Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• [72]. It was further shown to be cytotoxic and inhibiting cell cycle progression at G2/M phase [163]. Fumitremorgin C was shown to effect mammalian cells and inhibit the breast cancer resistance protein which imparts multidrug resistance and thus resistance to chemotherapeutics in breast cancer

• cross-resistance helvolic acid is of great pharmaceutical importance. On the other hand, these antibiotic activities of HA could alter the soil microflora in natural habitats, an ecological role of HA that requires further investigation. Pyripyropene A Pyripyropene A (PPPA) (24) belongs to the

• . fumigatus was driven by its pathobiology, e.g., a role in cytotoxicity, immunosuppression or antifungal drug resistance. In natural habitats these molecules may fulfill analogous functions, such as the defense against phagocytic predators by gliotoxin [78][79][80][81][82]. Indeed, the need for survival is

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

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• stability, and fluorescence properties. The incorporation of the double-headed nucleosides 151a–d and 154a,b into oligonucleotides failed to form thermostable duplexes with complementary DNA and RNA strands but exhibited a potential resistance towards 3′-exonuclease. The synthesized double-headed

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

• modifications provide improved resistance to degradation by exo- and endonucleases and they both affect protein binding [16][17]. Eight of the now approved 13 oligonucleotide drugs feature the PS modification in the backbone and all four approved siRNA therapeutics: ONPATTRO® (patisiran, 2018), GIVLAARI

• '-aminonucleoside couples to the 5'-H-phosphonate in the presence of a base (Scheme 1) [64]. In comparison with natural phosphodiester oligonucleotides, these modified oligonucleotides display improved nuclease resistance and an enhanced duplex thermal stability of 2.3–2.6 °C per linkage independent of nucleotide

• the 3'-overhang region show enhanced endonuclease and 3'-exonuclease resistance [80]. Thus far, the AM1 modification has not found great success in antisense therapeutics, owing to RNAse H not recognizing a uniformly modified AM1-DNA:RNA heteroduplex. Recently, however, an 18-mer AM1-DNA gapmer was

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

• , we used a HEK293T cell line engineered to express gp160 [45], HEK293T-gp160, and the parental HEK293T served as a control cell line. hCMEC/D3 cells were cultured on a 0.4 µM transwell mesh until a trans-endothelial electrical resistance of above 30 Ω⋅cm2 was reached. This measure is an indicator that

• ) or TZM-bl (CCR5-positive cell type) cells (A and B) as well as HEK293T or gp160 positive HEK293T cells (C and D) were seeded at a density of 50,000 cells/well. The next day, transwell inserts containing confluent hMEC/D3 cells at trans-endothelial electrical resistance (TEER) above 30 Ω⋅cm2 were

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

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

• responsible for the stabilisation of duplexes with N+ modification. N+ONs also demonstrated greater resistance to nuclease digestion by snake venom phosphodiesterase I than the corresponding Ts-ONs. Cell uptake studies showed that Ts-ONs can enter the nucleus of mouse fibroblast NIH3T3 cells without any

• ]. The major challenge in designing chemically modified ONs as antigene/antisense agents is to ensure an efficient cellular uptake and nuclease resistance while still maintaining, or ideally increasing, binding affinity and specificity of the ONs towards their DNA or RNA target. Many synthetic analogues

• 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

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• obesity and insulin resistance [36]. Glycologue web application The Glycologue ganglioside simulator is available at https://glycologue.org/g/, along with the source code of the simulator in the Python programming language. Glycologue exports networks as SBML, for import into Copasi [37], CellDesigner [38

β-Lactamase inhibition profile of new amidine-substituted diazabicyclooctanes

• Zafar Iqbal,
• Lijuan Zhai,
• Yuanyu Gao,
• Dong Tang,
• Xueqin Ma,
• Jinbo Ji,
• Jian Sun,
• Jingwen Ji,
• Yuanbai Liu,
• Rui Jiang,
• Yangxiu Mu,
• Lili He,
• Haikang Yang and
• Zhixiang Yang

Beilstein J. Org. Chem. 2021, 17, 711–718, doi:10.3762/bjoc.17.60

• mechanisms [1] in microorganisms ultimately leading to the initiation of antibiotic resistance and survival of the microorganisms [2]. In case of Gram-negative pathogenic bacteria, production of β-lactamases [3] is the main arsenal of these microorganisms against antibiotics. The number of β-lactamases is

• case of the ceftazidime/avibactam combination due to overproduction of AmpC cephalosporinases [26]. In another report it has been concluded that ESBLs of the GES, PER and BEL types in E. coli and P. aeruginosa conferred resistance against sulbactam and avibactam combinations [27]. Therefore, it is

• utmost necessary to continue the struggle with exploring new inhibitors capable of improved resistance and activity against all classes of β-lactamases. Based on our ongoing efforts towards the synthesis of new DBO-based BLIs, we have synthesized a number of amidine-conjugated derivatives of avibactam

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• -lactams are important lead compounds, e.g., derivatives with antibacterial activity were discovered, what gains importance with respect to the increasing bacterial resistance toward traditional β-lactam antibiotics [35][36][37][38][39]. Various synthetic pathways can be applied for the construction of the

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

• ]. The S-cEt-modified ASOs displayed a higher nuclease resistance and lower hepatotoxicity in in vivo experiments than the corresponding 2',4'-BNA/LNA-modified ASOs [9]; the reduction in hepatotoxicity might be a sequence-dependent phenomenon. Currently, a number of S-cEt-modified ASOs with low

• hepatotoxicity have been confirmed to be effective for gene regulations in vivo [10][11]. We previously developed amido-bridged nucleic acids (AmNA[R]s) (Figure 1), in which the N-alkyl substituent groups were found to modulate nuclease resistance and hepatic distributions [12]. Wengel’s group reported the

• ]. The modification of oligonucleotides with GuNA[H]-T improved the nuclease resistance, cell membrane permeability, and binding affinity toward complementary single-stranded DNAs (ssDNAs) and RNAs (ssRNAs). We also synthesized and evaluated a GuNA[H]-T analog bearing a methyl group in the guanidine

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• Polyolefins Due to the intrinsic chemical resistance of the hydrocarbon skeleton devoid of functional groups, polyolefins are neither prone to chemical recycling nor biodegradable [131][132]. Hence, they are more commonly repurposed via mechanical recycling, burned or just discarded [133][134

• –0.97 g⋅cm−3, Tm 130 °C) is a highly crystalline material with a low degree of short chain branching. Owing to the high stiffness, tensile strength, resistance to moisture and gas permeability, it is mainly used in the manufacture of water pipes, toys, beverage bottles, outdoor furniture, housewares and

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• phosphonodepsidipeptides 121 from N-Cbz-1-amino-2-phenylethylphosphonic acid (119) and hydroxy esters 120 in the presence of diisopropylethylamine (DIPEA) in CH2Cl2 (Scheme 20) [35]. Vancomycin resistance became a serious health care problem currently. The development of a catalytic monoclonal antibody to hydrolyze the

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

• Yamato Fujihira,
• Yumeng Liang,
• Makoto Ono,
• Kazuki Hirano,
• Takumi Kagawa and
• Norio Shibata

Beilstein J. Org. Chem. 2021, 17, 431–438, doi:10.3762/bjoc.17.39

• necessary, and the resistance of the reaction was also verified from various pharmacophores to be acceptable. Conclusion In conclusion, the trifluoromethylation of methyl carboxylates to trifluoromethyl ketones is accomplished under basic conditions with fluoroform in triglyme at −40 °C. An equivalent

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

• tactic in the battle against antimicrobial resistance. In addition to fluorinated metabolites that are produced de novo from fluoride ions, it is possible to modify other secondary metabolites to incorporate fluorine by including fluorinated precursors in the culture medium. 19F NMR has been applied to

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

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• showed no interaction with Au(III), as expected. A similar resistance to coordinate was observed for the open diamides 1c–e. The phosphorus containing ligand 1c did undergo phosphorus oxidation instead of Au(III) coordination. No effect was obtained by refluxing or by adding additives, such as silver

• cyclam tetraamino-coordination was obtained by 1H,15N-HMBC NMR. The polyamides (1, 2) failed to undergo Au(III) coordination, which confirmed the previously observed resistance of amides to coordinate to Au(III). The catalytic ability of the new Au(III) complexes were screened in selected test reactions

Synthesis of aryl 2-bromo-2-chloro-1,1-difluoroethyl ethers through the base-mediated reaction between phenols and halothane

• Yukiko Karuo,
• Ayaka Kametani,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2021, 17, 89–96, doi:10.3762/bjoc.17.9

• agrochemical sciences because deliberately incorporated fluorine atoms often change the chemical properties of the parent molecules by improving the absorption, resistance to metabolism, and pharmacological activities. To date, difluoromethyl or difluoromethylene compounds have been studied extensively as well

One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity

• Giovanna Bosica,
• Kaylie Demanuele,
• José M. Padrón and
• Adrián Puerta

Beilstein J. Org. Chem. 2020, 16, 2862–2869, doi:10.3762/bjoc.16.235

• the general procedure. Biological screening The 1,4-DHP scaffold displays an extensive range of biological activities, including reversing multidrug resistance (through the inhibition of the P-glycoprotein) [26] and antiproliferative effects on human cancer cell lines [27]. We wondered whether the

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

Palladium nanoparticles supported on chitin-based nanomaterials as heterogeneous catalysts for the Heck coupling reaction

• Tony Jin,
• Malickah Hicks,
• Davis Kurdyla,
• Sabahudin Hrapovic,
• Edmond Lam and
• Audrey Moores

Beilstein J. Org. Chem. 2020, 16, 2477–2483, doi:10.3762/bjoc.16.201

• resistance to reduction was surprising and in contradiction to what we observed with deposition onto CNC of Pd in the presence of H2 [7], or Ag alone [20]. The striking difference between CNC on one hand and ChNC/ChsNC on the other is the presence of carboxylates on the latter. Carboxylates are expected to

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• lipophilicity with the molecular conformation. Keywords: dipole moment; fluorinated compounds; gauche effect; herbicides; log P; Introduction Whilst in the last years the agrochemical industry has encountered a period of downturn affected by new regulations, low crop prices, biochemical resistance, among

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• at higher concentrations can be explained by the intermolecular coordination, which stabilizes the trans isomer. Long-term switching experiments were performed to investigate the fatigue resistance of 1. In contrast to other record player molecules, which are stable up to 100 000 switching cycles

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• resistance and geometric capacitance were attributed to the high-frequency semicircle. The membrane bulk resistance and geometric capacitance were heavily influenced by the properties of the plasticizer, DOS (εr = 4.01 [34]), because it accounted for most of the mass in all of the membranes. The bulk

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

• cause environmental pollution, resistance in plant pathogens as well as high production costs of crops [1][2][3]. Varieties of crop plants have symbiotic relationships with microorganisms by hosting them in their roots and utilize their beneficial effects such as improving the quality of soil and

• nitrogen fixing capabilities, Azospirillum produce a number of plant-growth-promoting vitamins and phytohormones [9][10]. Their potential to promote resistance towards bacterial infections in rice was also documented [11]. The potential of stimulating plant-growth-related biochemical processes of