Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• HPLC with a C18 column using a solvent system composed of CH3CN and triethylamine phosphate (pH 3.0, see Figures S5B–S5E, Supporting Information File 1). Marfey’s method revealed the presence of 2,4-diaminobutanoic acid (Dab) and Ile in the toxin (Figures S5B and S5D). Four diastereomers are present in

• heated at 35 °C for 1 h, then 2 N aq HCl was added to quench the reaction, and then it was concentrated to dryness. The residues were dissolved in DMSO and subjected to reversed-phase HPLC (C18) using a mobile phase composed of 13% CH3CN/87% 50 mM triethylamine phosphate. Amino acid compositions of

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• as the 6’F-bc4,3-DNA. Furthermore, duplexes of a 6’F-bc4,3-modified strand paired to RNA unveiled in the MD simulations a flexible minor groove distance [37]. This flexibility is thought to play a crucial role for the fitting of the duplex into the DNA-binding channel and the phosphate-binding pocket

• of the enzyme. Furthermore, the phosphate-binding pocket requires a large distortion of the backbone angle α in order that the phosphate group of the AON can be positioned in it [50][51]. The 6’F-bc4,3-DNA containing strand also complied with this requirement according to the MD simulations [37

Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases

• Antonella Petri,
• Valeria Colonna and
• Oreste Piccolo

Beilstein J. Org. Chem. 2019, 15, 60–66, doi:10.3762/bjoc.15.6

• prochiral precursor 1-Boc-3-piperidone using immobilized ω-transaminases (TAs-IMB), isopropylamine as amine donor and pyridoxal-5’-phosphate (PLP) as cofactor is described. Compared to other methods, the present approach affords the target compound in just one step with high yield and high enantiomeric

• more sustainable method for chiral amine production [2][3][4][5]. TAs, also known as aminotransferases, are enzymes capable of transferring an amino group from an amine donor to an acceptor containing a carbonyl functionality in the presence of pyridoxal-5'-phosphate (PLP) as a cofactor and the enzymes

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• the fast growing non-pathogenic species Mycobacterium smegmatis (M. smegmatis) contains inositol phosphate-capped LAM (PILAM) [54]. In addition to lipoglycans, various free, noncovalently associated glycolipids are present in the mycobacterial cell wall, such as the mycolic acid diester trehalose 6,6

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• containing Tryptic Soy Broth (TSB) for 24 h, 48 h and 72 h at 37 °C. After each period of time, the plates were subsequently emptied and washed three times with phosphate buffered saline (PBS). The adherent cells were then fixed with cold methanol, stained with an alkaline 1% crystal violet solution for 15

• were washed with PBS (phosphate buffered saline) and 1 mL of fresh medium without antibiotics was added to each well. Suspensions of P. aeruginosa were obtained from bacterial mid-logarithmic phase cultures grown in nutrient broth adjusted to 107 CFU/mL and 1 mL were used for the inoculation of each

Synergistic approach to polycycles through Suzuki–Miyaura cross coupling and metathesis as key steps

• Sambasivarao Kotha,
• Milind Meshram and
• Chandravathi Chakkapalli

Beilstein J. Org. Chem. 2018, 14, 2468–2481, doi:10.3762/bjoc.14.223

• , compound 50 was treated with KHMDS in THF at −78 °C to produce enolate 51. Further, it was reacted with diphenyl chlorophosphate to generate vinyl phosphate 52, which was subjected to SM coupling in the presence of different 2-formylboronic acids 53 with the aid of the Pd(PPh3)4 catalyst to provide the

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• 1H NMR spectroscopy in aqueous phosphate buffer solution (pH 7.4). In the presence of 2,2’-CBP4, 1H NMR signals of P and B displayed very large upfield shifts, indicating the formation of inclusion complexes with strong binding affinities. Fluorescence titration experiments showed that P and B

• experiments of P and B with 2,2’-CBP4 in deuterated phosphate buffer (pD 7.4) were carried out to examine the host–guest complexation (Figure 1 and Figure S9 in Supporting Information File 1). From Figure 1, upon addition of the host, all the peaks of alkaloid B displayed upfield shifts and broadening

• ). To examine the fluorecence behavior and to quantitatively assess the complexation of the two alkaloids and 2,2’-CBP4, spectral titrations of P/B and 2,2’-CBP4 were performed in the phosphate buffer solution of pH 7.4 at 298 K. As can be seen from Figure 2 and Supporting Information File 1, Figure S10

Dynamic light scattering studies of the effects of salts on the diffusivity of cationic and anionic cavitands

• Anthony Wishard and
• Bruce C. Gibb

Beilstein J. Org. Chem. 2018, 14, 2212–2219, doi:10.3762/bjoc.14.195

• (Figure 3). In a previous work, our DLS studies of this host involved solutions buffered with 40 mM phosphate (pH 7.3) [14]. Under these conditions, the initially measured sizes in the absence of added salt were consistently 1.9–2.1 nm; values that match the modeling of the host. In stark contrast to this

Synthesis of new p-tert-butylcalix[4]arene-based polyammonium triazolyl amphiphiles and their binding with nucleoside phosphates

• Vladimir A. Burilov,
• Guzaliya A. Fatikhova,
• Mariya N. Dokuchaeva,
• Ramil I. Nugmanov,
• Diana A. Mironova,
• Pavel V. Dorovatovskii,
• Victor N. Khrustalev,
• Svetlana E. Solovieva and
• Igor S. Antipin

Beilstein J. Org. Chem. 2018, 14, 1980–1993, doi:10.3762/bjoc.14.173

• seen ADP more effectively embeds into the molecular cleft formed by two ammonium moieties due to a good host–guest geometric size and/or shape complementarity (Figure 4a and c). The three phosphate groups of ATP have a larger size and cannot realize a similar supramolecular motif in the complex. For

• (12b) = 2 µM, concentration (adenosine phosphate) = 2 mM, concentration (MES) = 50 mM (pH 6.5). Supramolecular binding motif of diphosphate (a) and triphosphate (b) groups of nucleotides with the protonated diethylenetriamine substituents of the calixarene (ribose and adenine fragments are omitted for

Synthesis of 9-arylalkynyl- and 9-aryl-substituted benzo[b]quinolizinium derivatives by Palladium-mediated cross-coupling reactions

• Siva Sankar Murthy Bandaru,
• Darinka Dzubiel,
• Heiko Ihmels,
• Mohebodin Karbasiyoun,
• Mohamed M. A. Mahmoud and
• Carola Schulzke

Beilstein J. Org. Chem. 2018, 14, 1871–1884, doi:10.3762/bjoc.14.161

• phosphate buffer (95 mM K+; 5% DMSO; pH 7.0); cL = 20.0 μM. Arrows indicate the development of bands with increasing DNA concentration. Inset: Plot of the absorption at long wavelength versus DNA concentration. Fluorimetric titration of 2a (A), 2b (B) and 2d (C) with ct DNA in potassium phosphate buffer (95

• 380 nm (C). Fluorimetric titration of 2a (A) and 2d (B) with 22AG in potassium phosphate buffer (95 mM K+; 5% DMSO; pH 7.0); cLigand = 20.0 μM. Arrows indicate the development of the bands with increasing DNA concentration. Inset: Plot of the relative emission intensity, I/I0 versus cDNA/cL. Lines

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

• ]arene (GC5A, Scheme 1b). Such label-free sensing strategy exhibits potential application in real-time monitoring concentrations of BPs in urine and pharmacokinetic studies. Results and Discussion The main skeleton of BPs possesses two phosphate groups which are potential binding sites and therefore GC5A

• was tested as binding receptor. GC5A was prepared according to our previous procedure [26] and the guanidinium groups installed in the upper rim are expected to form multiple salt bridge interactions (charge-assisted hydrogen bonds) with the phosphate groups of BPs (Scheme 1c) [26][29]. To execute IDA

• etidronate in (a) HEPES buffer (10 mM, pH 7.4) and (b) artificial urine at 25 °C. Error bars could not be shown if less than 0.005. The chemical structures of (a) bisphosphonates (BPs) and (b) guanidinium-modified calix[5]arene (GC5A). (c) Schematic illustration of a salt-bridge between a phosphate anion and

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• ranged from –78 °C to room temperature. The use of amines, alcohols as well as alkyl and arylthiols as nucleophiles failed to provide the corresponding products. A year later, Antilla and co-workers found lithium-binol phosphate 64 to be an efficient catalyst for the desymmetrization of meso-epoxides

• complex. Enantioselective ring-opening reaction of stilbene oxides with ArSH catalyzed by a C2-symmetric chiral bipyridyldiol–titanium complex. Asymmetric desymmetrization of meso-epoxides using BINOL-based Brønsted acid catalysts. Lithium-BINOL-phosphate-catalyzed desymmetrization of meso-epoxides with

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• -mannopyranose (3) as a 9:1 α,β-mixture in order to optimize the reaction conditions for the Mitsunobu reaction with phosphoric acid dibenzyl ester. The anomeric mannosyl phosphate derivatives 39α and 39β were obtained in 57% total yield when pyridine was used as the solvent, as depicted in Scheme 7. In THF, the

• trimethylamine in dichloromethane improved the Mitsunobu process, leading to 40α and 40β in more than 70% yield. When such optimized conditions were applied to the mannose-6-phosphate derivative 41, the desired bisphosphate 42 was obtained in 56% yield as a 40:60 α,β-anomeric mixture before work-up, and in a 53

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

• , each with 100 mW optical output power [41]. 20 min irradiation in 10 mM phosphate buffer, pH 7.4). Subsequent elimination of formic aldehyde and air oxidation transformed these intermediates into nitroxides 22c–27c. Amines 22d–27d, typical degradation products of nitroxides, could not be detected

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• reaction has been extended by using a combination of 10 mol % of Cu(OTf)2, 12 mol % of 1,10-phenanthroline, and 2 equivalents of potassium phosphate, as reported by the group of Jiang (Scheme 30) [70]. Six- to eight-membered sulfur heterocycles 67 can thus be isolated from cyclic diaryl-λ3-iodanes. More

• adding 30 mol % of dimethylethylenediamine (DMEDA) and potassium phosphate to the same pot. Symmetrical diaryl-λ3-iodanes afford the diarylated indoles 80 with yields ranging from 41% to 67%. More significantly, whereas non-symmetrical diaryl-λ3-iodanes based on electron poor/rich aryl moieties do not

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

• –S4 (Supporting Information File 1), all peptides could be successfully synthesized in high purities. First, we performed a structural analysis by diluting all peptides to a concentration of 20 μM in phosphate buffer (pH 7.0), with or without the presence of the secondary structure inducing solvent

• trifluoroethanol (TFE) [24]. As can be depicted from Figure 1, all peptides exhibited a random coil structure in phosphate buffer without TFE. In the presence of TFE, the peptides N50 and NrTP also exhibited a random coil structure, whereas N50-sC18* and NrTP-sC18* formed α-helices. This was also confirmed by the

• ; B = 0.1% TFA in acetonitrile) over 45 min and a flow rate of 6 mL·min−1. All peptides were obtained with purities >99%. CD spectroscopy All peptides were analyzed in 10 mM potassium phosphate buffer (pH 7.0) with or without the addition of TFE (1:1 dilution) using a peptide concentration of 20 µM

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• -yl triflates [47] and trap them by reaction with sydnones (Scheme 2). These strain-promoted reactions proceed quickly under very mild conditions (at room temperature, in aqueous phosphate buffer with solubilizing DMSO). In a similar manner, very reactive benzynes (didehydrobenzenes) generated either

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• , particular attention has been given to structural modifications of oligonucleotides which reduce their overall number of negative charges. One such approach is the site-specific replacement of the negatively charged phosphate diester linkage with alternative structural motifs which are positively charged at

• their oligoanionic phosphate diester backbone, severely hampers the penetration of biological barriers such as cellular membranes, thus leading to low cellular uptake. Second, unmodified ON structures are good substrates for nuclease-mediated degradation. Consequently, it is of vital importance to

• chemically modify ON structures in order to make them suitable drug candidates or chemical probes, e.g., for diagnostic purposes [6][7]. The relevance of the polyanionic phosphate diester-linked backbone to the overall function of nucleic acids has been discussed by Westheimer [8], Benner [9][10], and others

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• interactions are also augmented by a series of electrostatic and van der Waals interactions including salt bridge formation with the phosphate backbone [1]. Although, the majority of proteins recognize DNA in the major groove due, in large part, to the potential and shape complementarity, several others also

• bonding interaction between the groove floor base pairs and the amides and electrostatic stabilizing interactions between the protonated amines under physiological pH and negatively charged phosphate backbone as reported by NMR and crystallographic studies [32][33][34][35][36]. These molecules were shown

• show excellent antileukemic activity and are found to be significantly less myelotoxic than TAM against murine and human hematopoietic progenitor cells [43]. The positively charged basic amidino side chain, responsible for electrostatic interaction with negatively charged DNA phosphate backbone, was

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• )diisopropylaminophosphoramidite with a partially-protected guanosine derivative to the corresponding phosphite triester was also effected (Scheme 12). Phosphate coupling using nucleoside phosphoromorpholidates is well established [51] but the reaction times are typically in the order of days. Recent developments in this field

• ) and adenosine diphosphate ribose (ADPR) was also described. Subsequently, this methodology was applied to the preparation of a library of six ADPR carbonate derivatives in 23–68% yields (e.g., Scheme 14) and tested as sirtuin inhibitors [54]. The efficiency of phosphate coupling under mechanochemical

• of the monoester and phosphate coupling to AMP-morpholidate to be effected in one pot using LAG. Both 3′,5′- and 5′,5′- internucleoside linkages were prepared using this route. Mechanochemical transformations of nucleosides and related materials involving non-covalent bonds Dissociative processes for

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• characterized in 1966 by Wall et al. [96][97]. The main mechanism of action involves binding to the reversible complex of topoisomerase I (topo I) and the 3′-phosphate group of the DNA backbone through hydrogen bonding, resulting in accumulation of a persistent ternary complex (the cleavable complex). This

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

• the next one are cleaved by a variety of enzymes [1]. The phosphodiester bonds of DNA are hydrolyzed, depending on the enzyme, either to a 3´- or 5´-phosphate, whereas the bonds in RNA, with few exceptions (above all RNase H-catalyzed cleavages) undergo transesterification to a 2´,3´-cyclic phosphate

• protein nucleases and ribozymes a subject of intensive mechanistic studies. pH-Rate dependency, X-ray structures, amino acid/nucleotide substitution experiments and the effect of thiosubstitution of phosphate oxygens on the binding of metal ion cofactors have given invaluable information about the

• 13.5 for an apical group [22]. For a cyclic phosphorane derived from ethylene phosphate, the first pKa value is 7.9 and the second 14.3, both values referring to an equatorial hydroxy ligand [23]. Accordingly, both neutral phosphorane and its monoanion are present in significant amount at physiological

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• and supramolecular complexes [10][11][12][13][14][15][16][17][18][19][20][21][22]. Nucleic acids are composed of a monomeric nucleoside unit that features an aromatic nitrogenous moiety (a nucleobase) connected to a pentose sugar, which in turn is attached to a phosphate group (Figure 1) [7]. The

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

• medium for the indicated incubation time. Cells were washed two times with phosphate buffered saline (PBS) and fixed by 4% paraformaldehyde for 20 min at 37 °C. After three times washing with PBS, nuclei were stained by 4′,6-diamidine-2-phenylindole dihydrochloride (DAPI, 0.2 µg/mL, dissolved in PBS

An uracil-linked hydroxyflavone probe for the recognition of ATP

• Márton Bojtár,
• Péter Zoltán Janzsó-Berend,
• Dávid Mester,
• Dóra Hessz,
• Mihály Kállay,
• Miklós Kubinyi and
• István Bitter

Beilstein J. Org. Chem. 2018, 14, 747–755, doi:10.3762/bjoc.14.63

• recognition sites [16][18][19][33], or Zn-dipicolylamine complexes [21][23][24] attracting the negatively charged phosphate units of ATP and by π-stacking between the fluorophores of the sensors and the adenine moiety of ATP [29]. In aqueous solutions at physiological pH, the tetra-charged anionic ATP

• consists of a hydrophilic (phosphate and ribose) and a more hydrophobic part (adenine). The former ensures a good solubility of ATP in water and generates an electrostatic field around it while the latter is required for associations with similar planar hydrophobic molecules involved in the biochemical

• different concentrations are shown in Figure 3. Upon addition of ATP, a new band appears at 440 nm in the excitation spectra. This feature can be attributed to the specific intermolecular proton transfer from the hydroxy group of the flavone to the phosphate moiety of the ATP [34]. The fluorescence