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

α-Acetoxyarone synthesis via iodine-catalyzed and tert-butyl hydroperoxide-mediateded self-intermolecular oxidative coupling of aryl ketones

• Liquan Tan,
• Cui Chen and
• Weibing Liu

Beilstein J. Org. Chem. 2017, 13, 1079–1084, doi:10.3762/bjoc.13.107

• radical pathways. Multiple radical intermediates were generated in situ and the overall process involved several different reactions, which proceeded self-sequentially in a single reactor. A labeling experiment using 18O-labeled H2O confirmed that the oxygen in the product was derived from TBHP, not from

Glyco-gold nanoparticles: synthesis and applications

• Federica Compostella,
• Olimpia Pitirollo,
• Alessandro Silvestri and
• Laura Polito

Beilstein J. Org. Chem. 2017, 13, 1008–1021, doi:10.3762/bjoc.13.100

• embedded on PEGylated-gold nanoparticles and the sugar moiety displayed on the outer shell of the nanosystem is available for interaction with lectin. In 2016, Sakurai and co-workers [81] combined the multiple display of the carbohydrate moiety on AuNPs with the photoaffinity labeling (PAL), to concentrate

• coating. When galactoside-coated AuNPs interact with lectin, AuNPs aggregates, inducing a plasmonic band shift. Reprinted with permission from [25]. Copyright 2015 American Chemical Society. A photoaffinity labeling (PAL) approach based on glyco-gold nanoparticles is able to recognize and isolate only 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

• known for the formation and coexistence of lateral disordered (ld) and ordered (lo) domains. The domain structure was visualized by labeling the membrane with the ld marker 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (ammonium salt) (N-Rh-DOPE) and recording z-stacks

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• mechanism of their action and their fate inside living cells. The fluorescent labeling of CDs enables their tracking and visualization in biological media and provides useful information about their cell-membrane-penetration ability [2][3]. Besides, fluorophore-appended CDs have been extensively studied and

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

• structurally related natural products to date. In this study, inspired by our previous genomic analysis, incorporation of 13C- and 2H-labeled precursors into butyrolactol A was investigated. Based on the labeling pattern and sequencing analytical data, we confirmed that the tert-butyl group is derived from

• -labeling result, this labeling pattern suggested that the carbons from C-1 to C-8 are derived from hydroxymalonyl-ACP. This conclusion is supported by the sequencing analysis of the gene cluster for butyrolactol biosynthesis (Figure 5, Table 2). Four genes coding homologues of enzymes involved in

• experiments of isotope-labeled precursors in combination with the bioinformatics analysis of its biosynthetic genes. The overall result of labeling experiments is summarized in Figure 8. The tert-butyl group was shown to be derived from the C-methylated isopropyl group of valine. This is the first study that

Solid-phase enrichment and analysis of electrophilic natural products

• Frank Wesche,
• Yue He and
• Helge B. Bode

Beilstein J. Org. Chem. 2017, 13, 405–409, doi:10.3762/bjoc.13.43

• combination with labeling experiments even the nature of the parent natural product could be revealed. Moreover, a possible scale-up of this procedure should enable the preparative purification of yet unidentified compounds as well as the structural confirmation of the identified structures. This approach can

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

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

• limited to, the synthesis of isotopically-labeled precursors and the analysis of the resulting labeling patterns, characterization by assays in vitro of wild type and mutant recombinant enzymes in the presence of synthetic substrates, and genetic engineering of model systems coupled with analysis of

• labeling at C-2, C-4, and C-10 of the macrolide ring. This result was consistent with incorporation of (2S)-methylmalonyl-CoA during the second, fifth, and sixth chain extension cycles, with inversion of configuration at the C-2 center as found for fatty acid biosynthesis (vide infra) [24]. However

• the stereochemistry of the less common extender units, labeling studies indicate that the (2S) isomer of ethylmalonyl-CoA is also used [39], which correlates with it originating predominantly from the reductive carboxylation of crotonyl-CoA [40]. Several extender units including aminomalonyl-ACP [41

Correction: Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2017, 13, 301–302, doi:10.3762/bjoc.13.32

• : building blocks; coalescence; dynamic NMR; labeling; Staudinger ligation; In the original article an incorrect caption for Figure 1 was given. The assignment of the solvents to the capital letters was not correct. The correct caption of Figure 1 is: 1H NMR spectra of compound 3a measured in five different

A postsynthetically 2’-“clickable” uridine with arabino configuration and its application for fluorescent labeling and imaging of DNA

• Heidi-Kristin Walter,
• Bettina Olshausen,
• Ute Schepers and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2017, 13, 127–137, doi:10.3762/bjoc.13.16

Versatile synthesis of end-reactive polyrotaxanes applicable to fabrication of supramolecular biomaterials

• Atsushi Tamura,
• Asato Tonegawa,
• Yoshinori Arisaka and
• Nobuhiko Yui

Beilstein J. Org. Chem. 2016, 12, 2883–2892, doi:10.3762/bjoc.12.287

• -catalyzed click reactions are performed. Additionally, fluorescence labeling of the PRX and intracellular fluorescence imaging were performed as an example application. Results and Discussion Synthesis of azide-terminated PRXs using bis(2-amino-3-phenylpropyl) poly(ethylene glycol) and 4-substituted benzoic

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• amide probes UA1–3 and the α,β-unsaturated ketone UK1 only resulted in very weak or no labeling, all three α-chloroacetamide probes CA1–3 gave a strong fluorescent signal in the gel (Figure 3A). In order to investigate the selectivity of the probes, we constructed a PqsD C112A mutant, where the active

• site cysteine was replaced by alanine. The purified mutant PqsD C112A exhibited only low background labeling for some probes but not comparable to labelling of the wild type protein by CA1–3, indicating that the probes were selectively targeting the active site (Figure 3A). Concentration series with a

• , variations in the probe structure had little impact on labeling intensity and specificity. Although each α-chloroacetamide probe had one closely related α,β-unsaturated acetamide counterpart, only the reactive group but not the structure of the probe or its side groups determined active-site labeling. These

Benzothiadiazole oligoene fatty acids: fluorescent dyes with large Stokes shifts

• Lukas J. Patalag and
• Daniel B. Werz

Beilstein J. Org. Chem. 2016, 12, 2739–2747, doi:10.3762/bjoc.12.270

• , but spectroscopically different fluorescent probes we believe that these fatty acids might find interest as useful candidates to study the sensitive hydrophobic area of membranes in terms of domain formation or as labeling agents in general. Experimental General. All solvents for column chromatography

Synthesis, dynamic NMR characterization and XRD studies of novel N,N’-substituted piperazines for bioorthogonal labeling

• Constantin Mamat,
• Marc Pretze,
• Matthew Gott and
• Martin Köckerling

Beilstein J. Org. Chem. 2016, 12, 2478–2489, doi:10.3762/bjoc.12.242

• (1)°, V = 1325.74(4) Å3, Z = 4, Dobs = 1.304 g/cm3) were obtained from a saturated ethyl acetate solution. The rotational conformation of these compounds was also verified by XRD. As proof of concept for future labeling purposes, both nitropiperazines were reacted with [18F]F–. To test the

• applicability of these compounds as possible 18F-building blocks, two biomolecules were modified and chosen for conjugation either using the Huisgen-click reaction or the traceless Staudinger ligation. Keywords: building blocks; coalescence; dynamic NMR; labeling; Staudinger ligation; Introduction The

• development of new building blocks for specific and bioorthogonal labeling of biologically active compounds is of high importance. Depending on their size and composition, building blocks can influence (bio-)chemical parameters such as the lipophilicity (log P) affecting the solubility and the biological

Enantioconvergent catalysis

• Justin T. Mohr,
• Jared T. Moore and
• Brian M. Stoltz

Beilstein J. Org. Chem. 2016, 12, 2038–2045, doi:10.3762/bjoc.12.192

• . Deuterium labeling experiments have shown that the hydrogenation reaction occurs only on the chiral keto tautomer, and therefore the catalyst selects one enantiomer of the substrate when the reduction takes place. Enantioconvergent methods are not limited to carbon stereocenters. An exceptional example of

• ]. The observed product arises from hydrolysis of each enantiomer of epoxide at the S-configured carbon atom. Isotopic labeling studies with 18OH2 not only confirmed this mechanistic hypothesis, but also facilitated kinetic studies to determine relative rate constants for each of the four reaction