Design and biological characterization of novel cell-penetrating peptides preferentially targeting cell nuclei and subnuclear regions

• Anja Gronewold,
• Mareike Horn and
• Ines Neundorf

Beilstein J. Org. Chem. 2018, 14, 1378–1388, doi:10.3762/bjoc.14.116

• (Marktredwitz, Germany). Other chemicals and consumables including 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxide hexafluorophosphate (HATU), N,N-diisopropylethylamine (DIPEA), acetonitrile (ACN), and trifluoroacetic acid (TFA), dimethylformamide (DMF), N-methylpyrrolidine (NMP

Development of novel cyclic NGR peptide–daunomycin conjugates with dual targeting property

• Andrea Angelo Pierluigi Tripodi,
• Szilárd Tóth,
• Kata Nóra Enyedi,
• Gitta Schlosser,
• Gergely Szakács and
• Gábor Mező

Beilstein J. Org. Chem. 2018, 14, 911–918, doi:10.3762/bjoc.14.78

• . The lyophilized compound was then purified by RP-HPLC prior to the cyclization. Cyclization Prior to the head-to-side chain cyclization a salt exchange needs to be performed using 10 equiv of pyridinium hydrochloride in 5 mL MeOH. After 20 min volatiles were removed under reduced pressure, the

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

• small heterocycles, such as pyridine, can increase the rate of the reaction [60]. Most probably, this effect was organocatalytic in nature, being caused by a pyridinium species that forms in the reaction medium, an effect known from the acceleration of DCC-induced acylation reactions with

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• advantages of solution chemistry and solid-phase methods. Thus, solid-supported acyl chloride or pyridinium tosylate as the activator of nucleoside-3'-O-H-phosphonates/phosphoramidites, and polystyrene-bound trimethylammonium periodate as oxidation reagent have been demonstrated to be superior for dimer and

Transition-metal-free [3 + 3] annulation of indol-2-ylmethyl carbanions to nitroarenes. A novel synthesis of indolo[3,2-b]quinolines (quindolines)

• Michał Nowacki and
• Krzysztof Wojciechowski

Beilstein J. Org. Chem. 2018, 14, 194–202, doi:10.3762/bjoc.14.14

• ]. Several methods use prerequisite quinoline derivatives for the construction of the pyrrole ring of quindoline. 2-(2-Aminophenyl)-3-bromoquinoline cyclized to quindoline by reacting with pyridinium hydrochloride (d) [14]. Insertion of nitrene generated from 2-(2-nitrophenyl)quinoline by triethylphosphite

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C–O bond instead of the N–O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening

• -opened product at a yield of 38% (Table 1, entry 7) while using camphorsulfonic acid (CSA) increased the yield to 50% but took 46 hours to go to completion (Table 1, entry 8). The organic acid pyridinium p-toluenesulfonate (PPTS) produced the highest yield of ring-opened product with a 61% yield (Table 1

• examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C–O bond instead of the N–O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening reactions. The scope

The photodecarboxylative addition of carboxylates to phthalimides as a key-step in the synthesis of biologically active 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones

• Ommid Anamimoghadam,
• Saira Mumtaz,
• Anke Nietsch,
• Gaetano Saya,
• Cherie A. Motti,
• Jun Wang,
• Peter C. Junk,
• Ashfaq Mahmood Qureshi and
• Michael Oelgemöller

Beilstein J. Org. Chem. 2017, 13, 2833–2841, doi:10.3762/bjoc.13.275

• 8a–y, possibly via an acylaminium cation intermediate (Scheme 9) [60]. The change in stability may be caused by a stabilizing ionic–π interaction for the Z-isomer during isomerization [61]. A similar thermal isomerization towards the more stable isomer induced by catalytic amounts of pyridinium p

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• , oxidation of the secondary alcohol with pyridinium dichromate into the corresponding cyclopentanone derivative and subsequent olefination using CBr3F gave the monofluoroalkene 96 with a modest selectivity towards the (Z)-alkene. A Negishi coupling then gave alkene 98. Stereoselective reductive amination

Electron-deficient pyridinium salts/thiourea cooperative catalyzed O-glycosylation via activation of O-glycosyl trichloroacetimidate donors

• Mukta Shaw,
• Yogesh Kumar,
• Rima Thakur and
• Amit Kumar

Beilstein J. Org. Chem. 2017, 13, 2385–2395, doi:10.3762/bjoc.13.236

• trichloroacetimidate donors using a synergistic catalytic system of electron-deficient pyridinium salts/aryl thiourea derivatives at room temperature is demonstrated. The acidity of the adduct formed by the 1,2-addition of alcohol to the electron-deficient pyridinium salt is increased in the presence of an aryl

• , the optimized method is also utilized for the regioselective O-glycosylation by using a partially protected acceptor. Keywords: cooperative catalysis; electron-deficient pyridinium salts; O-glycoside; regioselectivity; thiourea; Introduction The glycosidic linkage is the principal bond present in a

• activation at room temperature [32][33][34][35][36]. It is known from the literature that pyridinium salts exhibit pKa values of about 5.2 [37]. Of late, Berkessel et al. disclosed an elegant method, where different electron deficient pyridinium salts (expected pKa values less than 5) were used as a catalyst

Chiral phase-transfer catalysis in the asymmetric α-heterofunctionalization of prochiral nucleophiles

• Johannes Schörgenhumer,
• Maximilian Tiffner and
• Mario Waser

Beilstein J. Org. Chem. 2017, 13, 1753–1769, doi:10.3762/bjoc.13.170

• anions can control Pd-catalysed α-fluorinations [84]). Very interestingly, however, the authors clearly proved that the nature of the F-transfer reagent is crucial to obtain high selectivities. While NFSI or SelectfluorTM did not give reasonable enantioselectivities [81], the pyridinium salt 6 turned out

Block copolymers from ionic liquids for the preparation of thin carbonaceous shells

• Sadaf Hanif,
• Bernd Oschmann,
• Dmitri Spetter,
• Muhammad Nawaz Tahir,
• Wolfgang Tremel and
• Rudolf Zentel

Beilstein J. Org. Chem. 2017, 13, 1693–1701, doi:10.3762/bjoc.13.163

• organic asymmetric cations, like imidazolium, pyridinium or alkylammonium and inorganic anions, such as halides, mineral acid anions, or polyatomic inorganic anions (PF6−, BF4−) [3]. Because of the steric hindrance, they are not able to build a strong lattice like inorganic salts. Therefore, not much

Oxidative dehydrogenation of C–C and C–N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

• Santanu Hati,
• Ulrike Holzgrabe and
• Subhabrata Sen

Beilstein J. Org. Chem. 2017, 13, 1670–1692, doi:10.3762/bjoc.13.162

• MnO2. Selenium dioxide and potassium dichromate-mediated oxidative dehydrogenation of tetrahydro-β-carbolines [65][66]. Synthesis of substituted benzazoles in the presence of barium permanganate. Oxidative dehydrogenation with phenanthroline-based catalysts. PPTS = pyridinium p-toluenesulfonic acid

Synthesis and metal binding properties of N-alkylcarboxyspiropyrans

• Alexis Perry and
• Christina J. Kousseff

Beilstein J. Org. Chem. 2017, 13, 1542–1550, doi:10.3762/bjoc.13.154

• previously reported [28]. Presumably, this reaction proceeds via azomethine ylid 6 (Scheme 3); analogous indolium ylids have been used synthetically in 1,3-dipolar cycloadditions [29] and mechanistic studies have been published on the related decarboxylation of pyridinium 2-carboxylates [30]. Fortunately, α

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• linker by 5 mmol L−1 K2CO3 in a 3:43:10 mixture of DCM, dioxane and MeOH (30 min), followed by neutralization with pyridinium chloride, left the 5´-O-DMTr group, 2-chlorophenyl phosphate protections and base moiety protections untouched. Silica gel chromatographic purification and conventional

Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

• Josef Jansa,
• Ramona Schmidt,
• Ashenafi Damtew Mamuye,
• Laura Castoldi,
• Alexander Roller,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2017, 13, 895–902, doi:10.3762/bjoc.13.90

• the pyridine nitrogens of the azine ring attached to pyrazole N-1 are somewhat smaller than those of the corresponding pyridine N-atoms in systems attached to pyrazole C-3, C-5 (or C-4), whereas the C-3-pyridine nitrogen atom in many cases was the most deshielded one. The pyridinium-type nitrogen (N-6

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

• treating asthma and post-stroke patients [16]. 1,2,4-Triazolo[1,5-a]pyridines show antifungal [17], antitumor [18], and cytotoxic [19] activities. Both types of heterocyclic cores are readily available from N-aminopyridium salts and related pyridinium-N-imines via 1,3-cycloaddition reaction [20] or

• 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

• different positions of pyridinium cations we carried out DFT calculations [31] at the M06-2X 6-31+G(d,p) [32] level of theory with SMD [33] solvation (Figure 1, see also Supporting Information File 1). As expected, in all cases the NH2 group is the most acidic. The NH2 group is usually ≈12–13 pKa units more

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• ). The reaction of 5 with ethanethiol in the presence of hydrochloric acid followed by selective protection of the 4,5-diol with 2,2-dimethoxypropane using pyridinium p-toluenesulfonate as the promoter gave the 4,5-O-isopropylidene derivative 6 in 71% yield over two steps [40]. Treatment of diol 6 with

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• in situ by deprotonation with KHMDS of its pyridinium ion precursor 79 in refluxing toluene (method B). With method B, malononitriles are reduced to mononitriles with comparable yields to that achieved with photoactivated 78 (73k,m,n). No allylic bond cleavage is observed and alkene moieties are

Interactions between photoacidic 3-hydroxynaphtho[1,2-b]quinolizinium and cucurbit[7]uril: Influence on acidity in the ground and excited state

• Jonas Becher,
• Daria V. Berdnikova,
• Darinka Dzubiel,
• Heiko Ihmels and
• Phil M. Pithan

Beilstein J. Org. Chem. 2017, 13, 203–212, doi:10.3762/bjoc.13.23

• )pyridine (3) [43] with 2-methoxy-6-bromomethylnaphthalene (4) [44] gave the corresponding (naphthylmethyl)pyridinium bromide 5 in 62% yield. Subsequent treatment of this intermediate with aq HBr (48%) led to acid-catalyzed cyclization and elimination of water, as well as to demethylation of the ether group

• ]. Notably, the chromophore of the oxyanion-substituted quinolizinium derivative 2cB resembles the well-established solvatochromic pyridinium-N-phenolate betaine dyes that are employed as polarity probes [53]. Correspondingly, the derivative 2cB shows a similar positive solvatochromism, i.e., a blue shift of

• , Flawil, CH); uncorrected. Synthesis 2-(1,3-Dioxolan-2-yl)-1-[(6-methoxynaphth-2-yl)methyl]pyridinium bromide (5). Under argon-gas atmosphere, a solution of 2-(1,3-dioxolan-2-yl)pyridine (3) [43] (1.83 g, 12.1 mmol) and 6-methoxy-2-bromomethylnaphthalene (4) [44] (3.05 g, 12.1 mmol) in DMSO (90 mL) was

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

• . In D1 and D2, the pyridinium part is connected to the rest of the dye by its 4-position, in D3 and D4 via its 2-position. The latter connectivity has a larger stabilizing influence on the DNA2a double strands. The fluorescence quantum yields of dsDNA2a are all higher than the corresponding ones of

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• attributed to their ability to form a hydrogen bond with the oxygen of epoxide. In 2015 Shirakawa and Maruoka demonstrated that ammonium salts L5 and L6 could serve as effective catalysts for isoquinolinium and pyridinium salt Mannich reactions (Scheme 7) [50]. Catalysts L5 and L6 were selected due to their

• -workers reported the use of N-alkylated 3,5-di(carbomethoxy)pyridinium ions L13 to catalyze the reaction between 1-chloroisochroman and silyl ketene acetals (Scheme 10A). Catalyst L13 with R3 = C6F5 was found to be particularly active, and was found to efficiently form the product at 2 mol % loading

• propose that catalysts L13 could act not only through Coulombic interactions, but also as hydrogen bond donors. While various factors including Coulombic interactions between the pyridinium (or ammonium) salt and the chloride undoubtedly play an important role in promoting substrate ionization and

Sydnone C-4 heteroarylation with an indolizine ring via Chichibabin indolizine synthesis

• Florin Albota,
• Mino R. Caira,
• Constantin Draghici,
• Florea Dumitrascu and
• Denisa E. Dumitrescu

Beilstein J. Org. Chem. 2016, 12, 2503–2510, doi:10.3762/bjoc.12.245

• Pharmacy, University Ovidius, Aleea Universitatii 1, Constantza, Romania 10.3762/bjoc.12.245 Abstract The synthesis of sydnones heteroarylated at C-4 with an indolizine was achieved by Chichibabin (Tschitschibabin) indolizine synthesis starting from the corresponding sydnone-N-pyridinium bromides. The

• ; Chichibabin synthesis; indolizine; pyridinium N-ylide; sydnone; Introduction In recent decades, interest in the syntheses of biheteroaryls has been focused on the creation of new hetaryl–hetaryl C(sp2)–C(sp2) bonds, in particular through cross-coupling reactions. These reactions are catalyzed by palladium or

• pyridinium salts used in the indolizine Chichibabin synthesis. Results and Discussion In order to obtain the compounds 4 containing an indolizine ring attached directly to the C-4 carbon atom of a sydnone ring (i.e., indolizination of sydnones at C-4), the Chichibabin indolizine synthesis was employed. The

A new protocol for the synthesis of 4,7,12,15-tetrachloro[2.2]paracyclophane

• Donghui Pan,
• Yanbin Wang and
• Guomin Xiao

Beilstein J. Org. Chem. 2016, 12, 2443–2449, doi:10.3762/bjoc.12.237

• in the bromination process [10][11][12]. In addition, the release of corrosive HBr as a byproduct and the use of organic solvents make this protocol less environmentally friendly [13]. The use of other brominating agents, such as N-bromosuccinimide (NBS) and pyridinium tribromides, also has the

Elongated and substituted triazine-based tricarboxylic acid linkers for MOFs

• Arne Klinkebiel,
• Ole Beyer,
• Barbara Malawko and
• Ulrich Lüning

Beilstein J. Org. Chem. 2016, 12, 2267–2273, doi:10.3762/bjoc.12.219

• improve the yield, a methoxy cleaving procedure which has been found to be effective in other demanding demethylations [24] was used. In liquid pyridinium chloride (which melts at 144 °C), apparently all intermediates were sufficiently soluble and consequently all four methoxy groups of 16c could be

• from the methoxy-substituted triester 19c. As successfully applied for 16c, molten pyridinium chloride was used as the cleaving reagent and all four methoxy groups of 19c could be cleaved leading to the hydroxy-substituted triacid 20e in 62% yield. All three triacids 20a, b and e precipitate from water

• , 60 °C, quant., d) pyridinium hydrochloride, 12 h, 200 °C, 17e: 52%. Triple Suzuki coupling between tribromotriazines 3 and boronate 18. Conditions: a) 19a: Pd(PPh3)4, K3PO4, dioxane/H2O, 2 d, 120 °C, 24%; 19b: Pd(dppf)Cl2, K3PO4, dioxane/H2O, 3 d, 120 °C, 16%; 19c: Pd(PPh3)4, K3PO4, dioxane/H2O, 2 d