Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• reactive intermediate capable of transferring a phosphate group to ATP. The Guareschi “1897 reaction” shows a basically different strategy to generate reductive power, associated to aromatization of a prearomatic substrate. The chemiosmotic generation of energy is as universal as the genetic code, and the

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• GmbH (Ulm, Germany). Oligonucleotides were dissolved in K-phosphate buffer, and the solution was heated to 95 °C for 5 min and then cooled slowly to room temperature within 4 h. K-phosphate buffer: 25 mM K2HPO4, 60 mM KCl; adjusted with 50 mM KH2PO4, 60 mM KCl to pH 7.0; BPE (biphosphate EDTA) buffer

• : Plots of the relative fluorescence intensity versus the temperature of the solution. Photometric titration of 5a (A) and 5d (B) (cLigand = 20 μM) with ct DNA (1) in BPE buffer (cNa+ = 16 mM, pH 7.0, with 5% v/v DMSO) and with 22AG (2) in K-phosphate buffer (cK+ = 110 mM, pH 7.0, with 5% v/v DMSO). The

• arrows indicate the changes of the absorption bands upon addition of DNA. Inset: Plot of the ligand absorption versus cDNA (in base pairs). Fluorimetric titration of 5a (A) and 5d (B, cLigand = 20 μM) with ct DNA (1) in BPE buffer (cNa+ = 16 mM, pH 7.0, with 5% v/v DMSO) and with 22AG (2) in K-phosphate

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• apoptosis [1][2][3][4][5][6][7]. Due to its involvement in a wide range of cellular processes, significant efforts have been made in the last two decades targeting sphingosine analogues signalling as a therapeutic strategy. For instance, FTY720-P (3), the phosphate of FTY720 (2, fingolimod), proved to be a

• very good agonist for the S1P1 receptor (Figure 1). Sphingosine 1-phosphate (S1P, 4), in turn, performed critical regulator functions in many physiological and pathological treatments, such as Alzheimer’s disease [8][9], cancer [10][11][12][13], multiple sclerosis [14], and inflammation [15]. Due to

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• oligonucleotides that have been explored for gene silencing. Keywords: antisense; chemically modified oligonucleotides; crystallography; siRNA; structure; Introduction The natural nucleic acids sugar-phosphate backbone comes in two flavors, 2'-deoxyribose in DNA and ribose in RNA. However, this relative

• phosphorothioate Rp-stereoisomer (Rp-PS, i.e., phosphate with one of the non-bridging oxygens replaced by sulfur) in bacterial genomes, where it may serve a protective role against nucleases [4] and its loss results in genomic instability [5]. There are over a hundred known base modifications in RNA and the Rp-PS

• therapeutic tool [15]. The chemical make-up of RNA, i.e., the ribose-phosphate backbone, has inspired countless strategies to chemically modify either the sugar [12][41][42][43][44], or the phosphate (e.g., amide-RNA [45]), or both [46][47]. In addition, the ribose has been replaced with alternative sugar

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• (phosphate-buffered saline, PBS) conditions (Figure 4A). Additionally, we confirmed LNP uptake by the monocyte-derived macrophages (MDMs) using fluorescent microscopy (Figure 4B). We found that all LNPs containing the Cy5 oligonucleotide were observable under the microscope (Figure 4B) and that all

Synthesis of bis(aryloxy)fluoromethanes using a heterodihalocarbene strategy

• Carl Recsei and
• Yaniv Barda

Beilstein J. Org. Chem. 2021, 17, 813–818, doi:10.3762/bjoc.17.70

• strategy, we were delighted to observe that the desired compound, 4, was produced as the major product, in 39% yield (72% yield based on recovered starting material) when 6 was reacted with dibromofluoromethane in the presence of excess potassium phosphate in acetonitrile (Scheme 4). Smaller amounts of the

Synthetic reactions driven by electron-donor–acceptor (EDA) complexes

• Zhonglie Yang,
• Yutong Liu,
• Kun Cao,
• Xiaobin Zhang,
• Hezhong Jiang and
• Jiahong Li

Beilstein J. Org. Chem. 2021, 17, 771–799, doi:10.3762/bjoc.17.67

• [32] found a bifunctional group reaction of perfluoroalkylation and β-alkenylation by a perfluoroalkyl radical. Perfluoroalkylation product 93 was synthesized by utilizing (E)-3-methyl-1-phenylhept-1,6-dien-3-ol (92) and perfluorobutyl iodide (28) as substrates and potassium phosphate and DABCO as

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• Yongdong Su Maitsetseg Bayarjargal Tracy K. Hale Vyacheslav V. Filichev School of Fundamental Sciences, Massey University, Private Bag 11-222, 4442 Palmerston North, New Zealand Maurice Wilkins Centre for Molecular Biodiscovery, Auckland 1142, New Zealand 10.3762/bjoc.17.65 Abstract Two phosphate

• phosphate backbone of DNA and RNA, especially charge neutral modifications, have gained attention in recent years because such modifications not only improve the nuclease resistance of ONs but also enhance their affinity towards complementary DNA/RNA/dsDNA and improve cell uptake. The lack of a negatively

• reversed [32]. As a charge-neutral phosphate mimic, the methylphosphonate linkage (PMe) has been introduced into the DNA backbone to improve stability of ONs towards enzymic digestion as well as DNA duplex and triplex binding affinity [33]. However, the poor aqueous solubility [34], reduced binding

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• a Tm analysis accessory. Equimolecular amounts of the target ssRNAs or ssDNAs and the oligonucleotides were dissolved in 10 mM sodium phosphate buffer (pH 7.2) containing 100 mM NaCl to achieve a final strand concentration of 4 µM. The samples were annealed by heating at 95 °C followed by slow

• , and path length in centimeters, respectively. Structures of 2',4'-BNA/LNA analogs. The CD spectra of the ON7/ssRNA, ON2/ssRNA, ON7/ssDNA, and ON2/ssDNA duplexes. Conditions: 10 mM sodium phosphate buffer (pH 7.2), 100 mM NaCl, 4 µM each oligonucleotide. Sequences of the complementary ssRNA and ssDNA

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• -volatile precursor that is stored in garlic and related plants and only degraded into sulfur volatiles upon wounding by the pyridoxal phosphate (PLP) dependent alliinase (Scheme 1B) [7]. This initial enzyme-catalyzed reaction yields one equivalent of allylsulfenic acid (10), pyruvic acid (11), and ammonia

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• with thiobenzamide (2a) did not proceed at all and only the formation of isoindigo 9a was observed. However, a very easy synthesis of diethyl (2-oxoindolin-3-yl)phosphate (1g) from isatin has recently appeared [42] which encouraged us to submit this reagent to the Eschenmoser reaction. Unfortunately

• , this reagent reacts with the parent thiobenzamide (2a) very slowly even after heating to 80 °C. A maximum (chromatographic) yield 38% of 5aa was achieved after 32 h when a double molar excess of phosphate 1g was used. A further increase in the excess of 1g had no positive effect on the yield of 5aa

• . This result is in accordance with the relatively low nucleofugality of diethyl phosphate which is roughly quantified by the pKa = 1.39 of its conjugated acid [43]. We have also examined an addition of 20% of tetrabutylammonium bromide as a nucleophilic catalyst which could transform the phosphate 1g in

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• are derivatives of the new antimalarial drug fosmidomycin and inhibited the 1-deoxy-ᴅ-xylulose 5-phosphate reductoisomerase. The phosphonodepsipeptides 194 were synthesized as prodrugs with an increased activity after oral administration due to a chemical modification of the phosphonate moiety. For

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• the action of glutamate 5-kinase (enzyme proB, Figure 9A). The resulting intermediate undergoes reduction into glutamate semialdehyde via the action of the γ-glutamyl phosphate reductase proA. The semialdehyde then undergoes spontaneous cyclization to form 1-pyrroline-5-carboxylate. In the final step

• , 1-pyrroline-5-carboxylate is reduced via the action of the pyrroline-5-carboxylate reductase proC, generating proline. Alternatively, glutamate semialdehyde can be created from ornithine via the action of a pyridoxal phosphate-dependent enzyme, the ornithine-oxo-acid aminotransferase rocD. Very

Helicene synthesis by Brønsted acid-catalyzed cycloaromatization in HFIP [(CF₃)₂CHOH]

• Takeshi Fujita,
• Noriaki Shoji,
• Nao Yoshikawa and
• Junji Ichikawa

Beilstein J. Org. Chem. 2021, 17, 396–403, doi:10.3762/bjoc.17.35

• for 40 min, the reaction was quenched with phosphate buffer (pH 7). Organic materials were extracted with CH2Cl2 three times, and the combined extracts were washed with brine and dried over Na2SO4. After removal of the solvents under reduced pressure, the residue was purified by silica gel column

• with phosphate buffer (pH 7). Organic materials were extracted with ethyl acetate three times, and the combined extracts were washed with brine and dried over Na2SO4. After removal of the solvents under reduced pressure, the residue was purified by silica gel column chromatography (hexane/CH2Cl2 = 3:1

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• /L ammonium chloride, 20 mL/L oleic acid, 10 g/L ᴅ-glucose, 2 g/L casamino acid, and 15 g/L bacto agar in 100 mM citrate–phosphate buffer at pH 5). The petri dishes were incubated for 48 h at 30 °C and then overlayered with a preparation of 1% (w/v) molten top agar containing the chromogenic

• enzyme. Liquid-medium-based colorimetric assays using 4NTC–linker–Fe (12) In a typical experiment, discontinuous enzyme assays were performed in triplicates under buffered conditions (100 mM sodium phosphate at pH 6.0) in the presence of 1.8 mM 12 and 3.6% DMSO, final concentrations. For the assay, this

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

Supramolecular polymerization of sulfated dendritic peptide amphiphiles into multivalent L-selectin binders

• David Straßburger,
• Svenja Herziger,
• Katharina Huth,
• Moritz Urschbach,
• Rainer Haag and
• Pol Besenius

Beilstein J. Org. Chem. 2021, 17, 97–104, doi:10.3762/bjoc.17.10

• containing 100 mM NaCl, over the phosphate buffer in PBS, since TRIS is known to avoid artefacts due to phosphate salts [42][43]. Cryo-TEM experiments were performed using solutions of II in PBS (−/−, containing 100 mM NaCl). All TEM and cryo-TEM micrographs clearly demonstrated the formation of long rigid

Synthesis, crystal structures and properties of carbazole-based [6]helicenes fused with an azine ring

• Daria I. Tonkoglazova,
• Anna V. Gulevskaya,
• Konstantin A. Chistyakov and
• Olga I. Askalepova

Beilstein J. Org. Chem. 2021, 17, 11–21, doi:10.3762/bjoc.17.2

• % ii) SPINOL-derived phosphoric acid, Amberlite CG50, CH2Cl2, −7 °C, 72 h, 74%; iii) chloranil, diphenyl phosphate, CHCl3, 50 °C, 5 h, 76%. Synthetic strategy for the carbazole-based [6]helicenes fused with an azine ring. Sonogashira coupling of compound 4b with phenylacetylene. i) Pd(PPh3)2Cl2, CuI

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• was prepared via the palladium-catalyzed reduction of the corresponding phosphate 17 [54]. Iodination and Sonogashira coupling, followed by acetylation led to the formation of the desired enynyl acetate 20. This compound was treated with 5 mol % Ph3PAuCl/AgSbF6 in DCM, and after 6 h, this afforded the

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• synthesis of biarenes has been developed. The approach is based on the photoextrusion of a phosphate moiety occurring upon irradiation of biaryl- and triaryl phosphates. The reaction involves an exciplex as the intermediate and it is especially suitable for the preparation of electron-rich biarenes

• metal-free eco-sustainable conditions we reinvestigated the photochemistry of di- and triaryl phosphates III and IV (Scheme 1e), compounds that can be easily achieved from the corresponding phenols [62][63]. Results and Discussion At the onset of our investigation, we tested a triaryl phosphate such as

• 4-chlorophenyl diphenyl phosphate (1a), as the model compound in different solvents by irradiation in a multilamp reactor (wavelength centered at 310 nm, see Supporting Information File 1 for details). The obtained results are depicted in Table 1. Compound 1a (0.02 M) was quite photostable in

Secondary metabolites of Bacillus subtilis impact the assembly of soil-derived semisynthetic bacterial communities

• Heiko T. Kiesewalter,
• Carlos N. Lozano-Andrade,
• Mikael L. Strube and
• Ákos T. Kovács

Beilstein J. Org. Chem. 2020, 16, 2983–2998, doi:10.3762/bjoc.16.248

• g⋅L−1 dipotassium hydrogen phosphate, and 2.5 g⋅L−1 glucose. Semisynthetic mock community assay Semisynthetic soil communities were obtained from the soil of sampling site P5 (55.788800, 12.558300) [51][64]. 1 g soil was mixed in a 1:9 ratio with a 0.9% saline solution, vortexed on a rotary shaker

Selected peptide-based fluorescent probes for biological applications

• Debabrata Maity

Beilstein J. Org. Chem. 2020, 16, 2971–2982, doi:10.3762/bjoc.16.247

• interacts effectively with double-stranded DNA (dsDNA) as positively charged lysine residues are expected to interact with the phosphate backbone electrostatically. Upon binding to dsDNA, it undergoes a conformational change from the folded to an extended form that switches the fluorescence signal from

• serum albumin. Other biomolecules such as adenosine, adenosine monophosphate, adenosine triphosphate, phosphate, pyrophosphate, glucose, heparin, hyaluronic acid and chondroitin sulfate, and amino acids containing two carboxylates (glutamic acid and aspartic acid) have not increased the fluorescence

• biological analytes including such as adenosine, adenosine monophosphate (AMP), adenosine triphosphates (ATP), phosphate (Pi), pyrophosphate (PPi), ct-DNA, glucose, bovine serum albumin (BSA), glutamic acid and aspartic acid. They are also selective over the similar biological analytes hyaluronic acid or

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• (resistivity ≥ 18 MΩ cm) and filtered through a membrane filter (0.45 µm pore size). K-phosphate-buffer (22AG, a2): 25 mM K2HPO4, 70 mM KCl; pH 7.0; Na-cacodylate buffer (F21T, Fa2T, FmycT, FkitT, and FkrasT): 90 µM LiCl, 10 mM KCl, 10 mM Na(CH3)2AsO2 × 3H2O, pH 7.2–7.3. The K-phosphate buffer solutions and

• in K+-phosphate buffer) was used as a cosolvent. For the CD spectra, solutions of G4-DNA in K+-phosphate butter and the ligands in buffer/DMSO were recorded after an equilibration time of 30 min. For the thermal DNA denaturation analyses stock solutions of the ligand (20 µM) and the G4-DNA (50 µM) in

• ; cDNA = 200 μM) in K+-phosphate buffer (pH 7.0) with 10% v/v DMSO). The arrows indicate the development of the absorption or emission bands with increasing DNA concentration. Insets: Plots of Abs./Abs.0 and I/I0, respectively, versus cDNA/c3c. Inset B1: Picture of the emission color and intensity of