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

• °C) [99][101]. Moreover, (S)-GNA and (R)-GNA do not cross-pair either in a parallel or antiparallel fashion; thus GNA:GNA duplex formation is limited to homochiral pairing between either (S)-GNA or (R)-GNA strands [103]. With respect to nuclease stability, Nielson et al. showed that a 17mer

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

• , multimode microwave reactors for parallel synthesis and multimode microwave reactors for single-batch scale-up. The reactors vary in capacity and the distribution mode of the electromagnetic wave in the reactor vessel. The introduction of the Si–C (silicon–carbon) vials enables high temperature resistance

• seems to be compromised imposing restrictions on using microwaves at a scale-up level. However, the batch process and continuous flow process seem to provide an entry into scale-up standards with safety. The microwave reactors serving the purpose of batch and parallel approach are designed in various

A chromatography-free and aqueous waste-free process for thioamide preparation with Lawesson’s reagent

• Ke Wu,
• Yichen Ling,
• An Ding,
• Liqun Jin,
• Nan Sun,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2021, 17, 805–812, doi:10.3762/bjoc.17.69

• ]. This method with long perfluorinated alkyl chains is attractive in parallel synthesis and also in high-throughput biological screening. However, both the modified LR and the fluorous solvents are rather expensive and not practical for scaling up. Besides, basic aqueous solutions were utilized as well

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

• provide either a zwitterionic phosphoramidate with N+ modification or a negatively charged phosphoramidate for Ts modification in the DNA sequence. The incorporation of these N+ and Ts modifications led to the formation of thermally stable parallel DNA triplexes, regardless of the number of modifications

• parallel triple-helix structure, a polypyrimidine TFO binds to dsDNA through Hoogsteen base-pairing [17], in which the cytosine bases in the TFO are protonated at the N3 atom (Figure 1B). In antisense strategies, antisense ONs (AOs) interact with RNA molecules to interfere with protein expression [18][19

• various positions in the sequence. The thermal stability of a parallel DNA triplex and duplexes of DNA and RNA formed with these ONs where then evaluated. Thermal denaturation experiments, nuclease resistance and cell-uptake assays were also conducted to evaluate these chemically modified ONs. Results

Synthesis of dibenzosuberenone-based novel polycyclic π-conjugated dihydropyridazines, pyridazines and pyrroles

• Ramazan Koçak and
• Arif Daştan

Beilstein J. Org. Chem. 2021, 17, 719–729, doi:10.3762/bjoc.17.61

• reaction conditions. Inverse electron-demand Diels–Alder reactions are cycloadditions between electron-rich dienophiles and electron-poor dienes. EDGs raise the electron density of dienes and, in parallel, raise the LUMOdiene–HOMOdienophile energy gap, and consequently the reactivity decreases. Although

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• diacylation reactions were run in parallel and then combined for oxidative hydrolysis. The quantities for each reaction are separated by a forward slash. To a mixture of 3-aminopyrrolizine hydrochloride 17 (22.3/43.6 mg, 0.118/0.231 mmol) and a solution of distilled pyridine in acetonitrile (1.20/2.30 mL, 0.5

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

• ) and for the incorporation of 5-fluorotryptophan (1) and 6-fluorotryptophan (2) in streptavidin [14]. Parallel to the development of these new strategies for recombinant fluorinated protein production, significant efforts have been made within the last decade to expand the pool of available amino acids

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• compared the reaction outcome and rates when DMSO-d6 solutions of the starting materials 2a and 2b were treated either with NaN3 or NaCl in parallel experiments. The reaction mixtures were directly analyzed by 1H and 31P NMR spectroscopy using 1,2,3-trimethoxybenzene as an internal standard (Tables S1 and

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• present (Scheme 6). Conclusion In conclusion, we have developed novel, complementary multi-parallel synthetic routes permitting the exploitation of the C-3 then C-4 vectors or vice versa to deliver our library of novel 3,4-disubstituted pyridin-2(1H)-one kinase inhibitors starting from readily-available 2

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

• to carry out a complete computational analysis to evaluate the entire reaction profile and to help us validate our hypothesis before embarking on a potential total synthesis, involving such a process, in the future. In parallel, a few suitable substrates were also subjected to gold catalysis with the

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

• . subtilis P5_B1 WT and the corresponding NRP mutant derivatives were inoculated in 0.1 × TSB and incubated in parallel using the same conditions. After 12 h precultivation, 3 mL aliquots of the soil suspension were transferred into six glass tubes. One tube was left untreated and functioned as control

Naphthalonitriles featuring efficient emission in solution and in the solid state

• Sidharth Thulaseedharan Nair Sailaja,
• Iván Maisuls,
• Jutta Kösters,
• Alexander Hepp,
• Andreas Faust,
• Jens Voskuhl and
• Cristian A. Strassert

Beilstein J. Org. Chem. 2020, 16, 2960–2970, doi:10.3762/bjoc.16.246

• parallel (see Figure 2B), the centroid distance between the rings reaches up to 4.985 Å, suggesting that the intermolecular π–π interactions are absent. In addition to these interactions, there also exist weak supramolecular N–H interactions. Firstly, two Me units form dimeric structures that are connected

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• sufficient for the parallel disassembling and assembling of the nanodevices through the sequential two-component translocation. The potential of the networking system was further extended to a seven-component system, in which a selective translocation had to occur with one out of the two bipeds (Figure 11c

• reactions in a double self-sorting protocol [60]. The operation of the network required the addition and removal of zinc(II) ions which triggered three distinct events in parallel: i) a mutually dependent self-sorting of different nanorotors and reshuffling of the components, ii) a switching between vastly

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• first instance, it seems difficult to parallel this for 2, but if for the first steps after ionisation to 2•+ a skeletal rearrangement to t2•+ and a hydrogen transfer to u2•+ are assumed, the parallelism of the fragmentation mechanisms becomes more obvious (Scheme 4C). Subsequent steps may include an

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

• temperature than the other ones. Most notably, the representative DNA denaturation analysis with ligand 4e and different quadruplex forms clearly reveals a significant selectivity. Hence, the hybrid antiparallel G4-DNA 22AG as well as the parallel quadruplex-forming KRAS sequence are stabilized to a

• significantly more extent than the parallel c-kit, c-myc or the mixed parallel/antiparallel a2 sequence. Therefore, it is concluded that the selectivity of the ligands does not depend on the direction of the strands, i.e., parallel versus antiparallel, but on the loop structure of the respective quadruplex form

• between the parallel and antiparallel quadruplex form only slightly in favor of the parallel structure, as is shown by a small increase of the positive CD signal at 295 nm, that is assigned to the parallel quadruplex [61][62], along with a decrease of the CD signal of the antiparallel form at 265 nm

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• scaling up can be achieved by numbering up. One of the most used photomicroreactors are capillaries wrapped around a light source. Such microcapillaries can be scaled up by connecting them either in parallel or in series (Figure 3a and Figure 3b). In a previous study, five polymer-based microcapillaries

• -benzophenone (DMBP) was studied. A single multisyringe pump was used to supply the reactants to the photomicroreactors. This kind of scaling up is called external numbering up since each reactor is fed directly by the pump. This numbering-up strategy allowed to run ten parallel microreactors at the same time

• . This microreactor setup used 30% less energy than the batch reactor, without the requirement of cooling [31]. The PSTY in this paper was calculated based on the same reaction being performed at the same time in ten parallel reactors (Table 1, entry 1). The reactions that are presented in Table 1 are

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• transition dipole moment with respect to the DNA chiral axis [50]. A positive sign observed for 3a suggests that the long axis of the NDI chromophore is perpendicular to the longitudinal axis of the base pairs (red arrow in Figure 8, for 3a), while a negative one observed for 3b suggests a parallel

• predominantly a parallel orientation for all dyes as shown in Figure 8 for the DNA–3b complex. The absence of any measurable ICD signal for poly(A)-poly(U) (ds-RNA) (Supporting Information File 1, Figure S26) supports the intercalation of all NDI chromophores at approximately 45° with respect to the base pair

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• experimental data that the basicity reduction from substituents that are parallel and perpendicular to the pyrrolidine ring are different. There are examples showing that the C–F or C–CF3 fragment in plane with the ammonium dipole reduces the basicity by about ΔpKa ≈ 2.2 [72][73]. The same value was obtained

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• previous functionalization, thus considerably reduce waste generation and a number of synthetic steps. In parallel, transformations involving photoredox catalysis promote radical reactions in the absence of radical initiators. They are conducted under particularly mild conditions while using the visible

• previously inaccessible molecules could be expected. C–H activation reactions, generally do not change the oxidation state of the metal and are favored in the case of aromatic or vinylic substrates but are clearly more challenging when using aliphatic precursors [21][22][23][24][25][26][27][28]. In parallel

• concerned the development of “classical” C–H activation reactions, while a photoredox cycle was implemented to reoxidize the metal catalyst, thus obviating the need for a stoichiometric amount of metal-based oxidants, such as silver or copper salts. In parallel, dual synergistic catalysis has emerged. In

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• with radioactively labeled substrates, the use of fluorescently labeled probes offers several advantages, including the continuous monitoring of the transport and a better time resolution. For reasons of comparison, the α-configured ᴅ-mannose probe MPC-3 was synthesized in parallel. The

Synthesis of the tetrasaccharide repeating unit of the O-specific polysaccharide of Azospirillum doebereinerae type strain GSF71^T using linear and one-pot iterative glycosylations

• Arin Gucchait,
• Pradip Shit and
• Anup Kumar Misra

Beilstein J. Org. Chem. 2020, 16, 1700–1705, doi:10.3762/bjoc.16.141

• obtained following the sequential glycosylation strategy (Scheme 2). It is noteworthy that in parallel to the sequential glycosylation strategy, the desired tetrasaccharide derivative 7 could be achieved in comparably good yield following the one-pot protocol involving the three iterative glycosylations

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• could exist in parallel to the bonding models used and discussed in teaching and research. This, however, would waste a unique opportunity to rationalize chemical thinking and communication and to establish the concept of models as the language of chemistry. The major requirements of a chemical ontology

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• the parallel dimer of CHC (p(CHC)2), which binds two molecules of the neurotransmitter N-acetylneuraminic acid (NANA) in a cooperative fashion (K1 = 143, K2 = 5.1 × 103 M−1). Recently we rationalized that since our peptide building blocks consist of the same binding motifs as binding proteins (amines

• tripeptide dimers can be found after equilibration. We note that this simple mixture of 4 peptides contains 10 different homo- and heterodimer combinations. In addition, since our building blocks are asymmetrical, parallel and antiparallel constitutional isomers are formed (Scheme 1b), which raises the total

• a) p(CFC)2 to YY b) p(CFC)2 to FF c) a(CFC)2 to YY d) a(CFC)2 to FF. Job plots derived from the continuously varied NMR measurements of a) p(CFC)2 to YY b) p(CFC)2 to FF c) a(CFC)2 to YY d) a(CFC)2 to FF. a) Building blocks included in this study. b) Antiparallel and parallel constitutional isomers

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• 8b/7c and 8c/7c (Figure 4a,b and Supporting Information File 1, Appendix 6). All the observable π···π interactions were parallel-displaced (offset) π-stacking, and the distance values were within the range of the known values, whether determined from X-ray structures or calculated values (3.2–4.0 Å

The charge-assisted hydrogen-bonded organic framework (CAHOF) self-assembled from the conjugated acid of tetrakis(4-aminophenyl)methane and 2,6-naphthalenedisulfonate as a new class of recyclable Brønsted acid catalysts

• Svetlana A. Kuznetsova,
• Alexander S. Gak,
• Yulia V. Nelyubina,
• Vladimir A. Larionov,
• Han Li,
• Michael North,
• Vladimir P. Zhereb,
• Alexander F. Smol'yakov,
• Artem O. Dmitrienko,
• Michael G. Medvedev,
• Igor S. Gerasimov,
• Ashot S. Saghyan and
• Yuri N. Belokon

Beilstein J. Org. Chem. 2020, 16, 1124–1134, doi:10.3762/bjoc.16.99

• crystals were a typical druse setup. Type 2 were well-formed, nonisotropic crystals with two parallel planes in varying sizes (0.3 × 0.4 × 1 mm). The thermogravimetric analysis and differential scanning calorimetry (TGA-DSC) of F-1 was conducted to examine its thermal properties. The TGA curve of the bulk