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

• bioorthogonal 18F-containing building blocks The development of new 18F-based radiotracers remains an ongoing goal in the field of radiopharmacy and provides tools for specific cancer diagnostics using positron emission tomography (PET) [31][32][33]. When radiotracers are based on tumor-specific peptides

• radioactive peaks on a radio-TLC using a radio-TLC scanner (Fuji, BAS2000). [18F]Fluoride was produced using the PET cyclotron Cyclone 18/9 (IBA). [18O]H2O was irradiated with protons (18 MeV, 30 µA) exploiting the 18O(p,n)18F nuclear reaction. CAUTION! Hazard warning for organic azides: risk of explosion by

Practical synthetic strategies towards lipophilic 6-iodotetrahydroquinolines and -dihydroquinolines

• David R. Chisholm,
• Garr-Layy Zhou,
• Ehmke Pohl,
• Roy Valentine and
• Andrew Whiting

Beilstein J. Org. Chem. 2016, 12, 1851–1862, doi:10.3762/bjoc.12.174

• as supplied, and dried before use if required with appropriate drying agents or using an Innovative Technologies Inc. Solvent Purification System. Thin-layer chromatography (TLC) was conducted using Merck Millipore silica gel 60G F254 25 glassplates and/or TLC-PET foils of aluminium oxide with

Self and directed assembly: people and molecules

• Tony D. James

Beilstein J. Org. Chem. 2016, 12, 391–405, doi:10.3762/bjoc.12.42

• fluorescent photoinduced electron transfer (PET) pH sensors developed by A. P. De Silva (Figure 3) [17] in order to develop a fluorescence sensor for saccharides [18]. Thus creating a system where the neighbouring nitrogen lowered the working pH of the boronic acid and provided a fluorescence signalling

• collaborate and in particular we worked together to improve the chiral discriminating systems. In order to improve the chiral systems we designed sensors using a d-PET rather than the normal a-PET fluorescence sensing mechanism. With d-PET systems the fluorophore is the electron donor and the protonated amine

• /boronic acid moiety as the acceptor (the reverse is true for normal a-PET systems). Therefore, d-PET systems have a significant advantage over the a-PET systems at acidic pH, since background emission for these sensors is much lower. This is particularly important given that we were developing receptors

Art, auto-mechanics, and supramolecular chemistry. A merging of hobbies and career

• Eric V. Anslyn

Beilstein J. Org. Chem. 2016, 12, 362–376, doi:10.3762/bjoc.12.40

• soda indeed sparked the idea of pursuing a citrate sensor, the idea of working on sensing had been percolating in my mind for a while. A. P. De Silva was pioneering the use of PET (photoinduced electron transfer) signaling [71], Seiji Shinkai (and his post-doctoral associate Tony James) were creating

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• derivatives, bearing an arm terminated either with a hydroxy group or a fluorine atom, could be interesting candidates for diastereoisomeric intermediates and biological evaluations, especially for PET imaging experiments. Keywords: C-branched; diastereoselective; fluoroinositols; inositols; O-alkylated

• the corresponding fluoroinositol (1-fluoro-1-deoxy-scyllo-inositol) was also a good candidate to limit this aggregation. However, in vivo studies in animal models of Alzheimer disease with 1-[18F]fluoro-1-deoxy-scyllo-inositol used as radiotracer for positron emission tomography (PET) have shown that

• this compound crosses the blood brain barrier (BBB) with difficulty [32]. The same PET imaging studies using the diastereoisomeric compound of myo configuration (2-[18F]fluoro-2-deoxy-myo-inositol), did not get better results [33]. On the other hand, these radiotracers have shown interesting features

Bright molecules for sensing, computing and imaging: a tale of two once-troubled cities

• A. Prasanna de Silva

Beilstein J. Org. Chem. 2015, 11, 2774–2784, doi:10.3762/bjoc.11.298

• A. Prasanna de Silva School of Chemistry and Chemical Engineering, Queen's University, Belfast BT9 5AG, Northern Ireland 10.3762/bjoc.11.298 Abstract The circumstances in Colombo, Sri Lanka, and in Belfast, Northern Ireland, which led to a) the generalization of luminescent PET (photoinduced

• identification, nanometric mapping, animal visual perception and visual art are also outlined. Keywords: blood electrolyte analyzer; luminescent PET sensing/switching; molecular logic-based computation; photoinduced electron transfer; small molecular edge detection; Review Prologue Colombo, Sri Lanka: A civil

• from this ferment was photoinduced electron transfer (PET) [6][7], especially following the previous realization of its central role in green plant photosynthesis. It appealed to the physicochemical side of me that PET allows one to think primarily in terms of redox potentials, while atomic details

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• trifluoromethylation of aryl iodides with ClCF2CO2Me and fluoride can be utilized for clinical studies. Herein, we introduce one example of decarboxylative [18F]trifluoromethylation for positron emission tomography (PET) studies. A synthetic methodology for [18F]labelled-CF3 arenes is desired for the application of

• PET imaging. The reason is that the [18F] isotope has a longer half-life (110 min) than 13N (10 min) or 15O (2 min); however, the incorporation of [18F] must be rapid and the use of the products containing [18F] must be immediate. Many of the reported strategies have a limited scope of starting

• materials or require expensive reagents and a multistep synthesis. The [18F]trifluoromethylation performed with commercially available reagents by using [18F]fluoride demands no complex such as [18F]CF2Cu, and thus the method should contribute to efficient PET imaging [42] (Scheme 8). Synthesis of

Easy access to heterobimetallic complexes for medical imaging applications via microwave-enhanced cycloaddition

• Nicolas Desbois,
• Sandrine Pacquelet,
• Adrien Dubois,
• Clément Michelin and
• Claude P. Gros

Beilstein J. Org. Chem. 2015, 11, 2202–2208, doi:10.3762/bjoc.11.239

• easily prepared as potential MRI/PET (SPECT) bimodal contrast agents incorporating one metal (Mn, Gd) for the enhancement of contrast for MRI applications and one “cold” metal (Cu, Ga, In) for future radionuclear imaging applications. Preliminary relaxivity measurements showed that the reported complexes

• are promising contrast agents (CA) in MRI. Keywords: click chemistry; corrole; DOTA; microwave; NOTA; porphyrin; Introduction Magnetic resonance imaging (MRI), positron emission tomography (PET) or single photon emission computed tomography (SPECT) are actually the most commonly used imaging

• modalities. MRI provides high-resolution (at the submillimeter level), but is limited by its low sensitivity. Conversely, PET and SPECT imaging are more sensitive methods but they both suffer from low anatomical resolution. As one single modality is usually not sufficient to obtain all the necessary

Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• by silica column chromatography. (2′E,2E,4E)-Hex-2′-enyl 5-phenylpenta-2,4-dienoate (11a). Rf = 0.23 (20:1 pet. ether:Et2O); 1H NMR (500 MHz, CDCl3) δ 7.48–7.43 (complex m, 3H), 7.36 (app. t, J = 7.6 Hz, 2H), 7.30 (t, J = 6.9 Hz, 1H), 6.93–6.82 (complex m, 2H), 6.01 (d, J = 15.6 Hz, 1H), 5.81 (dt, J

• (neat) cm−1: 2958 (m), 2929 (m), 1706 (s), 1625 (s), 1449 (m), 1236 (s), 1172 (s), 997 (m), 689 (m); HRMS (ESI) m/z: [M + H]+ calcd for C17H21O2, 257.1536 found, 257.1529, (Δ = 2.7 ppm). (1′R,2′S,5′R,2E,4E,6E)-2′-Isopropyl-5′-methylcyclohex-1′-yl deca-2,4,6-trienoate (11f). Rf = 0.14 (40:1 pet

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• ] cycloaddition reaction [36] (Scheme 15) offered a highly efficient method with excellent regioselectivity (in case of bulky groups), with additional advantage of the C-6 fluorinated methyl substituent – promising for PET probe development. Most of the metal catalysts employed for phenanthridine synthesis are

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

• packed in a brown bottle or carton [144]. Mestdagh et al. [145] performed a comparative study of RF photodegradation in milk by using four different types of polyethylene terephthalate (PET) packages. Their results indicated that the packages provided with additional light protection and triple white

Homogeneous and heterogeneous photoredox-catalyzed hydroxymethylation of ketones and keto esters: catalyst screening, chemoselectivity and dilution effects

• Axel G. Griesbeck and
• Melissa Reckenthäler

Beilstein J. Org. Chem. 2014, 10, 1143–1150, doi:10.3762/bjoc.10.114

• appear in Table 2 for a series of ketone substrates. In order to explore the catalyst profile we tested other reaction conditions for the TiO2 catalysis, other metal-containing heterogeneous and homogeneous catalysts as well as the classical organic PET catalyst 9,10-dicyanoanthracene (DCA). The results

Organic synthesis using photoredox catalysis

• Axel G. Griesbeck

Beilstein J. Org. Chem. 2014, 10, 1097–1098, doi:10.3762/bjoc.10.107

• synthesis, the principles of photoredox chemistry serve as guidelines, i.e., photoinduced electron transfer (PET) kinetics and thermodynamics as expressed in the Rehm–Weller and Marcus equations. For catalytic versions, the photoinduced redox processes require efficient and robust photocatalysts, and in

The Ugi four-component reaction as a concise modular synthetic tool for photo-induced electron transfer donor-anthraquinone dyads

• Sarah Bay,
• Gamall Makhloufi,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 1006–1016, doi:10.3762/bjoc.10.100

• ]. This photo-induced electron transfer (PET) [30][31][32][33][34] has been investigated with donors such as porphyrines, polycyclic aromatic hydrocarbons, perylenediimides and (oligo)thiophenes [35][36], tetrathiafulvalenes [37], as well as phenothiazine and its derivatives [22][38][39][40]. The latter

• have become attractive electrophores due to their reversible and tunable oxidation potential. Interestingly quenching of the phenothiazine inherent fluorescence offers a facile evidence for the occurrence of intramolecular PET in phenothiazine-containing Do–Acc dyads [41][42]. As suitable acceptor

• Equation 2, and upon taking solvation into account with the term . Therefore, the extent of the thermodynamically favored charge separation by an intramolecular photo-induced electron transfer (PET), plausibly explaining the observed fluorescence quenching, can be easily determined and compared within the

Visible-light-induced, Ir-catalyzed reactions of N-methyl-N-((trimethylsilyl)methyl)aniline with cyclic α,β-unsaturated carbonyl compounds

• Dominik Lenhart and
• Thorsten Bach

Beilstein J. Org. Chem. 2014, 10, 890–896, doi:10.3762/bjoc.10.86

• ; Introduction The photoinduced electron transfer (PET) of an amine to an excited oxidant followed by the loss of a cationic leaving group allows accessing a broad variety of α-aminoalkyl radicals [1][2][3][4]. As first shown by Mariano et al. [5][6] and by Pandey et al. [7] a trimethylsilyl (TMS) group is a

• enones were made by Hoffmann et al., who established the use of aromatic ketones as suitable PET catalysts for these reactions [31][32][33][34][35][36][37]. In Scheme 1, the addition reaction of N,N-dimethylaniline (1) to (5R)-menthyloxyfuran-2(5H)-one (2) is shown, which proceeds to the intriguing

• as a co-solvent [39] and that the diastereoselectivity depends both on the stereogenic center at C5 and on the chirality of the menthyl (Men) backbone [40]. In more recent work [41][42], Nishibayashi et al. showed that iridium complexes can serve as efficient PET catalysts for the addition of α

Flow microreactor synthesis in organo-fluorine chemistry

• Hideki Amii,
• Aiichiro Nagaki and
• Jun-ichi Yoshida

Beilstein J. Org. Chem. 2013, 9, 2793–2802, doi:10.3762/bjoc.9.314

• , [18F]FDG is radiopharmaceutically used for positron emission tomography (PET). However, due to the short radioactivity elimination half-life of [18F] (t1/2 = 110 min), protocols for rapid and selective synthesis of [18F]-labeled compounds have been required. In addition, on-site and on-demand chemical

• production of PET agents with automation and ease of in-line purification is suitable for hospital use. To date, continuous flow microreactor technology has shown potential for synthesis of [18F]-radiolabeled molecular imaging probes such as [18F]FDG, [18F]fallypride, [18F]annexin, and so on, which were made

Flow synthesis of a versatile fructosamine mimic and quenching studies of a fructose transport probe

• Matthew B. Plutschack,
• D. Tyler McQuade,
• Giulio Valenti and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 2022–2027, doi:10.3762/bjoc.9.238

• the pancreatic islets and hepatic cells of people with diabetes, which may explain glucose insensitivity and the progression of non-alcoholic fatty liver disease [6][7]. Passive carbohydrate transporters are well-known targets for carbohydrate-based probes [8]. The positron emission tomography (PET

• Glut5-specific PET compounds which could be non-invasive tools for determining Glut5 expression in vivo and provide a means for monitoring the onset and progression of metabolic syndrome and aggressive cancers. The promising initial results obtained with NBDM prompted us to synthesize larger quantities

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• generate ionic species when stoichiometric amounts of redox reagents are used (Scheme 1) [1][2][3][4][5][6][7][8][9][10]. In contrast, radical intermediates formed by a photoinduced ET (PET) are less likely to undergo these secondary reactions, because steady-state concentrations of PET-generated redox

• hexenyl radical cyclization reactions [21], (Figure 1) [22][23][24][25][26][27][28][29][30]. For example, PET reactions of probe I with amines were observed to produce a spirocyclic ketone product while its reduction reaction induced by samarium diiodide (SmI2) gives rise to a cyclopropanol (left in

• Scheme 3) [22][24][27]. On the other hand, the same spirocyclic ketone is obtained in the 9,10-dicyanoanthracene (DCA) and biphenyl (BP) sensitized PET reaction of probe II, while reactions of this substrate with certain oxidants afford ring-expanded ketone and enone products (right in Scheme 3) [23][25

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

• relationships with regards to affinity for target and brain kinetics. Several probes discussed herein show particularly promising results and will be of immense value moving forward in the fight against AD. Keywords: Alzheimer’s disease; in vivo detection; near-infrared fluorescence probes; PET/SPECT imaging

• sensitivity and accuracy, especially in the early stages of the disease. Therefore, as Aβ plaques precede the onset of dementia and cognitive decline in AD patients, their detection by nuclear imaging techniques such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT

• resulted in a variety of radiolabeled molecular probes for in vivo PET/SPECT imaging. The scaffolds from which these newer radiolabeled probes are derived include chalcone (5) and its conformationally restricted analogues flavone (6) and aurone (7); stilbene (8) and its analogues diphenyl-1,2,4-oxadiazole

Use of 3-[¹⁸F]fluoropropanesulfonyl chloride as a prosthetic agent for the radiolabelling of amines: Investigation of precursor molecules, labelling conditions and enzymatic stability of the corresponding sulfonamides

• Reik Löser,
• Steffen Fischer,
• Achim Hiller,
• Martin Köckerling,
• Uta Funke,
• Aurélie Maisonial,
• Peter Brust and
• Jörg Steinbach

Beilstein J. Org. Chem. 2013, 9, 1002–1011, doi:10.3762/bjoc.9.115

• the application of the 18F-fluoropropansulfonyl group to the labelling of compounds relevant as imaging agents for positron emission tomography (PET), the stability of N-(4-fluorophenyl)-3-fluoropropanesulfonamide against degradation catalysed by carboxylesterase was investigated and compared to that

• modalities, positron emission tomography (PET) stands out with regards to sensitivity and quantitative image evaluation. PET is based on the application of molecules labelled with a positron-emitting radionuclide, which are termed radiotracers. Although such radionuclides are known for many elements

• , fluorine-18 can be considered as the most suitable one for PET due to its intermediate half-life of 109.8 min, its high content of β+-conversion (97%) and its rather low positron energy maximum of 640 keV [2]. From a chemical point of view, the introduction of fluorine-18 into molecules that are able to

Spectroscopic characterization of photoaccumulated radical anions: a litmus test to evaluate the efficiency of photoinduced electron transfer (PET) processes

• Maurizio Fagnoni,
• Stefano Protti,
• Davide Ravelli and
• Angelo Albini

Beilstein J. Org. Chem. 2013, 9, 800–808, doi:10.3762/bjoc.9.91

• intermediates. Keywords: aromatic nitriles; persistent radical anion; photochemical activation; photoinduced electron transfer (PET); photooxidant; reactive intermediates; Introduction Redox reactions between organic molecules have a limited scope because of the rarely matched redox potential. On the other

• reduced and an oxidized product is formed. As an example, the largely positive reduction potential of aromatic nitriles [5][8][9] and cyanophthalimides [10] in the singlet excited state or of aromatic esters in the triplet state [5][11] makes PET a common occurrence upon irradiation of such substrates in

Flow photochemistry: Old light through new windows

• Jonathan P. Knowles,
• Luke D. Elliott and
• Kevin I. Booker-Milburn

Beilstein J. Org. Chem. 2012, 8, 2025–2052, doi:10.3762/bjoc.8.229

A Wittig-olefination–Claisen-rearrangement approach to the 3-methylquinoline-4-carbaldehyde synthesis

• Mukund G. Kulkarni,
• Mayur P. Desai,
• Deekshaputra R. Birhade,
• Yunus B. Shaikh,
• Ajit N. Dhatrak and
• Ramesh Gannimani

Beilstein J. Org. Chem. 2012, 8, 1725–1729, doi:10.3762/bjoc.8.197

• reduced pressure. The crude aldehyde was purified by using silica-gel column chromatography (mobile phase 2–5% ethyl acetate in pet. ether). 4-Pentenals 3a–h were obtained in 83–89% yield. General procedure for the protection of aldehyde Aldehydes 3a–h obtained from Claisen rearrangement (15 mmol) were

Restructuring polymers via nanoconfinement and subsequent release

• Alan E. Tonelli

Beilstein J. Org. Chem. 2012, 8, 1318–1332, doi:10.3762/bjoc.8.151

• nucleant, the semi-crystalline morphology of PCL may be controlled. Of course, not only is the c-PCL nucleant necessarily nontoxic and biodegradable/bioabsorbable, it is also chemically compatible and has a “stealthy” nature. Bulk, as-received poly(ethylene terephthalate) (asr-PET) has been observed to

• reorganize both morphologically and conformationally, either by formation of a crystalline inclusion complex (IC) between guest PET and host γ-cyclodextrin (γ-CD), followed by removal of the host γ-CD and coalescence of the guest PET (c-PET), or by precipitation (p-PET) from its solution in trifluoroacetic

• acid upon gradual addition to a large excess of rapidly stirred acetone [17][52][69]. The c- and p-PETs showed very similar behaviors, but p-PET can be more easily produced in larger quantities. DSC and density observations of p-PET imply structures/morphologies and chain conformations and packing in

Improved syntheses of high hole mobility phthalocyanines: A case of steric assistance in the cyclo-oligomerisation of phthalonitriles

• Daniel J. Tate,
• Rémi Anémian,
• Richard J. Bushby,
• Suwat Nanan,
• Stuart L. Warriner and
• and Benjamin J. Whitaker

Beilstein J. Org. Chem. 2012, 8, 120–128, doi:10.3762/bjoc.8.14

• ) and the tip of the wire was bonded to the ITO surface with silver paint (RS 186-3600). The two halves were separated by a PET spacer (Goodfellow Cambridge Limited) with a thickness of 23 μm, held in position with clips and secured with epoxy resin. The thickness of the cell (d) was accurately