Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• electron-withdrawing group that enhances the effects of many bioactive molecules due to a significant improvement in stability, lipophilicity, and resistance to enzymatic degradation [17][18]. Also, it has been widely applied as a special alkyl substituent for ligands of phosphorescent heavy metal

The ethoxycarbonyl group as both activating and protective group in N-acyl-Pictet–Spengler reactions using methoxystyrenes. A short approach to racemic 1-benzyltetrahydroisoquinoline alkaloids

• Marco Keller,
• Karl Sauvageot-Witzku,
• Franz Geisslinger,
• Nicole Urban,
• Michael Schaefer,
• Karin Bartel and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2716–2725, doi:10.3762/bjoc.17.183

• . Interestingly, macrocyclic bisbenzylisoquinolines such as tetrandrine [48][49] and related alkaloids [50], have been reported to inhibit P‐glycoprotein (P-gp), a crucial factor of multidrug resistance in cancer. This is noteworthy as multidrug resistance is still a major problem in cancer therapy and no

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

Isolation and characterization of new phenolic siderophores with antimicrobial properties from Pseudomonas sp. UIAU-6B

• Emmanuel T. Oluwabusola,
• Olusoji O. Adebisi,
• Fernando Reyes,
• Kojo S. Acquah,
• Mercedes De La Cruz,
• Larry L. Mweetwa,
• Joy E. Rajakulendran,
• Digby F. Warner,
• Deng Hai,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2021, 17, 2390–2398, doi:10.3762/bjoc.17.156

• ; pseudomonine; Pseudomonas sp.; vancomycin-sensitive Enterococcus faecium; Introduction The introduction of antimicrobial drugs in the mid-20th century has had an unprecedented positive impact on human health, but the current threat of multiple drug resistance may well roll back all these past achievements [1

Synthesis and antimicrobial activity of 1H-1,2,3-triazole and carboxylate analogues of metronidazole

• Satya Kumar Avula,
• Syed Raza Shah,
• Khdija Al-Hosni,
• Muhammad U. Anwar,
• Rene Csuk,
• Biswanath Das and
• Ahmed Al-Harrasi

Beilstein J. Org. Chem. 2021, 17, 2377–2384, doi:10.3762/bjoc.17.154

• cost-effective drug. Due to its impressive antimicrobial activity and limited adverse effect metronidazole (1) has been considered as a “Gold Standard” antibiotic (Figure 1). However, to avoid the problem related to clinical resistance to this antimicrobial agent some novel and improved analogues of

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• the transduction of signals; these processes induce cell apoptosis [8][9]. As mutations in the BCR-Abl-1 enzyme domain can occur, cases of resistance have emerged in the treatment with TKIs, compromising its effectiveness [10][11]. In continuation of the work by our group to develop new imatinib

• the 1,2,3-triazole core strategically in the design of new compounds [18][19]. The explanation for this interest is associated with its resistance towards oxidation, reduction, and acidic or basic hydrolysis reactions that occur in phase I of human metabolism [20][21]. The application of this core

• through isosterism (classical or non-classical) in the design of new active compounds has shown good results [22][23]. Specifically, in the development of new inhibitors for the treatment of cancer [24], its use is associated with producing compounds able to overcoming resistance (primary or secondary

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• nuclease resistance, increased binding to the nucleic acid target and improved cell uptake for oligonucleotides (ONs) and ASOs. The modifications highlighted in this review are some of the most prevalent cationic amine groups which have been attached as single modifications onto ONs/ASOs. The review has

• table design showing which modification has duplex stabilizing properties, as well as improved nuclease resistance and cell activity, has been chosen for optimal visual presentation. This approach has spurred considerable interest since the introduction of positively charged groups results in ASOs with

• membrane permeability of ASOs. A reduction in the net negative charge may have beneficial delivery-related effects in addition to other possible effects such as improved resistance towards nuclease degradation or increased binding to the negatively charged RNA complements, the latter as a result of reduced

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