Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• to dsDNA [1][2]. The parallel PNA-dsDNA triplex, where the N-terminus of PNA aligns with the 5′-terminus of a polypurine strand of DNA (Figure 2A), is a binding mode that is particularly sensitive to electrostatic repulsion as three negatively charged strands are brought in proximity. PNA was also

• Rozners and co-workers showed that PNAs as short as hexamers formed strong and sequence specific triplexes at pH 5.5 [27]. Later studies using nucleobase-modified PNA (vide infra) confirmed that PNA had >10-fold higher affinity for dsRNA than for the same sequence of dsDNA [28][29][30][31]. While parallel

• for antiparallel triplexes. The strand invasion complex contains two PNA molecules binding the purine-rich strand of DNA. While one PNA strand forms an antiparallel Watson–Crick duplex, the other strand forms a parallel Hoogsteen triplex, which brings the N- and C-ends of the two strands in proximity

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• observed by parallel experiments, again suggesting that the C‒H activation is kinetically relevant (Scheme 4d). Based on our mechanistic findings and previous studies, we propose a tentative plausible reaction pathway in Scheme 5. The transformation commences with substrate coordination and subsequent

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• ®, Europe) [47]. This inoculum solution is referred to as the 1:10 dilution. The in vivo experiments were immediately initiated after preparing the inoculums. Simultaneously, uninfected shrimp or free WSSV were parallel-used under the same procedure as a negative control (WSSV-negative). Viral inoculum

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• SYBR Gold staining (Figure 3a) as previously described [8][37]. These findings indicated that bacteria are associated with their algal host during symbiosis. In parallel, we visualised the metabolites produced by the biofilm formed around U. mutabilis by imaging analysis with AP-SMALDI-HRMS. Three

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• system with the steam being recycled back through the reactor. After phase separation, the obtained mixture was enriched to 85% of 83 (equating to a 73% isolated yield). Once the reaction conditions were optimised, the apparatus can merge with other flow systems to develop a parallel continuous multistep

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• ]. Compound 13 is a recollection of the older sample 13A and is almost identical in structure. Both feature a parallel alignment of porphyrins tied together with the reciprocated Br···H contacts with the pyrrole hydrogens and a second contact between the bromine and the p-methoxy hydrogens (Figure 17A, Figure

•  18A). Both structures also feature the hexyl chain overlapping with the face of the porphyrin ring (Figure 17B, Figure 18B, Supporting Information File 1, Figure S35). Compound 14 forms a similar parallel alignment as the one seen in compounds 13 and 13A (Supporting Information File 1, Figure S36A

• Information File 1 (Figure S43 and Figure S44). The hydrogen···halogen interactions are listed in Table 2. Compounds 16–18 are a series of structures that only differ by the type of metal center in the porphyrin core [34][35]. In compound 16 the stacked porphyrin layers are orientated in a parallel

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

• oxazolidin-2-one 9. NOESY experiments and X-ray structure proofment of the structure of oxazolidine 17. Proposed pathway for the ring–ring tautomerism. Stereoselective synthesis of the pinane-fused oxazolidin-2-one 9. Stereoselective synthesis of the pinane spiro-fused oxazolidin-2-one 12. Parallel synthesis

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