Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

• Gábor Benkovics,
• Mihály Bálint,
• Éva Fenyvesi,
• Erzsébet Varga,
• Szabolcs Béni,
• Konstantina Yannakopoulou and
• Milo Malanga

Beilstein J. Org. Chem. 2019, 15, 710–720, doi:10.3762/bjoc.15.66

• -difunctionalization; regioselectivity; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-D-glucopyranose (Figure 1 illustrates the heptamer, β-CD) that have attracted worldwide interest in various fields of applied supramolecular chemistry due to their ability to form host–guest inclusion complexes [1]. A

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• prey–predator relationship, the common symbiotic organisms in the algae and the soft corals might be the source of these metabolites. In fact, many investigations have proved that [23] numerous natural products are actually produced by microbes and/or microbial interactions with the “host from whence

Polyaminoazide mixtures for the synthesis of pH-responsive calixarene nanosponges

• Antonella Di Vincenzo,
• Antonio Palumbo Piccionello,
• Alberto Spinella,
• Delia Chillura Martino,
• Marco Russo and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2019, 15, 633–641, doi:10.3762/bjoc.15.59

• nanosponge materials with tunable properties. Nanosponges (NSs) [7][8][9][10][11][12][13][14] are hyper-cross-linked polymers or copolymers obtained by reacting supramolecular host species as the monomer units with suitable reticulating agents. Of course, the structural, physical and chemical features of the

• obtained material critically depend on the host monomer and the linker used, on their molar ratio and, in the case of copolymers, on the molar ratio between the parent comonomers. Therefore, by a proper choice of the components, tunability in the properties of the materials obtained can be achieved. In

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• recognition by pathogen-recognition receptors during L. major-induced leishmaniasis. Keywords: adjuvant; carbohydrates; L. major; microparticle; PAMP; Introduction Recognition of parasite cell surface molecules by host immune cells initiates the first step in the immune response [1][2]. The host’s immune

• system recognizes parasite surface glycoconjugates, or pathogen-associated molecular patterns (PAMPs), to build an immune response against the parasite and impede disease progression. Antigen presenting cells (APCs) recognize these PAMPs as pathogenic as compared to host glycans making these moieties

• ). The World Health Organization estimates that this neglected tropical disease causes between 1–2 million new cases annually [4]. Leishmaniasis manifests into three different forms, cutaneous, mucosal, or visceral, depending on parasite species, host immune system and location of infection [5

Back to the future: Why we need enzymology to build a synthetic metabolism of the future

• Tobias J. Erb

Beilstein J. Org. Chem. 2019, 15, 551–557, doi:10.3762/bjoc.15.49

• respect to their complexity (Figure 1), these classical metabolic engineering approaches can be classified as level 1 efforts, i.e., the optimization of a natural pathway in a native organism, or level 2 efforts, i.e., the transplantation or reconstruction of a natural pathway in a new host organism [11

• avoided some problems upfront [58]. Yet, it needs to be mentioned that even if complex synthetic metabolic networks can be realized in vitro, this does not mean that these metabolic networks can be easily transplanted into living cells. The introduction of new reactions and metabolites into a host cell is

• expected to create interactions with the native metabolic and regulatory network of the host. Again, promiscuity poses a major challenge. Even though the metabolites and reactions might be completely non-native to the cell, these intermediates might be still drained due to unwanted side reactions or create

Aqueous olefin metathesis: recent developments and applications

• Valerio Sabatino and
• Thomas R. Ward

Beilstein J. Org. Chem. 2019, 15, 445–468, doi:10.3762/bjoc.15.39

• (Figure 1c) through host–guest interactions [61]. Chung and co-workers used a PEG-tethered adamantyl ligand for various metathesis reactions in water and DCM [62]. The authors showed that the catalyst can be easily removed by generating a host–guest complex between silica-grafted β-cyclodextrin and the

• through host–guest interaction with silica-gel-supported β-cyclodextrin. Selection of artificial metathases reported by Ward and co-workers (ArM 1 based on biotin–(strept)avidin technology and ArM 2 based on dative anchoring to hCAII). Artificial metathase based on covalent anchoring approach. α

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• Pseudomonas cichorii causes varnish spots on lettuce. Varnish spots, also called midrib rot or bacterial rot [1][2][3][4], are dark brown and can induce necrotic lesions [1][2][3][4][5][6][7]. P. cichorii, isolated by us, infects a wide range of host plants, including monocot and dicot species (e.g

Fabrication of supramolecular cyclodextrin–fullerene nonwovens by electrospinning

• Hiroaki Yoshida,
• Ken Kikuta and
• Toshiyuki Kida

Beilstein J. Org. Chem. 2019, 15, 89–95, doi:10.3762/bjoc.15.10

• supramolecular fiber materials composed of cyclodextrin (CD)–fullerene inclusion complexes by electrospinning. Similar to the molecular state of fullerenes in solution, the resulting fibers include molecularly-dispersed fullerenes. We believe such a concept could be expanded to diverse host–guest complexes

• functionalize such fibers is to use host–guest inclusion complexes in CD electrospinning. To date, Uyar and Celebioglu have reported electrospinning of two different inclusion complexes: hydroxypropyl-β-CD (HP-β-CD)–tricosan [16] and HP-β-CD–azobenzene inclusion complexes [17]. Although such complexes are

• abilities for free radical scavengers and solar cell applications [18][19][20]. A serious issue for practical applications of fullerenes is the poor solubility in most solvents. Various methods to improve the solubility have been demonstrated by coating the surface with surfactants or host molecules and

Lectins of Mycobacterium tuberculosis – rarely studied proteins

• Katharina Kolbe,
• Sri Kumar Veleti,
• Norbert Reiling and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2019, 15, 1–15, doi:10.3762/bjoc.15.1

• biology and identify new drug targets and anti-Mtb strategies. Mtb bacteria are mainly transmitted by inhalation of aerosolized droplets released from infected patients by coughing. The infection process is initiated by contact between inhaled bacteria and host cells within the alveolar airspace. The main

• invasion of host cells is a complex process, which is initiated by interactions between host and bacterial cell surface structures. As shown in previous studies, host cells can bind to mycobacterial cell wall carbohydrates via a class of surface-localized or secreted proteins known as lectins, and these

• -SIGN) [28][29], the dendritic cell-specific C-type lectins (Dectin-1, Dectin-2) [30][31], the macrophage inducible C-type lectin (Mincle) [32][33][34], the macrophage C-type lectin (MCL) [35][36], and the mannose receptor (MR) [37][38] (Figure 1). Since the importance of host lectins in Mtb infection

Repurposing the anticancer drug cisplatin with the aim of developing novel Pseudomonas aeruginosa infection control agents

• Mingjun Yuan,
• Song Lin Chua,
• Yang Liu,
• Daniela I. Drautz-Moses,
• Joey Kuok Hoong Yam,
• Thet Tun Aung,
• Roger W. Beuerman,
• May Margarette Santillan Salido,
• Stephan C. Schuster,
• Choon-Hong Tan,
• Michael Givskov,
• Liang Yang and
• Thomas E. Nielsen

Beilstein J. Org. Chem. 2018, 14, 3059–3069, doi:10.3762/bjoc.14.284

• induced expression of ptrB, a repressor of T3SS by cisplatin treatment (Supporting Information File 1, Table S3). The T3SS is one of the major virulence mechanisms employed by P. aeruginosa and other microbial pathogens to impair the host immune systems during infection [36][37]. T3SS activity of P

• . aeruginosa was correlated with acute cytotoxicity to host epithelial cells and immune cells such as macrophages and neutrophils [38]. As we demonstrated that cisplatin treatment was able to reduce the T3SS of P. aeruginosa, we further tested the ability of cisplatin in attenuating the acute cytotoxicity of P

MoO₃ on zeolites MCM-22, MCM-56 and 2D-MFI as catalysts for 1-octene metathesis

• Hynek Balcar,
• Martin Kubů,
• Naděžda Žilková and
• Mariya Shamzhy

Beilstein J. Org. Chem. 2018, 14, 2931–2939, doi:10.3762/bjoc.14.272

• cups as we assume host MoOx species. Although MCM-56(13) as 2D zeolite consists of very thin layers, these layers may be curled and packed, which prevents the access of substrate molecules to the most of 12MR cups (for MCM-56(13) morphology see Supporting Information File 1, Figure S8). This may

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• are other strategies that are being explored towards the discovery of new antibiotics with novel mechanisms of action such as for example inhibitors of host–pathogen interactions and of the type 3 secretion system (T3SS) in Gram-negative bacteria, nonetheless, the specific targets remain unknown or

Enhanced single-isomer separation and pseudoenantiomer resolution of new primary rim heterobifunctionalized α-cyclodextrin derivatives

• Iveta Tichá,
• Gábor Benkovics,
• Milo Malanga and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2018, 14, 2829–2837, doi:10.3762/bjoc.14.261

• ; heterobifunctionalized alpha-cyclodextrin; homobifunctionalized alpha-cyclodextrin; regioisomers; regioselectivity; Introduction Cyclodextrins, cyclic cone-shaped oligosaccharides [1], have long attracted interest for their properties in host–guest complexes both in research and in pharmaceutical and food industry

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• hypothesized that by “disarming” the pathogen, rather than inhibiting its growth, selective pressure for resistance development will be much lower. Furthermore, reduction of bacterial virulence directly protects the host, and at the same time renders the bacteria more susceptible towards the host defense

Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow

• Clémentine Minozzi,
• Jean-Christophe Grenier-Petel,
• Shawn Parisien-Collette and
• Shawn K. Collins

Beilstein J. Org. Chem. 2018, 14, 2730–2736, doi:10.3762/bjoc.14.251

• organic halide from the corresponding alcohol (Figure 1) [6][7]. The Appel reaction is representative of a host of transformations that require stoichiometric reagents to effect a functional group change of an alcohol. In 2011, Stephenson and co-workers reported that photocatalysis could be used to

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• their phenotype in response to changes in population density, regulating virulence and biofilm formation when most impactful to the host organism [5]. This process is mediated by signalling molecules such as PQS, and natural product structures 1–8 analogous to PQS may provide interspecies QS-modulator

Non-native autoinducer analogs capable of modulating the SdiA quorum sensing receptor in Salmonella enterica serovar Typhimurium

• Matthew J. Styles and
• Helen E. Blackwell

Beilstein J. Org. Chem. 2018, 14, 2651–2664, doi:10.3762/bjoc.14.243

• , host colonization, and biofilm formation at high population densities. This cell–cell signaling process is regulated by N-acyl L-homoserine lactone (AHL) signals, or autoinducers, and LuxR-type receptors in Gram-negative bacteria. SdiA is an orphan LuxR-type receptor found in Escherichia, Salmonella

• , Klebsiella, and Enterobacter genera that responds to AHL signals produced by other species and regulates genes involved in several aspects of host colonization. The inhibition of QS using non-native small molecules that target LuxR-type receptors offers a non-biocidal approach for studying, and potentially

• to coordinate group beneficial behaviors such as virulence factor production, host colonization, and biofilm formation at high population densities [12]. Gram-negative bacteria typically use N-acyl L-homoserine lactone (AHL) signals for QS, which are produced by LuxI-type synthases and sensed by

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• and other pathogenicity traits to overwhelm and colonise the host in the infection process [5] and pqs QS plays a crucial role in the regulation of many of those. It is astonishing, that expression of 182 genes is altered in response to exogenous PQS [33]. Evidence has been gathered, that these

• molecule [34]. This autoinducer has been described to mediate iron acquisition, cytotoxicity, outer-membrane vesicle biogenesis, and to exert host immune modulatory effects [34][35]. Interestingly, PQS as well as HHQ are able to interfere with nuclear transcription factor-κB and hypoxia-inducible factor 1

• (HIF-1) signaling pathways and, thus, down-regulate host innate immune systems [36][37]. Other PQS-related metabolites have been shown to have additional effects. HQNO, for example, induces autolysis and release of extracellular DNA thereby promoting biofilm formation and increasing meropenem tolerance

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• . Interfering with the interaction of the pathogen with its host in this way is believed to both reduce damage to the host and to enable the host to clear the microbe from its system. Furthermore, as antivirulence drugs do not kill, it is believed that the selection pressure for resistant mutants will be

• that, in addition to antimicrobial resistance, forms biofilms, a complex matrix of extracellular polysaccharides, polypeptides and DNA, which act as an additional protective barrier [30]. P. aeruginosa employs two lectins for biofilm formation and host–cell adhesion: proteins LecA and LecB [31][32

• of AB5 toxins. These Shiga toxins are the causative agents for bacterial virulence in the gut of the infected host and bind to the P blood group antigens that bear terminal Gal-α-1,4-Gal disaccharides. Blocking Stx1 with decavalent molecules STARFISH (20) and Stx1 and Stx2 with DAISY (21) resulted in

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• central regulator mechanism of virulence expression that contributes to the formation and maintenance of biofilms and tolerance to conventional antimicrobials. QS Signaling molecules (QSSMs) may be recognized and may function also within the host cells, being potentially involved in the progression of the

• infectious process. In this study we evaluate the expression of adhesion and inflammatory molecules in endothelial cells treated with P. aeruginosa QSSMs, in order to bring new insights on the mechanisms involved in the interaction of P. aeruginosa with host cells during the infectious process. Endothelial

• presence of all tested QSSMs. The adherence index of PAO1 laboratory strain to host cells was decreased between 10–40% in the presence of QSSMs, as compared to untreated control. Expression of eukaryotic cells adhesion molecules ICAM-1 and P-selectin was stimulated by QSSMs, whereas VE-cadherin and PECAM-1

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• integration of viral DNA into host cell chromatin (Figure 1) [7][8][9]. In contrast to the FDA approved integrase strand transfer inhibitors (INSTIs) dolutegravir, elvitegravir, and raltegravir, arylquinolines 1 and 2 bind to a non-catalytic site of integrase (NCINI) via allosteric binding inhibition

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• , geometries in all cases were optimized within the continuum solvation model (PCM) [31][32] of the DCM solvent, using the default solvent parameters as provided with Gaussian-09 Revision E.01 [33]. The results are summarized in Table 1 and Table 2. For the free OPC4A host molecule, initial geometry-optimized

• ambiguous DFT data than those of the halide salts in this study. As can be seen in structures d–f in Figure 3, there are more guest C–H(guest)–π(host) interactions possible as the size of the alkyl groups increase from groups Me < Et < n-Bu, which could also account for the observed trend in their binding

• constants. Conclusion Based upon the DFT calculations which we previously conducted in the solid-state study of 5 with C60, we postulated that due to the mechanochemical method of combining both components and the spherical nature of C60 that a possible interaction mode between host and guest could be as

Coordination-driven self-assembly of discrete Ru₆–Pt₆ prismatic cages

• Aderonke Ajibola Adeyemo and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2018, 14, 2242–2249, doi:10.3762/bjoc.14.199

• [47][48][49][50][51] and host–guest chemistry [52][53][54][55][56] among others. The cardinal prerequisites to obtain these self-assembled supramolecular architectures include stoichiometry and conformational complementarity on the binding sites of the building blocks [57][58][59][60][61]. However

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• = (2.29 ± 0.27) × 106 M−1) is 3.9 times larger than that of P (Ka = (5.87 ± 0.24) × 105 M−1). Keywords: berberine; biphenarenes; host–guest complexes; molecular recognition; palmatine; Introduction Host–guest chemistry in water is significantly important due to its extensive applications in biology

• specific structures and interesting host–guest properties [21][22][23][24][25][26][27][28][29][30][31][32]. Water-soluble pillar[n]arene derivatives, especially those containing carboxylato moieties, showed low cell toxicity and good biocompatibility, and have been applied in biomedical applications such

• as bioimaging and self-assembled drug delivery systems [33][34][35][36][37][38][39][40]. For example, our group demonstrated a direct host–guest complexation-based drug delivery system for oxaliplatin by carboxylatopillar[6]arene [36]. The encapsulation could not only improve the drug‘s stability in

A general and atom-efficient continuous-flow approach to prepare amines, amides and imines via reactive N-chloramines

• Katherine E. Jolley,
• Michael R. Chapman and
• A. John Blacker

Beilstein J. Org. Chem. 2018, 14, 2220–2228, doi:10.3762/bjoc.14.196

• is a facile route to imines, which may be used for further functionalization. Our study began by examining a host of bases to convert N-chloramine 5 to benzylidene(methyl)amine (19) as a model reaction system (Table 4). To achieve a complete conversion, NEt3 was required in large excess (5 equiv