Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• noteworthy renaissance not only because of the lower toxicity, stability, speed, and efficiency of the method, but also thanks to the easy generation of radical species and the formation of a long-lived triplet excited state under photoirradiation that can behave as a reductant as well as an oxidant [51][52

• catalysts, such as low toxicity, their functioning at room temperature, and smooth irradiation requirements with low-energy lights (e.g., LEDs, fluorescent bulbs, etc.) made this area of research very interesting. Within a very short time, photoredox catalysis has emerged as an important future direction

Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation

• Jucleiton J. R. Freitas,
• Queila P. S. B. Freitas,
• Silvia R. C. P. Andrade,
• Juliano C. R. Freitas,
• Roberta A. Oliveira and
• Paulo H. Menezes

Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19

• ] or boron [26][27][28] to perform propargylation reactions typically requires catalysis by Lewis acids or bases and although the utility of allenylstannanes is further indicated by the commercial availability of some of them, the toxicity of these compounds makes them inappropriate for the use in

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• maintain photostationary state equilibria in cellulo [10]. We cross-checked different illumination wavelengths in cellular toxicity assays; in accordance with the DMSO photoswitching studies, we observed that 530 nm (ca. 97% Z-configuration, but additionally controls for non-specific phototoxicity

• observed its photoswitching in pure aqueous media, in the heterogeneous cellular environment, we found that its overall toxicity under lit conditions was reliably and reproducibly halved. We then explored changes to the substituent pattern to determine whether we could improve both Z-isomer potency in an

• disruption. Lastly, to substantiate the causative link between the observations on MT disruption and cellular toxicity, we examined the impacts of HITub-4 on the cell cycle. Tubulin-binding agents whose major cellular mechanism of toxic action is the disruption of MT dynamics or structure should cause cell

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• intrinsic toxicity of the employed drugs [11][12][13]. As a result, there is an urgent need for DNA-targeting chemotherapeutic reagents that can be activated with an external stimulus only at the desired point of action. In this context, light offers several distinct advantages to switch on the activity of

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• rerio, and determined the toxicities of the peptides in terms of 50% lethal doses (LD50). This study allowed us to: (i) demonstrate the feasibility of evaluating peptide toxicity with D. rerio larvae at 3–4 days post fertilization, (ii) determine the phototherapeutic safety windows for all peptides

• , (iii) demonstrate photoswitching of the whole-body toxicity for the dithienylethene-modified peptides in vivo, (iv) re-analyze previous structure–toxicity relationship data, and (v) select promising candidates for potential clinical development. Keywords: diarylethene photoswitch; gramicidin S

• plasma stability in vivo, limited understanding of their mechanisms of action, and high in vivo toxicity. The former two drawbacks are being adequately resolved [9] (e.g., by modifying the peptide backbone [10], macrocyclization [11], or by use of unnatural amino acids [12]), and mechanistic

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• formation of Staphylococcus aureus DSM1104. The lack of toxicity toward the studied microorganism and cell lines of pigmentosin B (2), as well as the antimicrobial effect of pigmentosin A (1), made them good candidates for further development for use in combination therapy of infections involving biofilm

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• arylacetylenes [7][8] having great importance in organic synthetic schemes of the pharmaceutical industry. From the environmental point of view, the Sonogashira reactions are usually performed in fossil-based common organic reaction media having high vapor pressure even at higher temperatures, toxicity

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• component analysis [140], qPCR/proteomics [141], and iterative grid search [142] to troubleshoot and guide the tuning of the promoter strengths and copy numbers of each module/enzyme (Figure 11b). Toxicity of biosynthetic intermediates, endogenous regulation, and stability of genetic constructs are the main

• accumulation of FPP (Figure 11c) [143]. Alternatively, in vitro pathway reconstitution led to the successful production of several monoterpenes, circumnavigating toxicity to the heterologous hosts [144]. Several intermediates are also known to inhibit enzyme activities in the pathway. Novel pathways, such as

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• extremely harmful to environmental and biological systems [3]. In light of mercury’s toxicity, the synthetic community has given much attention to the use of less harmful reagents. Success has been obtained with many other transition metal salts, for example, palladium(II) [4][5], rhodium(III) [6], copper

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• ability to selectively accumulate in the target tissue, the absence of toxicity, toxic byproducts and mutagenic effects, and an opportunity for medical administration. An additional advantage of porphyrins is the possibility of functionalization of the macrocycle periphery with various substituents and

Synthesis of novel sulfide-based cyclic peptidomimetic analogues to solonamides

• José Brango-Vanegas,
• Luan A. Martinho,
• Lucinda J. Bessa,
• Andreanne G. Vasconcelos,
• Alexandra Plácido,
• Alex L. Pereira,
• José R. S. A. Leite and
• Angelo H. L. Machado

Beilstein J. Org. Chem. 2019, 15, 2544–2551, doi:10.3762/bjoc.15.247

• prevent the expression of Staphylococcus aureus virulence factors such as α-hemolysin and phenol-soluble modulins without affecting the bacterial growth [3]. Particularly, solonamide B and its analogues revealed no detectable toxicity against erythrocytes or human neutrophils [3][4]. Staphylococcus aureus

Synthesis of a dihalogenated pyridinyl silicon rhodamine for mitochondrial imaging by a halogen dance rearrangement

• Jessica Matthias,
• Thines Kanagasundaram,
• Klaus Kopka and
• Carsten S. Kramer

Beilstein J. Org. Chem. 2019, 15, 2333–2343, doi:10.3762/bjoc.15.226

• Information File 1, compare STED images with their corresponding confocal images. By resolving the tubular structure of mitochondria, we prove successful application of our mitochondria-selective pyridinyl SiR 15 in STED nanoscopy. Toxicity of the pyridinyl silicon rhodamine 15 Although for PET examinations

• precursor 15. For toxicity assessment, the frequency and duration of cell division with and without incubation with dye 15 was analyzed via time-lapse holographic imaging (Figure 3). U2OS cells were incubated with 1 µM dye 15 in medium for 1 h and, after washing with dye free medium, continually imaged over

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses

• Anne-Marie Caminade,
• Artem Zibarov,
• Eduardo Cueto Diaz,
• Aurélien Hameau,
• Maxime Klausen,
• Kathleen Moineau-Chane Ching,
• Jean-Pierre Majoral,
• Jean-Baptiste Verlhac,
• Olivier Mongin and
• Mireille Blanchard-Desce

Beilstein J. Org. Chem. 2019, 15, 2287–2303, doi:10.3762/bjoc.15.221

• (Figure 12). Studies of the TPA properties demonstrated that some of these dendrimers outperform the TPA cross-section response of quantum dots, while having a much lower intrinsic toxicity, as being composed or organic matter instead of heavy metals. The grafting of water-solubilizing functions on the

• deciphering mechanism of action of anticancer compounds, and recently for safer photodynamic therapy. In view of the results already obtained, there is no doubt that other biological properties of these fully organic “nanodots” can be foreseen, thanks to their low toxicity, large color modularity, and high

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• of these technologies has been partially hampered by the high cost and toxicity associated with Pd, in addition to the difficulty encountered when attempting to remove this metal from product mixtures. Therefore, cupper as low-cost, earth-abundant and readily available transition metal has emerged as

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• from Heydenia cf. alpina strain 824. Acknowledgements We are grateful to Tobias Meinert and Max Schirp Schönen (RWTH Aachen, Aachen, Germany) for 3D modeling of the FIND and to Tobias Benkel (University of Bonn, Bonn, Germany) for performing of the toxicity assays.

Naphthalene diimides with improved solubility for visible light photoredox catalysis

• Barbara Reiß and
• Hans-Achim Wagenknecht

Beilstein J. Org. Chem. 2019, 15, 2043–2051, doi:10.3762/bjoc.15.201

• photoredox catalytic behavior, transition metal complexes have disadvantages, including high costs due to limited availability, toxicity [22][23] and polluting properties [24]. This thwarts the principally “green” concept of photoredox catalysis. In order to avoid transition metals and enhance the

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• treatment of rheumatoid arthritis (RA) [31], systemic lupus erythematosus (SLE) and skin allograft rejection [32]. Despite the promising biological activities of triptolide, the narrow therapeutic window and multi-organ toxicity hindered greatly its clinical progress. Reports have shown that triptolide

• could cause reproductive toxicity [33], nephrotoxicity [34], hepatotoxicity [35], myocardial damage [36] and gastrointestinal tract symptoms [37]. In order to overcome the above issues and find derivatives with good drug-like properties, extensive total syntheses and structure modifications have been

Archangelolide: A sesquiterpene lactone with immunobiological potential from Laserpitium archangelica

• Silvie Rimpelová,
• Michal Jurášek,
• Lucie Peterková,
• Jiří Bejček,
• Vojtěch Spiwok,
• Miloš Majdl,
• Michal Jirásko,
• Miloš Buděšínský,
• Juraj Harmatha,
• Eva Kmoníčková,
• Pavel Drašar and
• Tomáš Ruml

Beilstein J. Org. Chem. 2019, 15, 1933–1944, doi:10.3762/bjoc.15.189

• micromolar range and up to the tested concentration of 50 µM, 50% cell death was only reached for HEK 293T and LNCaP after 72 h of treatment. Moreover, we also did not detect toxicity of compound 1 in primary and transformed cell lines. Based on these differences from thapsigargin and compound 2, it seems

• to 75% (statistically not significant) was also recorded when rat primary macrophages were incubated with 1000 pg·mL−1 LPS + 40 µM compound 5. However, no toxicity was observed for the combination of LPS + dansyl amide at the same concentration. Immunomodulatory [26] and anti-inflammatory [27

• , USA). The treated or untreated cells (DMSO as a vehicle) were cultured for 24 h and plates were maintained at 37 °C, 5% CO2, in a humidified Heraeus incubator. Stock solutions of compound 1 and 5 were prepared 100 mM in DMSO. For the cultivation of macrophages and assessment of toxicity and NO level

Morphology-tunable and pH-responsive supramolecular self-assemblies based on AB₂-type host–guest-conjugated amphiphilic molecules for controlled drug delivery

• Yang Bai,
• Cai-ping Liu,
• Di Chen,
• Long-hai Zhuo,
• Huai-tian Bu and
• Wei Tian

Beilstein J. Org. Chem. 2019, 15, 1925–1932, doi:10.3762/bjoc.15.188

• on the basis of the dissociation of host–guest interactions between β-CD and BM. Cellular toxicity of drug-loaded supramolecular self-assemblies The biocompatibility of drug-free supramolecular self-assemblies is of crucial importance for the further use of these materials as drug carriers. Herein

• 240 μg/mL, indicating a good biocompatibility. An MTT assay was then conducted to evaluate the potential of supramolecular self-assemblies as intelligent drug release carriers within a biological environment. The cellular toxicity of DOX-loaded FSSAs and free DOX·HCl against PC-3 cells was further

• acidic conditions into spherical supramolecular self-assemblies with smaller size. The morphology transitions can be utilized to realize a two-stage drug release. The uptake of the DOX-loaded supramolecular self-assemblies performed efficiently and the cellular toxicity through inhibiting cell

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• TLR2 receptor, whereas MDP lacks TLR2-agonistic activity [10]. PGM and MDP have similar immunostimulating activity and they are reduced in comparison to the potent complete Freund’s adjuvant which is used as golden standard for adjuvant activity [11]. However, strong toxicity of complete Freund’s

A golden opportunity: benzofuranone modifications of aurones and their influence on optical properties, toxicity, and potential as dyes

• Joza Schmitt and
• Scott T. Handy

Beilstein J. Org. Chem. 2019, 15, 1781–1785, doi:10.3762/bjoc.15.171

• . In this study, the influence of substitution in the benzofuranone ring on the UV–vis spectrum is explored, as well as an initial screening of their toxicity and a qualitative preliminary study of their potential to act as fabric dyes. Keywords: aurone; dyeing; dyes; substitution effect; toxicity; UV

• sake of high purity, so yields should not be considered optimized. Spectral and toxicity studies With the desired compounds in hand, their UV–visible spectra were recorded at concentrations between 29 and 44 μM in acetonitrile (Figure 3 and Table 1). While not all substituents were prepared at every

• definitely increase this value by roughly 50%). While these results on the impact of the benzofuranone portion of aurones on their optical properties are interesting, if one were to think about using them as dyes, toxicity is also an important consideration. Generally, aurones are considered to be relatively

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

• Quentin Huaulmé,
• Cyril Aumaitre,
• Outi Vilhelmiina Kontkanen,
• David Beljonne,
• Alexandra Sutter,
• Gilles Ulrich,
• Renaud Demadrille and
• Nicolas Leclerc

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

• ] but these molecules reveal low absorption coefficients over the visible range. Furthermore, they contain a rare and a relatively high-cost element (Ru) and their plausible toxicity restrains their development at the industrial level. For these reasons, in the last decade, metal-free organic dyes based

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• in toxicity and fits to the tenets of green chemistry. Zinc in the form of its salts, complexes (chelated by mono/di/tri/tetradentate ligands), oxides and sulfides proved to be a promising and active catalyst for organic chemists in both homogeneous as well as heterogeneous reaction systems [23][59

• systems based on zinc with excellent activity has been designed and used. The role of iron in synthetic chemistry Iron being the most abundant heavy element on earth with low biological toxicity along with cost economy and high reactivity was explored by Kharasch and Fields in the 1940s and Tamura and

Synthesis and biological evaluation of truncated derivatives of abyssomicin C as antibacterial agents

• Leticia Monjas,
• Peter Fodran,
• Johanna Kollback,
• Carlo Cassani,
• Thomas Olsson,
• Maja Genheden,
• D. G. Joakim Larsson and
• Carl-Johan Wallentin

Beilstein J. Org. Chem. 2019, 15, 1468–1474, doi:10.3762/bjoc.15.147

• core structure, 1 only has one stereocenter as compared to seven in AbC. Furthermore, the benzylated derivative 2 was also envisioned to mimic the favorable toxicity profile observed for atrop-O-benzyl-desmethyl-abyssomicin C (Figure 1) [10]. Here we present the synthesis and biological evaluation of 1

• , no further investigations related to the conserved mode of action or toxicity were performed. Conclusion We have described the synthesis and antibacterial activity of two new truncated derivatives of AbC. Previous work indicated that the three methyl groups of AbC were not required for activity [10

Reversible end-to-end assembly of selectively functionalized gold nanorods by light-responsive arylazopyrazole–cyclodextrin interaction

• Maximilian Niehues,
• Patricia Tegeder and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2019, 15, 1407–1415, doi:10.3762/bjoc.15.140

• the complete surface because of its cell toxicity [17], hence strategies for replacing this coating are desirable. Host–guest chemistry is a supramolecular interaction that is tailor-made for self-assembly due to its lock–key mechanism and has been applied in our and other groups to various