivatives were not stable under these conditions, an observation that has also been made by Ye and co-workers [27]. Therefore, we decided to investigate the corresponding cyclopropane derivatives instead. We expected them to be stable under the DMB labeling conditions and during the preparation

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• ] have been actively studied for their fluorescent properties. Among others, also azole containing compounds of type E [28] and F [29] have been described. Similarly, to purine derivatives also 7-deazapurines are used in DNA labeling [30]. On the other hand, modified purines have found also applications

• described N(9)-alkylated-2-amino-6-triazolylpurines and 7-deazapurines as cell labeling agents for biological chemistry applications. Conclusion A group of novel and structurally related N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines was obtained, using the corresponding 2,6-diazido

• biocompatible, cell-permeable, not cytotoxic and do not influence cell proliferation. Thus, one can predict that the developed purine and 7-deazapurine derivatives possessing the novel substitution pattern may find their application also in cell labeling in the future besides the potential use as materials in

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

• ]-manner was confirmed by a crossover experiment and oxygen-18 labeling experiments. That is, the reaction of a 1:1 mixture of equally-reactive substrates 1h and 1r under the standard reaction conditions afforded only the products 2h and 2r derived from the starting materials (Scheme 3a). Thus, we

Diazirine-functionalized mannosides for photoaffinity labeling: trouble with FimH

• Femke Beiroth,
• Tomas Koudelka,
• Thorsten Overath,
• Stefan D. Knight,
• Andreas Tholey and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1890–1900, doi:10.3762/bjoc.14.163

• , Christiana Albertina University of Kiel, Niemannsweg 11, D-24105 Kiel, Germany Department of Cell and Molecular Biology, Uppsala University, Uppsala Biomedical Centre, P.O. Box 596, S-751 24 Uppsala, Sweden 10.3762/bjoc.14.163 Abstract Photoaffinity labeling is frequently employed for the investigation of

• X-ray crystallography, studies in solution add valuable information in molecular recognition studies as they take molecular dynamics as well as solvent effects into consideration. In the latter respect, photoaffinity labeling has evolved as a useful tool for studies under physiological conditions [1

• ][2][3][4]. Photoaffinity labeling requires a ligand equipped with a photolabile group, which can be converted into a highly reactive intermediate upon irradiation with light of an appropriate wavelength. This technique involves incubation of the photolabile ligand with the target protein (receptor

Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• molecules [9]. However, this method will greatly reduce the life of the column [10]. Moreover, the absence of a chromophore in most BPs lead to the employment of derivatization by an UV–vis light-absorbing or fluorescence label for detection [11][12]. However, directly labeling BPs in biological media is

• difficult because many other components can reduce the efficiency of the labeling reaction. Especially in urine, it is extraordinary challenging to achieve labelling of BPs because urine generally contains a large amount of polar compounds such as phosphates, unless these are removed in advance [7]. Ion

Natural and redesigned wasp venom peptides with selective antitumoral activity

• Marcelo D. T. Torres,
• Gislaine P. Andrade,
• Roseli H. Sato,
• Cibele N. Pedron,
• Tania M. Manieri,
• Giselle Cerchiaro,
• Anderson O. Ribeiro,
• Cesar de la Fuente-Nunez and
• Vani X. Oliveira Jr.

Beilstein J. Org. Chem. 2018, 14, 1693–1703, doi:10.3762/bjoc.14.144

• L−1 after 2 h (Figure 2). Cell death assays Flow cytometry experiments were performed in an attempt to obtain insight into the mechanism of peptide-mediated death of cancer cells. For these proof-of-concept assays, we focused on WT peptide Dec-NH2. We utilized Annexin V labeling FITC (X axis) and

Phosphoramidite building blocks with protected nitroxides for the synthesis of spin-labeled DNA and RNA

• Timo Weinrich,
• Eva A. Jaumann,
• Ute M. Scheffer,
• Thomas F. Prisner and
• Michael W. Göbel

Beilstein J. Org. Chem. 2018, 14, 1563–1569, doi:10.3762/bjoc.14.133

• measure long distances that are hardly accessible by NMR [9][10]. Furthermore, spin labeling of biopolymers can support NMR studies by paramagnetic relaxation enhancement [11][12]. For nucleic acids, spin labeling is most often achieved by covalent attachment of nitroxides. Unfortunately, the conditions

• distance. The results for all PELDOR measurements are shown in Figure S21 (Supporting Information File 1). The experimental distances are summarized in Table 1 and coincide well with values predicted from modelling. However, although the degree of spin labeling was very high in all cases, large variations

• of hemiacetals. After the annealing procedure, mean spin labeling efficiencies of 96% have been found. Samples of similar quality including TEMPO labeled cytidines are also accessible by postsynthetic modification of convertible nucleotides [8][25][26]. However, the analogous reaction forming TEMPO

Synthesis and in vitro biochemical evaluation of oxime bond-linked daunorubicin–GnRH-III conjugates developed for targeted drug delivery

• Sabine Schuster,
• Beáta Biri-Kovács,
• Bálint Szeder,
• Viktor Farkas,
• László Buday,
• Zsuzsanna Szabó,
• Gábor Halmos and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 756–771, doi:10.3762/bjoc.14.64

• retention time 16.2–16.6 min of the LC–MS chromatogram). C) LC–MS chromatogram of the GnRH-III bioconjugates after 24 h of incubation with rat liver lysosomal homogenate at 37 °C (asterisk labeling peak of the smallest Dau-containing metabolite H-K(Dau=Aoa)-OH). Cytostatic effect of the GnRH-III

Enzyme-free genetic copying of DNA and RNA sequences

• Marilyne Sosson and
• Clemens Richert

Beilstein J. Org. Chem. 2018, 14, 603–617, doi:10.3762/bjoc.14.47

• , partly because it is performed at much higher concentrations (millimolar, rather than micromolar analytes), and partly because it provides site-specific information without labeling. Labeling of an analyte as small as a mononucleotide with something other than isotopes was considered problematic, as it

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• available unmodified ONs, while the second approach first requires the synthesis of a modified unit followed by its incorporation into ON during solid-phase synthesis. However, the first approach is far less efficient than the second one because the labeling of phosphodiester linkages with diazo compounds

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• , as well as the types of linkers, need to be fine-tuned in order to obtain optimal results. In this respect, the ability to site-specifically label anywhere in the PNA molecule using a pre-formed dye-labeled monomer or a functionalized monomer that allows post-synthetic labeling is important [84

• following standard surface-hybridization protocols. The use of the solid support assay format also allows detection of DNA directly from the fluorescence signal of the CPP bound to the solid support without requiring labeling on the PNA probe [126]. Polystyrene microbeads self-assembled on patterned silicon

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• ]. The tricyclic core was synthesized as reported by Roth et al., and subsequently functionalized with a carboxylic acid handle for PNA labeling [39]. In 2003, tC [35] was synthesized bearing a 2´-deoxyribose functionality and thoroughly photophysically characterized (vide infra). tC was later

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

• compounds using labeling reagents having a hydrazide group. A hydrophilic fluorescence group Alexa Fluor 568 and polyethylene glycol-linked biotin were introduced using hydrazone formation reaction between the aldehyde group of the glutaryl-Glc linker and the hydrazide group of the labeling reagent. In

• antagonist) and the fluorescence intensity of 25 and its tetraacylated counterpart was comparable with the fluorescence of the labeling reagent alone. Aggregation-mediated fluorescence quenching was not observed which confirmed the advantage of application of highly hydrophilic linker molecules and non

• -hydrophobic labeling reagents for amphiphilic glycoconjugates such as lipid A. 1.4. Synthesis of Helicobacter pylori Kdo-lipid A substructures A Helicobacter pylori infection of the gastric mucosa causes chronic gastritis in humans and plays a pivotal role in the progression and pathogenesis of peptic ulcer

Microfluidic radiosynthesis of [¹⁸F]FEMPT, a high affinity PET radiotracer for imaging serotonin receptors

• Thomas Lee Collier,
• Steven H. Liang,
• J. John Mann,
• Neil Vasdev and
• J. S. Dileep Kumar

Beilstein J. Org. Chem. 2017, 13, 2922–2927, doi:10.3762/bjoc.13.285

• the reduction in reaction times and consumption of reagents that often result in increased radiochemical yields and rapid optimization of reaction parameters for 18F-labeling. In this paper, we report on the two-step microfluidic radiosynthesis of the high affinity partial agonist of the serotonin 1A

• nM. Microfluidic chemistry Reaction optimization of radiofluorination methods vary depending on the microfluidic systems being used but we can typically optimize 18F-labeling reaction conditions in one or two days from a single batch of [18F]fluoride. This is significantly more efficient than

• individual steps, using the Discovery mode of the Advion NanoTek® microfluidic synthesizer [16]. The first step is the preparation of the labeling reagent [18F]fluoroethyltosylate (10) via tetraethylammonium fluoride ([18F]TEAF). The second step is the reaction of the [18F]fluoroethyltosylate (10), with the

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• dyes which could be applied as FRET pair. In this case, labeling was achieved in two bioorthogonal reactions, an iEDDA and a SPAAC reaction. Furthermore, dual modification with an azido and an alkyne function enabled fluorophore/biotin labeling using a combination of SPAAC and CuAAC reaction. Efficient

• double labeling of the mRNA cap with alkyne moieties could also be achieved based on a recently reported enzymatic cascade reaction [99]. In this system a Se-propargyl-modified AdoMet analogue (SeAdoYn [100]) was prepared enzymatically from the respective methionine analogue and ATP by a methionine

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• -tetramethylpiperidine 1-oxyl), the detection of Ag(0) by X-ray photoelectron spectroscopy, the retardation of the reaction in absence of air and an 18O-labeling reaction led the authors to propose the mechanism described in Scheme 4 [23]. Because some limitations appeared with heterocycles such as quinolone, indole

Herpetopanone, a diterpene from Herpetosiphon aurantiacus discovered by isotope labeling

• Xinli Pan,
• Nicole Domin,
• Sebastian Schieferdecker,
• Hirokazu Kage,
• Martin Roth and
• Markus Nett

Beilstein J. Org. Chem. 2017, 13, 2458–2465, doi:10.3762/bjoc.13.242

• resemblance to cadinane-type sesquiterpenes from plants, but is structurally entirely unprecedented in bacteria. Based on its molecular architecture, a possible biosynthetic pathway is postulated. Keywords: genome mining; herpetopanone; Herpetosiphon; isotope labeling; terpene; Introduction Terpenoids

• labeling pattern in IPP and DMAPP (Figure 1) [8]. This feature has proven extremely useful to unravel complex cyclization cascades and carbon–carbon rearrangements in the biosynthesis of some terpenoids [9][10][11][12]. We anticipated that the resulting mass shifts could also be valuable in the field of

• been identified from H. aurantiacus 114-95T. Results and Discussion For the metabolic labeling experiment, H. aurantiacus 114-95T was grown in modified Van Niel’s yeast (VNY) medium. We had previously observed that Herpetosiphon cultures grown in this medium develop a deep orange color due to an

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

• subsequent conceptual studies [32]. For example, these were used to demonstrate the impact of non-canonical amino acids in proteins [33]. Fluoroproline-containing sequences were also applied as collagen mimics to dissect collagen-stabilizing forces [34][35]. However, the impact of fluorine labeling on

• of fluorination, as these parameters strongly impact other important biological properties, such as the potential distribution in biochemical compartments and the metabolic stability [44][45]. Considering the variety of spectroscopic applications, a labeling strategy that allows specific

• fluorine atoms in a partially fluorinated terminal alkyl group demonstrates a characteristic checkmark-shape [41]. B. Selective labeling of carboxylic acids (C-terminus in peptides) with 2,2-difluorodiazoethane yields 2,2-difluoroethyl esters [46]. C. Esters of N-acetylproline studied herein. Kinetics of

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• class particularly attractive for the development of novel sensors and fluorescent dyes [38], for instance 6-chloro-2,3-naphthaleneimide derivatives were successfully used for labeling amino acids, and for studying peptide protein interactions [39]. Even the superficial attachment to a binding domain

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• GRAS status (list of food additives that are ‘generally recognized as safe’) [9]. The present work describes the preparation of a water-soluble, solid inclusion compound of fisetin with γ-CD (see Scheme 1 for structure and atom labeling). The formation of the γ-CD·fisetin inclusion compound as a solid

• . Measurements were conducted at the steady-state of inhibition, occurring at 20 min of incubation. Structural representation of fisetin as guest (a) and γ-CD as host (b) used in the present study, depicting the herein adopted labeling for atoms and rings of fisetin. Selected FTIR bands for fisetin and its

Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• bis(triflate) (27) to give the glycosyl triflate intermediate 31, followed by glycosylation to give 30 (Scheme 7c). To distinguish between these two possibilities, an 18O-labeling study was carried out by subjecting 18O-labeled hemiacetal 28 to the glycosylation conditions. Indeed, 18O-labeled

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

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

• . Metabolic labeling experiments indicated that mycolactone exposure caused an almost complete blockage of the production of secretory and N-glycosylated proteins, which are generally processed in the ER [100]. In contrast, only minor changes in the levels of cytosolic proteins were detected. Similar results

• independent study by Demangel and co-workers, who confirmed by global proteome analysis via stable-isotope labeling with amino acids in cell culture (SILAC) [101] in T cells that mycolactone A/B is a broad-spectrum Sec61 inhibitor [102]. The mycolactone binding site on Sec61 appears to be located near a

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• to provide the 1,2-trans β-diastereomer. Only in pathway A, by direct nucleophilic displacement of the β-activated complex, does the minor α-diastereomer form. To demonstrate the potential utility of this methodology in labeling strategies, the Shoda group has also accessed fluorescent thioglycosides