Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• = Ph). Finally, an interesting group of β-ketothioesters 5–8, which are rarely utilized in asymmetric catalysis [45], were employed as nucleophiles in reactions with acceptor E1 (Scheme 7). While additions of various β-ketothioesters, including 5–8, to nitrostyrenes proceeded efficiently, leading to

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• each system was affected differently by the individual components [15]. This shows that the different CFPS systems have different requirements for their composition, which must be highly balanced. At most, pH and ionic strength are general variables that are considered [13]. Since the main influences

• reaction solution in 98 µL 0.5 M HEPES buffer (pH 8.0) in 384-well microplates with a FLUOstar® Omega multi-mode microplate reader (BMG LABTECH, Ortenberg, Germany). The endpoint measurement was set to a gain of 1390, λex 485 nm and λem 520 nm. For the experiments with organic solvents, the corresponding

Selective hydrolysis of α-oxo ketene N,S-acetals in water: switchable aqueous synthesis of β-keto thioesters and β-keto amides

• Haifeng Yu,
• Wanting Zhang,
• Xuejing Cui,
• Zida Liu,
• Xifu Zhang and
• Xiaobo Zhao

Beilstein J. Org. Chem. 2024, 20, 2225–2233, doi:10.3762/bjoc.20.190

• thioesters 2 (2a as an example) A mixture of (E)-3-(ethylthio)-1-phenyl-3-(phenylamino)prop-2-en-1-one (1a, 70.8 mg, 0.25 mmol) and DBSA (87.9 mg, 0.25 mmol) in water (2 mL) was stirred at reflux in an oil bath under air for 5 h until 1a was completely consumed, as confirmed by TLC monitoring. Then, the pH

• water (2 mL) was stirred at reflux in an oil bath under air for 24 h until 1a was completely consumed, as confirmed by TLC monitoring. Then, the pH value of the reaction mixture was adjusted to neutral using a 10% CH3COOH solution, and the reaction mixture was extracted with CH2Cl2 (3 × 20 mL). The

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• signals clearly corresponds to the heterocycles depicted above. Figure S8 (see Supporting Information File 1) shows 1H NMR spectra for Ph-substituted O,S,Se-DHPMs 2a,h,o. It can be seen from them that when going from oxygen to selenium (2h→2a→2o), the signals of both NH groups shift to down field (7.87

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

Cage-like microstructures via sequential Ugi reactions in aqueous emulsions

• Rita S. Alqubelat,
• Yaroslava A. Menzorova and
• Maxim A. Mironov

Beilstein J. Org. Chem. 2024, 20, 2078–2083, doi:10.3762/bjoc.20.179

• structures existed only within a narrow pH range: when the pH value dropped below 5.5, the chitosan easily dissolved, and when the pH value was above 7, the CMC domains swelled and lost their properties. It is known that the Ugi reaction can be successfully used to obtain cross-linked gels based on

• polysaccharides [18]. Therefore, to stabilize such structures, the Ugi reaction in water was chosen, for which this particular pH value range is optimal [19]. The amino groups of chitosan and the carboxy groups of CMC reacted with each other and formed a stable structure that was no longer sensitive to changes in

• pH value. According to atomic force microscopy (AFM) data, the resulting particles had a domain structure and were similar in appearance to raspberries [20]. An interesting feature of the resulting particles was the high efficiency as Pickering emulsifiers: even at a concentration below 0.3 g/L

Understanding X-ray-induced isomerisation in photoswitchable surfactant assemblies

• Beatrice E. Jones,
• Camille Blayo,
• Jake L. Greenfield,
• Matthew J. Fuchter,
• Nathan Cowieson and
• Rachel C. Evans

Beilstein J. Org. Chem. 2024, 20, 2005–2015, doi:10.3762/bjoc.20.176

• contrast, for AAPTAB, the process was much slower, with minimal change over 1 hour, but near-complete transition to the E isomer after 20 hours (Figure 4b). The excess acid added in these experiments generates a pH value of 0.4 in the samples. In comparison, the calculated pH change expected due to the X

• -ray radiolysis of water (see section 6, Supporting Information File 1) was found to be from pH 7 to ≈ pH 5–6 for the X-ray irradiation doses used in these experiments. Interestingly, both AzoTAB and AAPTAB show little difference in their time-dependent absorbance spectra from the Z-rich PSS over the

• course of 200 minutes at pH 5, 6 and 7 (Figures S8 and S9, Supporting Information File 1). This suggests that the X-ray-induced formation of H+ ions alone may not be strong enough to induce Z–E isomerisation on the millisecond timescales on which structural changes were observed using SAXS. We note that

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• zwitterionic water-soluble hypervalent iodine reagent (phenyliodonio)sulfamate (PISA). In water, PISA is strongly acidic, and the pH value can reach 2.05 in a saturated aqueous solution. With PISA, various indoles have been synthesized via C–H amination of 2-alkenylanilines involving an aryl migration

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

• compatibility of the GBB reaction with typical KTGS conditions, such as aqueous solvent at near-physiological pH and high dilution, and the achievement of selective ligand amplification. First, molecular modeling studies were carried out to verify that building blocks and intermediates could bind the target

• -reacted with the aldehydes to yield 5-iminoimidazoles 56. When benzamidine (54, R2 = Ph) was used, aldehydes bearing electron-rich groups gave the products in higher yields compared to those with electron-poor groups. This study demonstrated that the GBB reaction could take place when acyclic amidines

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• , value for Ar = Ph] [14][15][16][17][18] (Figure 1B). 5-Aryldeazaalloxazines 2 have been found to be even more powerful reductants than 1 due to their more negative ground-state reduction potential by ca. 300 mV. Moreover, 2 exhibits higher photostability than 1. Consequently, 5-aryldeazaalloxazine 2f

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

• 0.8. Cultures were incubated for 14 h, at 200 rpm, at 18 °C. Subsequently, cells were centrifuged at 10,000 rpm for 30 min at 4 °C. The resulting cell pellets were resuspended in 20 mL of LanA starting buffer (20 mM Tris pH 7.5, 500 mM KCl, 10% glycerol) and lysed by sonication (4.0 seconds on, 10

• purifications using affinity chromatography with a 1 mL His Trap nickel affinity column. Sonication lysis was performed and centrifuged during 30 min, at 8,000 rpm, 4 °C. The supernatants were loaded into the column. The column was washed with 5 column volumes of LanA wash buffer 1 (20 mM Tris pH 7.5, 500 mM

• KCl, 10% glycerol, 0.5 mM imidazole), followed by 10 column volumes of LanA wash buffer 2 (20 mM Tris pH 7.5, 500 mM KCl, 10% glycerol, 30 mM imidazole). Finally, the elution was performed with 3 column volumes of LanA elution buffer (20 mM Tris pH 7.5, 500 mM KCl, 10% glycerol, 750 mM imidazole

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• moiety under the influence of water. The appearance of HCl in these cases was identified by the specific odor and detected by pH measurements. It is likely that this catalytic amount of HCl is enough for the conversion and formation of the amides 10. To confirm the influence of HCl and its necessity to

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• . Heating 5 with hexylamine or aniline in refluxing acetic acid successfully led to the formation of the targeted aromatic diimides bearing either N-hexyl (7-Hex) or N-phenyl (7-Ph) substitutions in good yields. The same strategy was employed to create the imide-capped anthracenes 8-Hex and 8-Ph

• evaporation of CH2Cl2/MeOH solutions and characterized by X-ray crystallography. 7-Ph crystallizes in the Pbcn space group into a solvent superstructure of π-stacked columns of 7-Ph. The imide groups are pointed in alternating directions within a stack. While this may occur in part as a consequence of the

• steric demands of the N-phenyl groups, there are also C–H···π interactions between phenyl groups of adjacent π stacks, with the closest Ph centroid to H distance being 2.613 Å (Figure 2a). Additionally, the middle carbonyl oxygens are in short contact (2.376 Å) with the 7- and 8-H atoms of the

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

• for methyl malonyl-CoA and malonyl-CoA in the enzymatic conversions. After careful and systematic optimization of the reaction conditions, such as the stoichiometry of the PKS modules and pH, along with the application of a NADPH recycling system, JuvEIV/JuvEV-catalyzed enzymatic conversions of 77–79

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• enzyme RagaA7 was produced in a Bacillus subtilis host and characterized to be a neoagarotetraose-producing GH-16 family endo-type β-agarase with a pH and temperature optima being 7.0 and 50 °C, respectively. Another thermostable neoagarotetraose-producing GH-16 endo-type β-agarase rAgaA was identified

• and cloned from deep-sea-derived Microbulbifer sp. JAMB-A94 with pH and temperature optima being 7.0 and 55 °C, respectively [26]. The recombinant enzyme was likewise produced using a B. subtilis host. The crystal structure of the catalytic domain was determined to show a β-jelly roll fold with

• bridges, relatively short length of the surface loops, and the increased number of Pro and Arg residues [29]. A truncated β-agarase gene without the carbohydrate-binding modules (Aga16A-ΔCBM) from the marine Microbulbifer sp. BH-1 was cloned and expressed in Escherichia coli with pH and temperature being

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

• -responsiveness, and molecular functional tunability of synthetic supramolecular systems can be precisely controlled through the delicate design and synthesis of organic molecules [9][10][11][12][13][14]. Synthetic supramolecular systems can respond to various external stimuli, e.g., light, pH, organic solvents

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• an equilibrium of Cl–I(Ph)–OTFA–AlCl3 and [Cl–I(Ph)][OTFA–AlCl3], rather than PhICl2 being the active species. On the other hand, bromination using PIDA and AlBr3 was more efficient, wherein the intermediate Br–I(Ph)–OAc–AlBr3 was formed as active brominating species. Similarly, PhIBr2 was higher in

• bromide is coordinated by an acetate ligand to produce the active brominating species Br–I(Ph)–OAc–AlBr3 (I-3–Br). Then, 2-naphthol adds to the iodine(III) species to release the activated Br3Al–OAc ligand through transition state TS2–Br (ΔG‡ = 11.7 kcal/mol), which leads to the protonated intermediate I

• -4–Br. The next step is a deprotonation assisted by the released Br3Al–OAc species. This allows the formation of the AcO–AlBr2 salt via TS3–Br and the trans intermediate I-5–Br, which contains a Br–I(Ph)–O–naphthyl bond of 2.14 Å length. The last step is the bromination of I-5–Br by isomerization to

Mining raw plant transcriptomic data for new cyclopeptide alkaloids

• Draco Kriger,
• Michael A. Pasquale,
• Brigitte G. Ampolini and
• Jonathan R. Chekan

Beilstein J. Org. Chem. 2024, 20, 1548–1559, doi:10.3762/bjoc.20.138

• . After the extractions were finished and dried by rotary evaporation, the extract was resuspended in basic water (pH 10 using NaOH) and vacuum filtered to remove insoluble particulates. Liquid–liquid extraction was performed three times with basic water and DCM. The DCM layer was collected and dried

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

• ITC200 isothermal titration calorimeter (Microcal-Malvern Panalytical, Grenoble, France). The lyophilized LecA protein was dissolved in a buffer composed of 20 mM Tris.HCl (pH 7.5), 100 mM NaCl and 100 μM CaCl2 with 5% or 10% DMSO final. All compounds were first dissolved in DMSO then in same buffer for

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

• to various aryl moieties except for those containing strong electron-withdrawing substituent (i.e., -CN, -NO2). 3-Cyclohexenones 2 bearing a halogen group (i.e., -Cl, -Br) as well as an electron-donating group (i.e., -Me, -OMe, -Ph) worked well under the optimized reaction conditions, delivering the

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• Discussion This study evolved from a parallel exploration of reactions involving unsymmetrical phenyl(mesityl)halonium salts, i.e., Ph(Mes)X+. DFT analysis revealed similar structural trends to our previous work [21] when we expanded the halogens to include astatine (At). Due to its radioactivity and short

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

• . Acknowledgements We thank Dr. Yong W. Kim (University of Toledo) for NMR assistance. Mr. Babatunde Obadawo (University of Toledo) is acknowledged for collecting the high-resolution mass spectrometry data. We acknowledge Dr. Navdeep Kaur’s Ph. D. for her contributions in her Ph. D. thesis titled “Selective

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• a substituent R5 located at carbon C-4 gave good yields, except for methoxy and benzyloxy which did not work at all. Dienes derived from 1,3-diketones (R6 = Me, Ph) gave similar yields to those obtained from dienes derived form β-ketoesters, although yields were slightly lower in case of R6 = Me

• intramolecular nucleophilic attack of the oxygen to the halide to give intermediate U and subsequent ring-cleavage. The reaction of 3-ketoamide 34a (R3 = Me, R4 = Ph) with 3-chloro-, 3-bromo-, and 3-iodochromone showed that the yields strongly depend on the type of halogen atom located at position 3 of the

• chromones, presumably due to the electron-donating character of the methoxy group and the lower electrophilicity of the chromone. But this trend was also not general. Similar yields were obtained for ketones (R3 = Me, Ph) or esters (R3 = OMe). Treatment of 2-(salicyloyl)furan 35a with iodine in the presence

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

• -morpholino)propanesulfonic acid (MOPS) buffer (pH 7.5), and the cells were disrupted by ultrasonication to obtain the cell extract. Cell debris was removed by centrifugation (14,000g, 15 min). The proteins were purified by Ni-NTA agarose chromatography, desalted, and concentrated by centrifugation (8,000g

• ]. In vitro enzymatic assay All reactions were performed in 50 mM Tris-HCl buffer at pH 8.0. For conversion of 9 by AlpG or JadH, the reaction mixtures (50 μL) consisting of 10 μM FAD, 125 μM NADPH, 100 μM 9, and 25 μM AlpG or JadH were incubated at 30 °C for 5 min and analyzed by HPLC directly. For

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

• -neutral phosphinamide and a negatively charged phosphinic acid derivative had excellent stability in water at pH 7.4, but only the charge-neutral compound inhibited human CDA, similar to previously described 2'-deoxyzebularine (Ki = 8.0 ± 1.9 and 10.7 ± 0.5 µM, respectively). However, under basic

• in H2O. Removal of toluoyl groups was accomplished in aq NH3, providing pure α- and β-nucleoside of Va and Vc, respectively, carrying a negatively charged phosphinic acid group. These compounds were found to be stable in sodium phosphate buffer at pH 7.0 as no decomposition was observed in NMR

• equation, such as Lineweaver–Burk, Hanes–Woolf and Eadie–Hofstee transformations [71]. Then, KM for the substrate and Ki for each inhibitor were calculated, assuming competitive nature of the inhibitors (Table 1). Initially, we performed this assay in 50 mM sodium phosphate buffer at pH 7.4 (25 °C) and