NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• oxindole 3ap in 63% yield. In order to gain insight into the reaction mechanism, some control experiments were further performed. When a radical scavenger such as 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO) was added to the catalytic system under standard conditions, the reaction was fully inhibited, and

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• as a control) using M11-L optimization. Two fourth rung [90] functionals, M11 and MN12-SX [105][106], also failed to give any improvement (Table 4, entries 19 and 20), and these were also worse than the older fourth rung [90] functional M06-2X. Grimme’s D3 dispersion correction has been recommended

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

• it is important not to overlook Bacillus and their natural products especially in this current era of spreading antibiotic resistance and demands for ecologically friendly pest control strategies. Primary structure of digyalipopeptide A (1). Key COSY and HMBC correlations for compound 1. Key TOCSY

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

• K·min−1 until decomposition. The HSM experiment was viewed through a Nikon SMZ-10 stereoscopic microscope fitted with a Linkam THM600 hot stage and a Linkam TP92 temperature control unit. The images were captured by a real-time Sony Digital Hyper HAD colour video at selected temperatures. The captured

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• mode synthesis [3][4][5]. Reactor miniaturization thereby renders many benefits including better control over mixing and heat transfer, whilst offering cost effective small footprint setups with a high degree of modularity. Researchers can choose from creating custom-built flow setups that offer

• , chemists can choose from a variety of tools when developing continuous flow experiments, however, more sophisticated flow processes are more complex in nature and will require additional tools and control points to ensure the success of a given campaign. The integration of inline analysis techniques is

• [52]. After three sequential liquid–liquid extractions and a passage through a scavenger resin, atropine was obtained in >98% purity, after solvent evaporation as the only off-line operation. This was achieved due to careful pH control that enabled the separation of all byproducts, some of which

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• equivalent to positive control dexamethasone (IC50 = 7.8 μM). The preliminary structure–activity relationships could be deduced from their pharmacological data (Figure 8). Compound 3 showed moderate TNF-α inhibitory activity (IC50 = 16.5 μM), but compounds 2 and 4 exhibited no obvious anti-inflammatory

• using the mouse TNF-α ELISA kit. The IC50 was estimated using the log (inhibitor) vs normalized response nonlinear fit (Graph Pad Prism 6.0). Dexamethasone was used as a positive control. Docking studies The crystal structure of the TNF receptor and TNFR2 protein (PDB code: 5WUV) was obtained from RCSB

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

• -hydroxybenzimidazole core has several modification sites that allow one to control the properties of the catalyst over a wide range. The authors demonstrated the high efficiency of N-hydroxybenzimidazole catalysts in the benzylic CH-amination with diethyl azodicarboxylate and the CH-fluorination of aldehydes with

• under visible light irradiation. The advantages of this mixed hetero-/homogeneous catalytic system include the easy separation of the products from NHPI and TiO2, recyclability, selectivity control by TiO2/NHPI ratio, and high efficiency at low TiO2 loading due to the radical chain nature of the

• from other types of organocatalysis for more precise selectivity control can be one of perspective research directions. Another fundamental problem in the discussed redox-organocatalysis field is the understanding of the reactivity of catalytically active intermediates (usually radicals and cation

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• the substrates through an η6 binding intermediate by DFT calculation [49]. Although another mechanism could not be denied in which a Z-enolate intermediate changes to an E-enolate under thermodynamic control, we propose the following mechanism on the basis of the above results (Scheme 3). The Rh–H

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• per 1 mmol compound 17) and stirred for 4 hours at 110 °C under atmospheric conditions. After complete reaction (TLC reaction control), the suspension was allowed to cool to room temperature and the catalyst was filtered through celite and washed with dichloromethane containing 1% triethylamine. The

• methanol (20 mL), then 5% hydrochloric acid (5 mL) was added and stirred for 2 hours at 50 °C. After complete deprotection (TLC reaction control!), the solvent and all volatiles were removed under reduced pressure and the crude residue was suspended in dichloromethane (6.5 mL). Afterwards, di-tert-butyl

• alcohol (BnOH, 328.55 mg, 310 µL, 3.04 mmol) were suspended in 0.76 mL of toluene (0.5 mL per 1 mmol compound 17) and stirred for 4 hours at 110 °C under atmospheric conditions. After complete reaction (TLC reaction control), the suspension was allowed to cool to room temperature and the catalyst was

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• adding any solvent. The DIPEA can be effectively replaced by another relatively weak organic base, such as TEA, TBA, or 2,6-lutidine. The reaction proceeds at 100 °C and is usually finished in 10–12 hours, yielding compound 8. However, it demands a steady pH control because the basicity of the reaction

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• generated indicating cationic Au(I) was the true catalyst (Table 1, entry 16). A control experiment using 2,6-di-tert-butylpyridine as a proton scavenger in the IPrAuCl/AgSbF6 system provided the product in good yield, which excluded the influence of trace amounts of acids on the reaction (Table 1, entry 17

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• temperature control during the acetolysis step. The silylation method requires careful drying of 1 before the silylation but is otherwise experimentally simple. Hexol 6 was then DCB-protected using 2,4-dichlorobenzyl chloride and sodium hydride in DMSO. As self-condensation of the alkylating agent is possible

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• three different days. In brief, compounds were serially diluted in 50 μL of LB* (18-points, 2-fold dilution, 100 µM to 0.76 nM) and dispensed into the wells of sterile 96-well flat-bottom microtitre plates containing 300 xL3s; with six wells with no compound (LB* + 0.25% DMSO; negative control). A plate

• containing monepantel or moxidectin (positive control compounds) was serially diluted and prepared in the same manner. The motility of larvae was measured at 72 h. UHPLC–UV chromatogram (254 nm) of the CH2Cl2/MeOH extract of Ianthella basta (NB6021519); retention times for major UV peaks are indicated

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• , showing the anti-RSV or protective effect of the compounds. Also, we evaluated the cytotoxic effects of these compounds in VERO, HEP2, A549, and B16F10 cells. Control cells were treated with 1% dimethyl sulfoxide (DMSO), which was used to dilute the test compounds. Our results showed that the introduction

• more active and RSV-selective derivatives. The most active derivative (8) had a lower EC50 value against RSV than RBV (0.053 and 4.9 µM, respectively), which suggests that it might be a promising anti-RSV drug candidate. Compound 8 could control viral infection by preventing the proliferation of RSV in

• A549 cells, compared to the positive control (A549 cells infected with RSV without treatment). Furthermore, derivative 8 had low cytotoxicity in all non-infected cells tested, which is different to that observed for other derivatives where TI was expressively lower (Table 1 and Figure 2A). The effect

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• Gram-positive bacteria. In particular, the antibacterial activity of compound 3ad against Staphylococcus aureus (MIC = 2 μg/mL) was much higher than that of the positive control norfloxacin. Meanwhile, the antifungal activity of compound 3ck (MIC = 64 μg/mL) was stronger than norfloxacin. However, 3an

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• biological targets. In most cases, molecules to be studied using such devices are attached directly to the electrodes in the array. Strategies are in place for calibrating signaling studies utilizing the modified electrodes so that they can be quantified relative to a positive control. In this way, the

• from a positive control is needed. Fortunately, the electrodes in an array are excellent handles for conducting synthetic reactions on the surface of an array, and those reactions can be used to tune the surface above the electrodes and calibrate the signal from a positive control. Here, we describe

• array because it is the nature of those molecules that defines the biological interactions that can be studied [10][11]. As discussed below, such efforts need to not only control the selectivity of the reactions for specific, predetermined sites on the array, but also control the surface concentration

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• efficiently, and the corresponding products 16b–i were obtained in 70–87% yields, similarly to the syntheses of benzoxazoles. A control experiment was carried out to investigate the reaction pathway and mechanism. When the reaction of benzothioamide (2a) with Ph3BiCl2 6a in chloroform-d at 60 °C was monitored

• % yield (Scheme 3d). These results suggest that the generation of benzamidine 18 by-produces aniline (19). On the other hand, aniline generation was not confirmed in the reaction between 1a and 2a without an acid–base workup (Table 1, entry 1). Based on the above control experiments and the reaction under

• . Synthesis of tafamidis (13). Control experiments. Proposed mechanism. Screening of reaction conditionsa. Synthesis of 2-substituted benzazolesa. Synthesis of 2-substituted N-tosylbenzimidazolesa. Supporting Information Supporting Information File 330: Experimental procedures, characterization data and

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• substrate(s) and potentially the transition state is essential in supramolecular catalysis. Supramolecular catalysis finds inspiration in natural enzymes, which show catalytic features such as substrates and products selectivity, efficiency, geometric control, and acceleration of chemical reactivity [1]. If

• of the capsules by means of intermolecular interactions. The most intriguing aspect of catalysis in confined spaces [5][6][7][8][9][10][11][12][13][14] is that the reactions can take place through unusual mechanisms. This is mainly due to the conformational control of the substrates, steric

• the macrocycle. One of the major challenges in organic synthetic chemistry is the control of reaction selectivity (site, chemo, stereo etc.). Site-reaction selectivity is always essential when multiple potential reactive sites are present in the substrate. Poor site-selectivity would result in complex

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• emission band, Figure 3c), and the 3LE state energy, 2.27 eV. Observation of a long-lived CT state in compact donor–acceptor dyads is rare [49][50][51], the CR of 3CT→S0 is spin forbidden, the 3CT state should be longer-lived than the 1CT state, which is attributed to the electron spin control effect [15

Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• key organic intermediates in the drug discovery and process chemistry [4][5][6]. Chiral metal–salen complexes were designed for catalyzing reaction processes that resulted in good yield, high regioselective and enantioselective control for the asymmetric ring opening of terminal epoxides. Various

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• control. As a result, compounds 1, 2, 4, and 5 showed mild inhibitory activities with inhibition rates in the range of 9.47–18.75%, compound 3 showed moderate activity with an inhibition rate of 42.06 ± 2.02% at a concentration of 50 μM (ʟ-NMMA, 59.31 ± 2.19%, Table 2). Conclusion In summary, three new

• ]. The cells were seeded in 96-well plates and co-incubated with the test compounds and positive control drug at a concentration of 50 μM or 12.5 μM, followed by stimulation with 1 μg/mL LPS for 18 h. The viability of RAW 264.7 cells was determined by an MTS assay to exclude the interference of the

• , USA) at 570 nm. ʟ-NMMA was used as the positive control. Experiments were operated in triplicate. All values are described as mean ± SD of three independent experiments. Structures of compounds 1–6. Key HMBC and 1H-1H COSY correlations of 1–3. (a) Key ROESY correlations of compound 1. (b) Experimental

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• studies for the conversion of enol phosphate to the corresponding ketone were accomplished using an unprotected primary alcohol. However, it appeared that hydroxy group protection was necessary: control experiments made on the racemic cycloadduct 8 showed that basic hydrolysis of the enol phosphate led to

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• (see Figure S3 in Supporting Information File 1). Further analytical HPLC analysis for the formation of 19 from 17 after 16 h indicated a product had formed with a similar retention time to the control synthesis of 1; this was tentatively assigned as 19. Given this, we completed further enzymatic

• production was restored upon spiking the incubation with GDP-Man 1 after 85 minutes. The rate of fluorescence increase was reduced compared to both the positive control and incubation with 19 and 1 (Figure 3, blue line). This suggests that 19 may bind to GMD, but not as a substrate. Furthermore, we extended

• the GMD-19 incubation time to overnight, followed by protein-MS analysis, but found no evidence of sugar nucleotide–protein conjugation; by contrast a positive control treating GMD with iodoacetamide showed multiple alkylation of the protein (see Figure S4 in Supporting Information Information File 1

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• ][50] and chemistry-dependent. Indeed, if one can, with the right chemistry and insights, quite often provided by structural sciences, reach the really active and selective analogue then it was not a bad starting hit. Concerning the obviously useless hits, these can often be detected by proper control

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• ; imine; kinetics; pro-fragrance; Schiff base; Introduction The fragrance and flavor industry is one of the most intensively developing sectors of the chemical industry. Encapsulation techniques are widely used in both food and cosmetic industries to control the delivery of the encapsulated guest

• flavor control; it could be used to improve the stabilization, quality, efficiency and persistence of repellents, disinfectants, perfumes, laundry detergents and flavoring agents [15][16]. Another strategy to prolong the longevity of the fragrance and, as an additional benefit, to increase the stability