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

Total synthesis of decarboxyaltenusin

• Lucas Warmuth,
• Aaron Weiß,
• Marco Reinhardt,
• Anna Meschkov,
• Ute Schepers and
• Joachim Podlech

Beilstein J. Org. Chem. 2021, 17, 224–228, doi:10.3762/bjoc.17.22

• agreement with the NMR data measured by us, what leaves no reasonable doubt that the synthesized structure 1 is identical with the natural product. Decarboxyaltenusin (1) was screened for toxicity towards human HeLa cells but proved nontoxic at biologically relevant concentrations and showed an LD50 value

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• times if compared with toluene. We therefore selected CPME as the most suitable solvent for our purposes. Interestingly, besides being characterized by low toxicity, CPME has a very low affinity to water, making it suitable for moisture sensitive reactions, without previous distillation [31][32][33

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• as an early warning signal to the attacker. The fluid toxicity and bitterness, added to the characteristic odor of these insects, have been regarded as a protection against insect or vertebrate predators [3]. Bicyclic ring systems bearing a nitrogen bridge are often found in nature [4][5][6]. Typical

• concentration of coccineline found in C. septempunctata [31]. This difference may occur to compensate (−)-adaline's lower toxicity than coccineline. Biosynthetic studies carried out by Laurent et al. [33][34] showed that adults of A. bipunctata incubated in vitro with [14,14,14-3H3]myristic acid incorporated

Chemical constituents of Chaenomeles sinensis twigs and their biological activity

• Joon Min Cha,
• Dong Hyun Kim,
• Lalita Subedi,
• Zahra Khan,
• Sang Un Choi,
• Sun Yeou Kim and
• Chung Sub Kim

Beilstein J. Org. Chem. 2020, 16, 3078–3085, doi:10.3762/bjoc.16.257

• (betulinic acid) and 8 (apigenin) also exhibited significant activity with IC50 values of 4.3 and 16.6 μM, respectively. Tolstikov et al. reported that betulin (9) and its derivatives showed antiviral and antitumor effects [41]. Interestingly, betulinal (11) has an advantage in view of toxicity as compared

• compounds, only compound 8 (apigenin) exhibited a weak activity on the NGF release with a stimulation level of 127.8 ± 2.0% without displaying cell toxicity (100.9 ± 0.6%). Conclusion A new megastigmane-type norsesquiterpenoid glycoside 1 was isolated along with 11 known compounds from the MeOH extract of C

Metal-free nucleophilic trifluoromethylselenolation via an iodide-mediated umpolung reactivity of trifluoromethylselenotoluenesulfonate

• Kevin Grollier,
• Alexis Taponard,
• Arnaud De Zordo-Banliat,
• Emmanuel Magnier and
• Thierry Billard

Beilstein J. Org. Chem. 2020, 16, 3032–3037, doi:10.3762/bjoc.16.252

• particular by combining heteroatoms, such as chalcogens, and fluorinated moieties [16]. Despite, the negative reputation of selenium due to its toxicity at high doses, it is an essential trace element for human physiology and biochemistry [17][18][19][20]. Furthermore, selenolated compounds found valuable

Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives

• Emese Gal,
• Luiza Gaina,
• Hermina Petkes,
• Alexandra Pop,
• Castelia Cristea,
• Gabriel Barta,
• Dan Cristian Vodnar and
• Luminiţa Silaghi-Dumitrescu

Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242

• toxicity effects are predictable for the new compounds 2c, 2i, and 2l at concentrations ranging at their solubility maxima. The possible antimutagenic effect of the selected C-substituted α-aminoacetonitriles 2c, 2i, and 2l, respectively, in the presence of 2-aminoantracene, daunomycin (mutagens for TA 98

A proposed sustainability index for synthesis plans based on input provenance and output fate: application to academic and industrial synthesis plans for vanillin as a case study

• John Andraos

Beilstein J. Org. Chem. 2020, 16, 2346–2362, doi:10.3762/bjoc.16.196

• solvent i is given by Equation 15. where the metric parameters (M) cover occupational exposure limit (OEL, ppm), LD50 (ingestion toxicity, mg/kg), LC50 (inhalation toxicity, g m−3 for 4 h), global warming potential (GWP, unitless), smog formation potential (SFP, unitless), ozone depletion potential (ODP

• , unitless), acidity-basicity potential (ABP, unitless), bioconcentration potential (BCP, unitless), persistence potential (PER, unitless), soil sorption coefficient (soil, Koc), half-life of solvent in environment (half-life, h), aquatic toxicity to fish (aqua, mg/L for 96 h), Q-phrase potential (Q-phrase

Host–guest interaction of cucurbit[8]uril with oroxin A and its effect on the properties of oroxin A

• Zhishu Zeng,
• Jun Xie,
• Guangyan Luo,
• Zhu Tao and
• Qianjun Zhang

Beilstein J. Org. Chem. 2020, 16, 2332–2337, doi:10.3762/bjoc.16.194

• involve three main intermolecular forces: a hydrophobic effect, hydrogen bonding and ion–dipole interactions at the carbonyl portals [7][8][9]. The high thermal stability [10], ease of synthesis [11], general absence of cytotoxicity or toxicity [12][13] and their good molecular recognition and binding

• [21], can help to reduce the side effects and toxicity of the drug [22]. Oroxin A (OA, baicalein-7-O-glucoside, Figure 1A) is one of the active ingredients isolated from the traditional herbal medicine Oroxylum indicum (L.) Kurz of Asian countries [23][24]. Accumulating studies have shown the

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• )-ones. A selective synthetic approach to 2-hydroxy-2H-1,4-benzothiazin-3(4H)-ones was developed via the solvent-switchable reaction of furan-2,3-diones with o-aminothiophenol. Preliminary biological assays (antimicrobial, acute toxicity) of the new compounds were carried out. Keywords: acylpyruvic acid

• , inducing its attack on the carbonyl group bearing a higher partially positive charge (for partial charges comparison, see Supporting Information File 1). As we were most interested in the biological activity of BTAs 3, preliminary antimicrobial and toxicity assays of these compounds were carried out

• albicans, Cryptococcus neoformans var. grubii, Mycobacterium tuberculosis) in vitro. Acute toxicity of BTA 3a in mice was determined to be higher than 1000 mg/kg, which means that BTA 3a can be considered as low toxic. Conclusion In conclusion, we developed two interchangeable approaches to enaminones

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• arylation of the nucleophilic nitrogen atom, known as the Ullmann [6][7] reaction, and its modification by Chan and Lam [8] are favored due to the several advantages they offer versus the Pd counterpart (i.e., the Buchwald–Hartwig reaction) such as the lower cost and lower toxicity of the metal as well as

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• properties of BODIPY and the biocompatibility of dextran. The BODIPY dextran nanoparticles were characterized regarding their size, morphology, polarity, and toxicity in vitro. We demonstrate the feasibility of mechanochemistry for boronic ester formation [23] to a glycan polymer as a route of conjugation

• also performed an MTT assay of the conjugate Dex-1b to evaluate its toxicity and we could observe basically no effect on cell proliferation in the A549 cell line (see Figure S6 in Supporting Information File 1), which remained above of 60% after 24 hours of incubation over the whole concentration range

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• speculated to raise toxicity issues [15]. Despite their similar size to hydrogen atoms, fluorine atoms possess a very different chemical reactivity and exert very different influences on neighboring atoms. C–H/C–F substitution in organic molecules influences practically all physical, pharmacokinetic

• liability for phospholipidosis [20], iii) an increased membrane permeability [21] and iv) the mitigation of undesired binding to the human ether a-go-go-related gene (hERG) K+ channel associated with cardiovascular toxicity [22]. Moreover, the radiochemical properties of the 18F nucleus render them crucial

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• ; thiol-mediated uptake; Introduction The effective delivery of substrates of free choice into cells with minimal endosomal capture on the one hand and a minimal toxicity on the other remains one of the grand challenges in science [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. This

• transfected with a plasmid expressing a fusion protein of HaloTag–GFP–Golgi localization sequence [63]. The HaloTags installed in the Golgi were then labeled with the reporter 26. Under these more challenging conditions, obvious problems arose from the toxicity of the transfecting agent, over- and

• (yellow areas only in Figure 7a). a) Automated HC imaging of the cellular uptake of 25, covering the concentration dependence for the HC CAPA with the cell body mask (blue), the HC CAPA with the mitochondrial mask (yellow), and the toxicity defined as the percentage of damage-free cells selected for the

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• strong immunostimulator and therefore a valuable target for the development of novel immunomodulators. Various lipid A derivatives have been chemically synthesized in order to reduce toxicity while retaining the immunostimulatory activity. In this work, we describe a novel approach to the frequently

• (structure 1, Figure 1). It was found that lipid X retained some immunomodulatory activity while having drastically reduced toxicity [10][11]. Lipid X was also found to give partial protection against a 100% lethal dose of endotoxin in mice [11]. However, there were also studies with conflicting results that

Three new O-isocrotonyl-3-hydroxybutyric acid congeners produced by a sea anemone-derived marine bacterium of the genus Vibrio

• Dandan Li,
• Enjuro Harunari,
• Tao Zhou,
• Naoya Oku and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1869–1874, doi:10.3762/bjoc.16.154

• pathogenic Vibrio species, suggesting the application of PHAs as a biocontrol agent [18]. Although the toxicity of 1–4 toward the producing strain was not tested, they weakly inhibited the growth of Tenacibaculum maritimum, a causative agent of skin ulcers in marine fish, at MIC values of 25 (1), 50 (2), 50

One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: theoretical evidence for an asynchronous concerted pathway

• Esra Demir,
• Ozlem Sari,
• Yasin Çetinkaya,
• Ufuk Atmaca,
• Safiye Sağ Erdem and
• Murat Çelik

Beilstein J. Org. Chem. 2020, 16, 1805–1819, doi:10.3762/bjoc.16.148

• pharmaceutical products [15]. Moreover, they are used as electrolyte components in Li-ion rechargeable cells and as aprotic polar solvent with high boiling point as alternative of dangerous solvents because of their good biodegradability and low toxicity [16][17][18]. Synthetic intermediates for ring-opening

Clickable azide-functionalized bromoarylaldehydes – synthesis and photophysical characterization

• Dominik Göbel,
• Marius Friedrich,
• Enno Lork and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2020, 16, 1683–1692, doi:10.3762/bjoc.16.139

• inert conditions [28] are necessary to facilitate an afterglow emission. Most phosphorescence studies are focused on metal complexes due to a strong heavy atom-induced spin-orbit coupling [29][30][31][32][33]. Considering the high price and the toxicity of many metal complexes, pure organic phosphors

Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• C(sp3)–C(sp3) bond-forming reactions [16][17], and closely resembles one of the very few biological blueprints for the preparation of fluorine-containing materials [18][19][20][21]. However, in translating the fluoroacetate-like building blocks to a laboratory paradigm, the intrinsic toxicity of

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• , wide electrochemical redox potentials, and photostability. However, these photocatalysts present serious drawbacks, such as toxicity, limited availability, and the overall cost of rare transition metal elements. This reduces their long-term viability, especially at an industrial scale. Heterogeneous

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• immunity [33], among which redox enzymes and antioxidants are the direct countermeasures to neutralize the toxicity of ROS [34]. Limited examples of antioxidants include catecholamine melanin from a fungus Cryptococcus neoformans [35], 1,8-dihydroxynaphthalene melanin from fungi Wangiella dermatitidis and

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• % edema inhibition) on a TPA topical model. Next, to assess the acute toxicity of the synthesized derivatives, test animals were administered with 50–100 mg/kg of 3–6, respectively, by an oral route, and after 14 days, neither lethality nor a significative weight loss were observed. Finally, a structure

• describe the enzyme inhibitor site binding modes [16][17][18]. Thus, in this work, the bisphosphonates 3–6 were synthesized by a two-step method and then evaluated through two in vivo acute inflammation models in BALB/c mice. Furthermore, the acute toxicity was determined for these derivatives, and

• antiinflammatory activity evaluation of the bisphosphonic esters 1 and 2, observing activity by oral (carrageenan model) and topical administration (TPA model) in BALB/c mice (Figure 1) [19]. Furthermore, in the search of more potent and low-toxicity derivatives, in this work, we have focussed our attention on the

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• states with different classes of molecules. However, the relatively high cost of these photocatalysts, their toxicity, and the limited abundance of the coordinating transition metals can hamper their applicability [13]. For these reasons, the quest for cheaper, more sustainable, and environmentally

Development of fluorinated benzils and bisbenzils as room-temperature phosphorescent molecules

• Shigeyuki Yamada,
• Takuya Higashida,
• Yizhou Wang,
• Masato Morita,
• Takuya Hosokai,
• Kaveendra Maduwantha,
• Kaveenga Rasika Koswattage and
• Tsutomu Konno

Beilstein J. Org. Chem. 2020, 16, 1154–1162, doi:10.3762/bjoc.16.102

• (e.g., Ru [14], Ir [15][16], Pt [17], and Au [18][19][20][21]) (Figure 1A), and this offers a molecular design approach for phosphorescence emission. However, it is becoming necessary to explore alternatives to rare metals because of the latter’s scarcity and toxicity. Owing to recent considerable

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• heterogeneous systems contained: PdO/Co3O4 with K2CO3 [33], MCM-41-S-PdCl2 [34], and MCM-41-2P-PdCl2 [35]. However, the aforementioned systems often suffer from high toxicity of solvents, high pressure of gases or high reaction temperatures, which make these protocols inapplicable for large scale applications