Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• embryonic cells. Identification of the cause of the registered selective toxicity of the tested compounds requires further study. Conclusion Thus, we have introduced an effective base-catalyzed tandem reaction including a Cornforth-type rearrangement of 1-heteroaryl-1,2,3-triazole-4-carboximidamides and

1-Butyl-3-methylimidazolium tetrafluoroborate as suitable solvent for BF₃: the case of alkyne hydration. Chemistry vs electrochemistry

• Marta David,
• Elisa Galli,
• Richard C. D. Brown,
• Marta Feroci,
• Fabrizio Vetica and
• Martina Bortolami

Beilstein J. Org. Chem. 2023, 19, 1966–1981, doi:10.3762/bjoc.19.147

• 1881, Kucherov identified mercury(II) salts in sulfuric acid as efficient promoters of the hydration of alkynes and this catalyst system has found applications in industrial scale synthesis [10]. However, the toxicity and the environmental issues associated with the use of mercury-based compounds have

• ][52][53][54]. However, some of these procedures suffer from major drawbacks, such as the toxicity and/or high cost of the metal catalysts, the need to use concentrated Brønsted acids in high excess, long reaction times, and high temperatures. In addition, these reactions have been studied mainly in

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• radical reactions. These reactions have garnered much attention due to their cost-effectiveness, low toxicity, and widespread availability. Notably, the NaI/PPh3 combined system has been successfully employed in the photofixation of nitrogen [51]. Despite these remarkable progresses made, there remain

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• ]. The study also found that those coordination compounds were selective towards abnormal cells, exhibiting lower toxicity for healthy human hepatocytes. On the other hand, an important development in cancer research is the use of physiological metal ion complexes, which afford more biocompatibility and

• ions. For this reason, we feel quite comfortable to state that these compounds are promising, and deserve deeper studies regarding their interactions with, for example, aluminum(III) and cell toxicity assessments. Experimental All solvents and reagents were purchased from commercial suppliers Sigma

A series of perylene diimide cathode interlayer materials for green solvent processing in conventional organic photovoltaics

• Kathryn M. Wolfe,
• Shahidul Alam,
• Eva German,
• Fahad N. Alduayji,
• Maryam Alqurashi,
• Frédéric Laquai and
• Gregory C. Welch

Beilstein J. Org. Chem. 2023, 19, 1620–1629, doi:10.3762/bjoc.19.119

• considered green, where a green solvent can be described as one that exhibits little to no toxicity to humans or animals, and has a minimal environmental impact when considering life-cycle assessments [21]. In terms of the electrochemical properties of the series, it was hypothesized that the addition of a

• are coated onto of the BHJ in this case [19]. Furthermore, ethyl acetate is considered a green solvent due to its low toxicity and minimal associated hazards [20][22][29]. We note that each compound has minimal solubility in methanol, the most common processing solvent for CILs, and instead encourage

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• cereals [31]. The isolation of the alternariol compound in this study is not surprising because it has been reported that dibenzo-α-pyrones are also found in mycobionts, plants, some animal dung, and endophytes [32][33]. Although the toxicity of dibenzo-α-pyrones is not fully understood and varies amongst

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• has similar cell toxicity than edelfosine-C18 on HL-60 leukemic cells [129][130]. The authors also reported that the sulfone 26.5 (Figure 26B) had similar cytotoxicity than edelfosine-C18. In 1987, the group of E. J. Modest reported that the thioether 26.4 featured comparable cytotoxicity than C18

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• , and the cleavage of the C(sp3)–H bond in the ether substrates which produces α-alkyl radicals is the rate-determining step. Fe-catalyzed reactions Iron is a transition metal with abundant reserves, low price, and non-toxicity, which shows many characteristics in catalytic processes, such as the

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• visible and near IR regions [11][12][13][14]. Similarly, simple quinoxaline-based heterocycles have shown their potential as photosensitizers to induce toxicity in a single cell green algae such as Chlamydomonas reinhardtii [15] and also displayed efficacy against Mycobacterium tuberculosis and other

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• presence of 4 mol % ZrOCl2∙8H2O as a catalyst in water at 60 °C (Scheme 11a). Among many catalysts used for the synthesis of N-substituted pyrroles, Zr(IV) compounds, especially ZrOCl2∙8H2O have received more attention because of its high coordination ability, low toxicity, low cost and high activity. In

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• their biodegradability [4], negligible toxicity, and excellent safety profile [5]. In addition, CDs offer a further step towards sustainability, making them suitable for a wide range of uses in various fields. Accordingly, the global market size of CDs is expected to grow to nearly US$ 390 million by

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• + T cells was investigated at corresponding concentrations of compounds 2–5. Regrettably, no enhancement of CD8+ T cells was observed (Figure S43 in Supporting Information File 1). To examine the toxicity of compounds 1–5, 7, and 8, the CCK-8 assay was employed to detect the viability of RAW264.7

• cells. The results indicate that the compounds did not exhibit significant toxicity toward RAW264.7 cells at the utilized concentrations (Figure 4A and B). Meanwhile, compounds 1‒5, 7, and 8 were evaluated for their anti-inflammatory activity against pro-inflammatory expression of iNOS and COX-2. The

Honeycomb reactor: a promising device for streamlining aerobic oxidation under continuous-flow conditions

• Masahiro Hosoya,
• Yusuke Saito and
• Yousuke Horiuchi

Beilstein J. Org. Chem. 2023, 19, 752–763, doi:10.3762/bjoc.19.55

• . From the viewpoint of application to pharmaceutical manufacturing, the residual amount of copper must be controlled according to ICH Q3D [41]. Iron and zinc have low toxicity and are not listed in ICH Q3D. In comparison with the initial reaction rate of 60 min, Fe(NO3)3/TEMPO in Table 1, entry 3 shows

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• on noble metal complexes has been constantly declined over recent years due to cost, availability, and toxicity, therefore discouraged by the modern guidelines towards implementation of sustainable chemical production schemes [6]. In the last decades, organic photochemistry has become a prominent

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• for catalysis, due to the generally higher abundance and lower toxicity of these elements. Group 13 elements have a rich catalogue of stoichiometric addition reactions to unsaturated bonds but cannot undergo the redox chemistry which underpins transition-metal catalysis. Group 13 exchange reactions

• after In‒N/B‒H exchange with HBpin gave a borylimine iron complex 110. A second hydroelementation and In‒N/B‒H exchange gave the bisborylamine 113 and regenerated the HInCl2 107 co-catalyst (Scheme 27). Conclusion Increasing concerns over the sustainability and toxicity of many transition-metal

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• and non-toxicity. However, partial hydrolysis of the p-toluenesulfonyl group takes place, so the final product is always contaminated with native β-CD (1). Despite this, the product mixture after precipitation from acetone was used in the next reaction step and a proper purification of the targeted

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• reasons [1]. Halogenated solvents such as chlorobenzene or dichloromethane are widely used in polymer production, but their toxicity and high energy consumption for synthesis make them unwanted for widespread commercial use. Many other dipolar solvents such as dimethyl sulfoxide (DMSO), N,N

• melting point, and difficulties during handling are challenges for a wider application [33] along with some residual toxicity. Alternatively, Vergaelen and co-workers investigated ethyl acetate as a solvent for the CROP of 2-ethyl-2-oxazoline (EtOx) [23]. However, ethyl acetate is not a suitable solvent

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• carbon–carbon iron-catalyzed cross coupling as a key step were developed, capitalizing on the low toxicity and the cheap cost of this abundant metal [10]. For instance, in 1971, Kochi developed an iron-catalyzed alkyl–alkenyl cross-coupling reaction between aliphatic Grignard reagents and vinyl bromides

• NMP as a co-solvent. Indeed, NMP recently proved to be of very high concern due to its acute toxicity, since it was classified as a reprotoxic reagent [16][17]. In order to circumvent this matter and develop new non-toxic and sustainable iron-mediated coupling transformations, efforts were put in the

• , dialkyl phosphates used as leaving groups lead to overall transformations which display a poor atom economy. Moreover, diethyl chlorophosphate (DCP), used as a classic starting material in the dienol phosphates synthesis, is also registered under REACH regulation, and its use brings several toxicity

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• hydrolyzed to the ineffective carboxylate form at basic pH, resulting in decreased clinical efficacy and increased drug-related toxicity. As only the lactone structure of CPT can be transferred through cellular membranes and inhibit topoisomerase I, it is the functional component of CPT lactone form that is

• cells. It is suggested that this difference is due to various reasons, such as decreased drug penetration, development of hypoxic nuclei, and decreased growth [65]. The findings are explained by the differences between conventional cell culture and 3D tumor spheroids. The predicted toxicity/efficacy is

• recent study, cellular cholesterol is directly involved in T cell-mediated cytotoxicity. Cancer cells with cholesterol-rich plasma membranes can evade the immune system by blocking toxicity caused by T cells, but as the amount of cholesterol in the tumor decreases, T cell-mediated cytotoxicity rises [72

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• the perception that radicals cannot be selectively used took place with the introduction of tin hydrides in organic synthesis. Apart from the lower toxicity compared to organomercury reagents, the stability and longevity of tin-centered radicals allowed better propagation of radical chain reactions

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• IC50 0.96 µM) and 4.85 µM (amphotericin B IC50 4.87 µM), respectively. Furthermore, digyalipopeptide A (1) produced IC50 values of 10.07 µM (ampicillin IC50 0.18 µM) and 10.01 µM (ampicillin IC50 1.53 µM) for Staphylococcus aureus and Shigella sonnei, respectively. The selectivity and toxicity profile

• 10.01, 18.71, and 10.01 µM, respectively. The laboratory standard itself produced IC50 of 1.53 µM for Shigella sonnei, Shigella flexneri 1.76 µM, and Staphylococcus aureus 0.18 µM, respectively (Table 3). The selectivity and toxicity profile of compound 1 was also investigated using normal cell lines

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• relatively low cost of these CDs and in particular the low toxicity of γ-CD are advantageous for potential drug delivery. Furthermore, the amorphous nature of highly water-soluble CD derivatives (e.g., hydroxypropyl-CD and sulfobutyl ether CD) precludes their formation of crystalline inclusion complexes

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• of each strategy, as well as the challenges remaining to be tackled. Keywords: enantioselectivity; grayananes; oxidation; 1,2-shift; total synthesis; Introduction The Ericaceae are a large plant family, with over 4250 known species all around the world [1]. While Ericaceae’s toxicity has been known

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• include their synthetic availability, wide opportunities for rational structure design, generally lower toxicity, air and water stability, metal-free nature, and the scalability of their production and use. These features have made organocatalysis a prospering area and an even more promising methodology