Development of a flow photochemical process for a π-Lewis acidic metal-catalyzed cyclization/radical addition sequence: in situ-generated 2-benzopyrylium as photoredox catalyst and reactive intermediate

• Masahiro Terada,
• Zen Iwasaki,
• Ryohei Yazaki,
• Shigenobu Umemiya and
• Jun Kikuchi

Beilstein J. Org. Chem. 2024, 20, 1973–1980, doi:10.3762/bjoc.20.173

• ). Moreover, the yield of 3a was improved when the concentration of 1a was lowered from 0.1 M to 0.05 M (Table 1, entry 8: 61%). Meanwhile, further reducing the catalyst loading from 5 mol % to 2 mol % resulted in a significant decrease in yield (Table 1, entry 9: 28%). When the reaction was scaled up from

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• . The use of chlorobenzene slightly improved the yield to 66%. The reaction in dioxane at 90 °C, entry 6, had a 96% yield. This was a surprising outcome as Keeting observed no reaction in dioxane at rt, suggesting the concentration of Cs2CO3 is significantly increased at this temperature. With the

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• )acetate at the bottom of the vial after a few hours of storage in the fridge. The solid can be easily re-dissolved by gentle heating, and without affecting the product concentration and integrity. After a brief screening, Pd(dba)2 and X-Phos (in a 1:2 ratio) were selected as the catalyst system for the

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

• . 1.3 Compartmented and enzyme-mediated reactions Compartmentation of reaction media has already found many applications in chemistry. Amphiphilic molecules can associate in water to nanometer-sized micelles, above a certain critical concentration. Such micelles are characterized by a lipophilic core

• interactions with the target were synthetized. After optimization of the reaction medium and of the concentration of reactants, and after setting up an analytical method relying on UPLC with tandem quadrupole detector, the on-target KTGS experiments were conducted. In a first set of experiments, a single

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

• various levels to ensure the production of high-quality peptides [19]. As an example, subtilin production is autoregulated based on the extracellular concentration of the molecule. At the same time, subtilin expression is also controlled by the spaRK operon and the sigmaH (σH) global regulator, which

• cellulosin samples displayed robust bacteriostatic activity at the highest estimated concentration of 5.6 µg/mL and 4.8 µg/mL, respectively, compared to the bacteria grown in LB media (control), and lower but statistically significant effects at lower concentrations (Figure 5). The immature peptides CloA1

• precursor peptide and CloA2 precursor peptide showed no discernible effect at the same concentration. These findings highlight a change in the activity after the leader peptide's proteolysis and the presence of mature lanthipeptides (Figure 5). For clostrisin, as it has no post-translational modifications

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• reactant concentration [46]. The reaction mixture was kept in a flask under stirring and pumped through the Flux cell and back to the flask. The flow rate was increased to 300 μL/min to faster flush out the evolved hydrogen gas from the cell. The Flux cell was operated in the galvanostatic mode at 9 mA

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• conclusion holds for any photoswitch where only one isomer can be isolated successfully. During the measurement and at the PSS, the relative concentrations of the two isomers are unknown. The total absorbance (Absobs) at a given total concentration (c) of the sample is a linear combination of the absorbance

• scaled subtraction [14]. Another powerful method to obtain the spectrum of the second isomer is global and target analysis, where time-resolved spectra can be analyzed to find the number of spectral components and the evolution of their concentration over time [36][37]. Additional information, such as a

• kinetic model describing the components and the non-negativity constraint on the absorbance, can help to guide the decomposition of the data into chemically meaningful concentration traces and species-associated spectra (SAS) [38]. Global and target analysis is one of the methods employed in recent

Oxidation of benzylic alcohols to carbonyls using N-heterocyclic stabilized λ³-iodanes

• Thomas J. Kuczmera,
• Pim Puylaert and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 1677–1683, doi:10.3762/bjoc.20.149

• proposed in the initial experiments is not a Lewis acid activator but just a chloride source. Further optimization studies improved the yield to 78% of 4b using a concentration of 0.20 M of the alcohol and 1.4 equiv of 1a (see Supporting Information File 1). Finally, all NHIs were tested under the

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

• -terminally methylated nisin retains its antibiotic activity, with MIC (minimal inhibitory concentration) values of 1 µM and 4 µM against Lactococcus lactis and Bacillus subtilis, respectively. Haloduracin is a two-component lanthibiotic that is methylated at both cyclised N-termini by CypM. These experiments

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

• , was further diluted to prepare various aliquots with a concentration ranging from 1.0 × 10–4–0.1 mM in order to estimate the critical aggregation concentration (CAC) by using static light scattering (SLS). An aqueous solution of DA11 was estimated to have a CAC of <6.0 μM (Figure S5, Supporting

• normalized by the concentration of the solution to yield the molar scattering intensity. Ten replications were performed, and the data was averaged to show the molar scattering intensity and the error standard deviation. WAXD WAXD of DA scaffolds was measured on a sapphire substrate (φ = 2.0 cm) using a

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• attributed this to the increased solubility and concentration of NFSI in the AIBN conditions, which were performed at elevated temperatures, promoting facile trapping of a primary radical. In contrast, the decatungstate conditions, which operated at room temperature where NFSI is not completely dissolved and

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• (Table 1, entry 11). Subsequently, the effect of concentration on the reaction outcome was also studied. In dilute conditions, both the yield and enantioselectivity of the product 3aa were improved to 80% and 94%, respectively, at room temperature (Table 1, entry 12). Taking into account the results of

Towards an asymmetric β-selective addition of azlactones to allenoates

• Behzad Nasiri,
• Ghaffar Pasdar,
• Paul Zebrowski,
• Katharina Röser,
• David Naderer and
• Mario Waser

Beilstein J. Org. Chem. 2024, 20, 1504–1509, doi:10.3762/bjoc.20.134

• L1000 at 589 nm ([α]D values are listed in deg/(dm(g/cm3)); concentration c is given in g/100 mL). Unless otherwise stated, all chemicals were purchased from commercial suppliers and used without further purification. Dry solvents were obtained from an MBraun-SPS-800 solvent purification system. All

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• a final concentration of 5% or 10% DMSO. The 200 μL sample cell containing LecA (concentrations ranging from 200 to 300 μM) was subjected to injections of ligand solution: 20 injections of 2 μL (2–3 mM, depending on the ligand) at intervals of 120 s while stirring at 850 rpm. Control experiments

• total heat released as a function of total ligand concentration for the titration shown in the upper panel. The solid line represents the best least-square fit to experimental data using a one site model. (A) Enthalpy–entropy compensation plot of compounds 1–5 from ITC analysis. The dotted green line

Synthesis of 2-benzyl N-substituted anilines via imine condensation–isoaromatization of (E)-2-arylidene-3-cyclohexenones and primary amines

• Lu Li,
• Na Li,
• Xiao-Tian Mo,
• Ming-Wei Yuan,
• Lin Jiang and
• Ming-Long Yuan

Beilstein J. Org. Chem. 2024, 20, 1468–1475, doi:10.3762/bjoc.20.130

• reaction media led to higher yields. More precisely, dimethoxyethane (DME) gave a superior result to THF, affording 4aa in 82% yield (Table 1, entries 10–16). Subsequently, modification of the reaction temperature or concentration turned out to be unsatisfactory (Table 1, entries 17–19). We also added 4 Å

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• , in this case, the formation of carbinolamine 6a becomes predominant (45%), despite a small quantity of N,O-aminal 5j (14%) is also produced, by virtue of the alcohol released from the starting acetal 4j. Probably, the higher water concentration in acetonitrile shifts the equilibrium in favour of 6a

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• the reaction efficiency, we screened several additional parameters including solvents and concentration. In these cases, we found that while both acetonitrile and MeNO2 (0.25 M) were suitable solvents, other solvents in general afforded no product formation (Table 1, entries 2–6). Lower catalyst

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• in the appropriate vicinity for the reaction to take place in appreciably good yields (84%). The barium cation template is the key for the reaction, as is the base concentration for effective hydride transfer (Scheme 14) [29]. They also extended the scope of the intramolecular Cannizzaro reaction to

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• overall small extinction coefficient of the radical anion (Figure S6 in Supporting Information File 1 and the corresponding discussion). To investigate the triplet reactivity of Aza-H, a lower concentration of 4CP (5 mM) was used, quenching the singlet excited photocatalyst only partially (η ≈ 25%) and

• solution of Aza-H with a lower concentration of TsNa (200 µM). We presumed this would enable us to exclusively monitor Aza-H•+ quenching by TsNa, since any triplet Aza-H would be deactivated by oxygen (see above). The ionization efficiency of Aza-H exhibits a quadratic dependence on the laser intensity

• . Consequently, focussing the laser on a narrow excitation spot on the sample ensured a significant generation of Aza-H•+ while minimizing the concentration of triplet-excited Aza-H. Initially, the same amount of radical cation is detected after the addition of TsNa, but the Aza-H•+ signal at 460 nm decays much

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• the amount of solvent was doubled. We used a higher concentration of reactants in our studies as the yield of soluble products obtained at lower concentration of reactants was not satisfactory. However, under both conditions, a blackish purple polymeric solid was isolated as major product, labelled

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• . The half-maximal growth inhibitory concentration (GI50) values after 48 hours of exposure were calculated for each compound (Table S1, Supporting Information File 1). The standard anticancer drug cisplatin (CDDP) was used as positive control. The results are viewed as GI50 range plot (Figure 3). The

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• , 30 min) in 10 kDa ultrafiltration tubes (Centriplus YM series, Merck Millipore). Protein concentration was quantified by the Bradford method. AlpJ, JadG, JadH, and E. coli flavin reductase (Fre) were overproduced and purified by Ni-NTA agarose chromatography as described previously [10][11][43][44

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• inhibitory concentration (IC50) of 10 ng/mL, lepistatin A (3), along with two other new chlorinated analogs, that were isolated from Basidiomycete Lepista sordida culture, pauciflorol F (4), isolated from Vatica pauciflora, which is an important building block for the biosynthesis of bioactive polyphenols

• achieved. Under both conditions, virtually no product mixtures were observed. Preliminary biological evaluation To investigate the cytotoxic activity of the indanone derivatives, in total 20 compounds were tested at a concentration of 5 and 50 μg/mL for 72 h in a panel of four histologically unrelated

• ) being active at 5 μg/mL, using a 75% cutoff inhibition at each concentration. On the other hand, MCF-7 and SK-MEL-28 cells were the most resistant ones, with no compound being active at the lower concentration (Figure 5). This evidence of selective cytotoxicity for a specific histological tumor subtype

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• investigated using four different well-defined phosphine substituents-containing Mn complexes with acetophenone and benzyl alcohol as model substrates. Among these, complex Mn1 showed better results with 2 mol % loading and at low base concentration (Cs2CO3; 5 mol %) in tert-amyl alcohol at 140 °C for 22 h

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• (A3BCTD), originally called A3BCTD-QM-∆L3-AL1swap [54], in which loop 3 is deleted and loop 1 is replaced with the corresponding loop 1 from A3A. The residual activity of the A3A mimic on the unmodified oligonucleotide 5'-TTTTCAT as a substrate in the presence of a known concentration of inhibitor was

• measured using the NMR-based assay (Figure 2). The results revealed that both anomers of Va do not inhibit engineered A3A mimic even at elevated concentration in comparison to a control ODN containing FdZ (IId) at pH 6.0. It is very likely that a negative charge in nucleobase Va prevents binding to the

• resulting DNA hairpin. The β-anomer of Va was introduced instead of the target dC in the DNA hairpin with TTC loop and tested in the 1H NMR-based assay monitoring A3A-catalysed deamination of dC hairpin (T(GC)2TTC(GC)2T, wherein C is deaminated) at a 150 mM salt concentration at pH 7.4. Recently, FdZ (IId