Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• biomolecules like DNA and lipids. Lipid peroxidation and membrane disruption can cause random cross-linking, resulting in cell death and the fragmentation of proteins and enzymes. Elevated concentrations of reactive oxygen species (ROS) from various molecular processes contribute to the oxidation of proteins

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• of action (MOA) (e.g., membrane lysis and depolarization) [30][34] and specific MOA (e.g., dysregulation of ClpP protease [33], inhibition of topoisomerase I/II [36][68], blocking lipid II transport by flippase [29], sequestration of cell wall biosynthetic intermediate C55-(di)phosphate, etc.) [35

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• represent promising candidates for drug discovery, because of their improved water solubility, membrane permeability, and improved recognition by the respective receptors [16]. The present article aims to provide an updated review of the chemistry and biological applications of N-glycosides of indigo

• anticipated that PAM activates channels of the membrane of melanoma cells to allow the antiproliferative compound (β-33b) to enter the cell. Thus, β-33b combined with PAM might be developed to a new and promising method of therapeutic intervention. This concept of combination of PAM with drugs could also be

• negative feed-back loop by TRAIL and an upregulation of both receptors. In addition, a loss of mitochondrial membrane potential and release of cytochrome c was observed which gave rise to an activation of intrinsic apoptosis pathways. The mitochondrial response seems to be related to an upregulation of Bax

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• /ERG11 gene. This enzyme contains a haem-like prosthetic group in its active center and is a member of the cytochrome P450 family, which plays a key role in the biosynthesis of sterols. Sterols in turn are integral components of the fungal cell membrane, making inhibition of CYP51 [43] an effective

Interaction of a pyrene derivative with cationic [60]fullerene in phospholipid membranes and its effects on photodynamic actions

• Hayato Takagi,
• Çetin Çelik,
• Ryosuke Fukuda,
• Qi Guo,
• Tomohiro Higashino,
• Hiroshi Imahori,
• Yoko Yamakoshi and
• Tatsuya Murakami

Beilstein J. Org. Chem. 2024, 20, 2732–2738, doi:10.3762/bjoc.20.231

• membrane potential (Vm) in living cells. These previous studies indicated that the localization of the triad molecules in a specific intra-membrane orientation and the suppression of the photodynamic actions of the [60]fullerene (C60) moiety are likely important to achieve fast and safe control of Vm

• an acceptor in photoinduced charge-separation systems, we have previously employed ferrocene-porphyrin-C60 triad molecules (Figure 1a) in a biological system to control the plasma membrane potential (Vm) of living mammalian neuronal cells under photoirradiation [4][5][6]. Generally, Vm originates

• from a difference in electric charge on the two sides of the plasma membrane (approximately 5 nm thickness), with a slight excess of the positive ions inside relative to the negative ions outside. Our ferrocene-porphyrin-C60 triad molecule exhibited long-lived charge-separated states under visible

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• ][3][4][5][6][7]. What about other halogens? Pyran inter-halide analogues of carbohydrates were rarely investigated as new tools in glycobiology [8]. This is surprising since the incorporation of halogens can improve cellular uptakes and enhance membrane binding and permeation [9][10][11]. In addition

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• constituting glycoproteins or glycolipids, respectively. Recently, glycan structures exposed on the cellular membrane have also been found to be associated with tRNA [2]. In other species, such as prokaryotes, plants or fungi, glycoconjugates comprise the cell wall, playing critical metabolic, structural and

• platform contains a number of different modules designed to construct complex glycans, glycoconjugates as lipopolysaccharides (LPS), or even building a membrane system or solvating a protein. To use all these features, grouped in the Input Generator tab (https://www.charmm-gui.org/), it is necessary to be

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• second generation series, i.e., compounds 91–94 (Scheme 12), featuring simple hydrocarbon substituents was elaborated. This collection showed good activities, demonstrating the tolerance of introducing bulky moieties at position C2 or N1 of the imidazole ring. Researchers also described positive membrane

• originally synthesized by Palazzo et al. [76] and several other derivatives were developed based on ethylamine-chain homologation [77]. Triazoles: Hall and co-workers [78] developed 1,2,3-triazolyl analogues 111 of ʟ-histidine for ʟ-type amino acid transporter 1 (LAT1) activity, a sodium-independent membrane

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• catalyze the formation of Dha-Cys or Dhb-Cys [21]. Moreover, lanPt encodes a membrane protein with two ABC transporter domains and a C39 peptidase domain. The protein cleaves the leader peptide to generate mature lanthipeptides and exports them to the extracellular environment [22]. The diversity of

• in more pronounced morphological changes after 5 hours of treatment. The changes included the loss of the characteristic cocci structure, with the formation of blebs that increased the membrane's rugosity. Besides, cytosolic leakage and remnants of the outer membrane were identified (see Figure 6B, C

• , G, and H). The treatment with the mature peptides led to numerous blebs visible after 1 hour. Interestingly, no cocci structures were detected after 5 hours of treatment (see Figure 6). The precursor peptides, especially cellulosin, appear to elicit some effects on the membrane of S. epidermidis

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• oxidation of phenols on A- and E-rings, yield bisquinone 94. The membrane-bound peptidase SfmE excises the long-chain fatty acid moiety on the N-terminus of the C1 side chain. Secretion through the efflux pump SfmG, and extracellular oxidative deamination catalyzed by the berberine bridge enzyme (BBE)-like

• fatty acid moiety on the C1 side chain (Scheme 9). Although the enzymatic deacylation of 94 can be catalyzed by the membrane-bound peptidase SfmE, similar chemical transformations require harsh conditions and are difficult to perform in the presence of highly reactive functional groups. To circumvent

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• perform oxygen-directed methylation [59]. A range of natural products are known to undergo O-methylation [61], improving membrane permeability, absorption, and oral bioavailability [61][62]. The most extensively studied O-MTs are those that methylate catecholic hydroxy groups [63]. Several O-methylation

• proteusin family of RiPPs. They are produced by the tunicate symbiont Candidatus Entotheonella factor and exhibit membrane activity against Gram-positive bacteria and are highly cytotoxic. Cytotoxicity was tested with murine leukaemia cells; polytheonamide A, B, and C showed IC50 values between 68 and 78 pg

• towards the C-terminus, named "axial amphipathicity". Thus, this methylation is thought to play an important role in correct target membrane insertion and the associated cytotoxic effect [125]. TsrM is another cob(II)alamin-dependent C-MT (Figure 10). This enzyme is involved in the biosynthesis of

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• applications and performances depend on key components such as their separators/ion-exchange membranes. The most studied and already commercialized Nafion membrane shows great chemical stability, but its water content limits its high proton conduction to a limited range of operating temperatures. Here, we

• -triazinephosphonate (TPs) derivatives. The evaluation of the proton conduction properties of the new membranes and relative humidity (RH) conditions and at 60 °C, showed that they present higher proton conductivities than the prepared Nafion membrane and similar or better proton conductivities than commercial Nafion

• N115, in the same experimental conditions. The Nafion-doped membrane with compound TP2 with a 1.0 wt % loading showed the highest proton conductivity with 84 mS·cm−1. Keywords: electrolyser; fuel cells; Nafion-modified membranes; phosphonates; proton exchange membranes; triazine; Introduction

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• found in nature in order to enable different biological functions in a precise manner, e.g., actin in biological molecular motors, the cytoskeleton, and cell membrane [5][6][7][8]. Mimicking natural supramolecular assemblies in aqueous medium, the intrinsic supramolecular dynamicity, stimuli

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• cyanoarenes, nitroarenes, quinolines, and pyridines using a proton-exchange membrane (PEM) reactor was developed. Cyanoarenes were then reduced to the corresponding benzylamines at room temperature in the presence of ethyl phosphate. The reduction of nitroarenes proceeded at room temperature, and a variety of

• hydrogen [13][14][15][16][17][18]. Meanwhile, electrochemical systems using solid polymer electrolytes (SPEs) have recently attracted significant attention [19]. Among these, proton-exchange membrane (PEM) reactors are powerful tools for hydrogenation [20][21][22][23][24][25][26][27][28][29][30][31][32][33

• ][34][35][36][37][38][39][40][41][42][43]. The PEM reactor included a membrane electrode assembly (MEA) consisting of a PEM and an electro-catalyst supported on carbon (Figure 1). Humidified hydrogen gas (H2) or H2O was injected into the anodic chamber and the substrate passed through the cathodic

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• obtained by centrifugation at 50400g for 16 h and subjected to UV−vis−NIR measurements (Figure 3a). After concentrating the extract obtained above, the residue (e-SWNTs) was suspended in dichloromethane by sonication and filtered through a PTFE membrane (pore size 0.1 μm). This washing process was repeated

• PTFE membrane. This process to remove host molecules was repeated three times, until no absorption bands from the host molecules were observed in the UV−vis spectra of washings. After the resulting p-SWNTs were washed with dichloromethane several times to thoroughly remove all the organic molecules

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• several significant processes, terpenoids play an indispensable role in cell-wall and membrane biosynthesis, sensing, plant defense, electron transport, or conversion of light into chemical energy [1][2]. Based on the number of hydrocarbon units, terpenes are classified into various families like

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• living organisms produce and use such metabolites as biocatalysts in nature. Therefore, it is thought that the production of HSMs has some physiological significance. For example, other microbial species reportedly activate energy metabolism and strengthen the cell membrane or walls in high-temperature

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• brevis [27], can penetrate the lipid phase of a Gram-positive inner cell membrane [28][29]. Despite exhibiting high antimicrobial activity, this compound also disrupts the membranes of higher mammalian cells, as evidenced by their pronounced hemolytic activity [30]. Establishing a concise and diverse

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• transporters to form the siderophore Fe(III) complex extracellularly [2][3]. Subsequently, the stable and water soluble siderophore Fe(III) complex is transported across the cell membrane into the cytoplasm, where the iron is released from the complex by reduction, generating free Fe(II) ions that are

• ) resembles those of other amphiphilic marine siderophores such as marinobactins and aquachelins exhibiting the membrane affinity [21] as well as the self-assembling ability to form iron-containing vesicles [22]. This study presents another suite of amphiphilic peptidic siderophores originating in the

• hydrolysates were dissolved in water (160 µL), and treated with saturated NaHCO3 (200 µL) and 1% ʟ-FDLA in acetone (160 µL). The mixtures were heated at 40 °C for 30 minutes, quenched with 1 M HCl (200 µL), and concentrated in vacuo. The residue was dissolved in DMSO (400 µL) and passed through a membrane

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• cyclizations and post-cyclization modifications are especially important in fungal meroterpenoid biosynthesis, contributing to the structural diversity of this class of compounds. Fungal meroterpenoid cyclases (CYCs) are seven-membrane-spanning transporter-like enzymes that regulate the conformations of

• chair–chair stereocontrol, the structure basis of InsA7 should be unique. A structural comparison of InsB2 and InsA7 will help to clarify the differences in their structural bases. Recent advances in artifical intelligence (AI) have even made the structural modeling of membrane-bound proteins possible

• have also expanded the variety of meroterpenoids [41][42]. These untapped membrane enzymes will be applicable for engineered biosynthesis, with structural models providing useful information for mutagenesis, as in the engineering of meroterpenoid cyclases [11] and fungal P450 oxygenases catalyzing

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• represents prototypes of molecular machines in which guest binding is regulated by stimuli-induced conformational changes between open and closed states (Figure 1). This feature holds significant promise for applications in sensing, drug delivery, or membrane transport within biological systems. Moreover

• release of siRNA or miRNA encapsulated within them into the solution in vitro and in vivo [21]. The closed conformation of 2 with parallel alkyl chains acts as a building block of the bilayer membrane and is packed together with other lipids. When the surrounding medium becomes acidic, the tweezers adopt

• their open conformation. This causes fluctuations and local defects in the packing of a bilayer (Figure 3), leading to membrane disruption and release of active components from within the vesicles [22]. Such concept makes these tweezers good candidates for controlled drug delivery. The group of F. Wang

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• is synthesized on the inner leaflet of the cytoplasmic membrane, before translocation to the outer leaflet, where it is then used as the monomeric building block of peptidoglycan biosynthesis. Lipid II is a validated antibiotic target for clinically prescribed antibiotics including vancomycin and

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• and at the same time improved cell membrane permeability. Therefore, it became a commonly used strategy to modify medicine candidates [22][23][24]. Based on these advantages, we envisioned a one-step synthesis of dihydropyrido[1,2-a]indolone skeletons utilizing an indole substrate and a

Preparing a liquid crystalline dispersion of carbon nanotubes with high aspect ratio

• Keiko Kojima,
• Nodoka Kosugi,
• Hirokuni Jintoku,
• Kazufumi Kobashi and
• Toshiya Okazaki

Beilstein J. Org. Chem. 2024, 20, 52–58, doi:10.3762/bjoc.20.7

• 200 mL of water, the DWCNT-glycerol mixture was filtered through a 1.0 μm pore size polytetrafluoroethylene (PTFE) membrane (Merck, Omnipore 47mm). To ensure complete removal of glycerol from the DWCNTs, we repeated the washing process until 2 L of water had passed through the membrane, resulting in