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

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• CCl4 to prevent undesired solvent degradation. Furthermore, the direct use of Br2, even if used in low concentration, exhibits limited selectivity towards benzylic bromination, primarily due to co-bromination occurring on the aromatic ring. This side process produces awkward halogenated byproducts that

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• illustrated in Figures S37–S41 (Supporting Information File 1). This serves as good evidence that the synthesized compounds exhibit no signs of aggregation in DMSO within the assessed concentration range (i.e., 2.5–45 μM). Electronic structure calculations Gas-phase computational investigations were conducted

• 40 μM solutions of the DCPQs and DPQDs on a Cary 100 Bio spectrophotometer using 1 cm quartz cells. All solvents were HPLC grade (purchased from Fisher) and stored over 4 Å molecular sieves. The absorption intensity at λmax was then plotted against the concentration in all cases to confirm, by

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• most successful modification. The potential of the truncated derivatives was further illustrated by the thiazolopyridone and thiadiazolopyridone compounds 4a,b, which showed inhibition with IC50 = 88.1 μM and 128.7 μM, respectively. Even though the measured inhibitory concentration was higher than that

• antivirals. Structure of HeE1-2Tyr (1) and of the derivatives synthesized in this work. Analysis of inhibitory activity against SARS-CoV-2 RdRp using primer extension assay. A) Gel-based polymerase assay with a constant concentration of fluorescently labeled template/primer RNA (0.5 µM) and the polymerase

• ) Graphical representation of the inhibitory activity of selected compounds evaluated from the gels obtained in the primer extension assay. The percentage of inhibition (against control) was plotted against the logarithm of the concentration of compounds. The results were fitted to sigmoidal dose–response

Auxiliary strategy for the general and practical synthesis of diaryliodonium(III) salts with diverse organocarboxylate counterions

• Naoki Miyamoto,
• Daichi Koseki,
• Kohei Sumida,
• Elghareeb E. Elboray,
• Naoko Takenaga,
• Ravi Kumar and
• Toshifumi Dohi

Beilstein J. Org. Chem. 2024, 20, 1020–1028, doi:10.3762/bjoc.20.90

• % yield. It is worth noting that the products yielded by these protocols were easily separated as white amorphous solids by concentration and trituration of the obtained residue with diethyl ether. The color of the products indicates that the reactions proceeded without any signs of decomposition

Spin and charge interactions between nanographene host and ferrocene

• Akira Suzuki,
• Yuya Miyake,
• Ryoga Shibata and
• Kazuyuki Takai

Beilstein J. Org. Chem. 2024, 20, 1011–1019, doi:10.3762/bjoc.20.89

• Fe2p peaks and the increase in shake-up peak intensity of the C1s in the XPS spectrum proved the emergence of charge-transfer host–guest interaction in FeCp2-ACFs-150, supported by the red-shift of the G-band in the Raman spectrum. The six-times enhancement in the spin concentration in FeCp2-ACFs-150

• compared with ACFs indicates the spin magnetism of the non-magnetic guest FeCp2+ molecule induced by a charge-transfer host–guest interaction in the nanographene host. The larger ESR linewidth than that expected from the dipolar interaction estimated by the localized spin concentration suggests the

• constant. The spin concentration Nspin for each sample was calculated from the Curie constant. ESR measurements were performed using a conventional ESR X-band spectrometer (JEOL, JES-FA300) at room temperature, where ca 1 mg of samples vacuum-sealed in glass tubes were used. In order to prevent the skin

A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• 14 (69 µM and 18 mM, respectively), suggesting that the probe will be highly useful for detecting lower concentration furans. The maleimide probe was then tested for its ability to detect the naturally produced MMF compounds (Figure 5). Two strains of Streptomyces coelicolor were tested: S

• times) to observe the molecules in their native producers. While this is not ideal, it is still significantly better than the concentration needed without probe (≈260,000 times). Conclusion MMFs are important signaling hormones that induce the production of methylenomycin A. Bioinformatics data suggests

• figure were run at 25-times the extracted concentration. Representative data from three experiments is shown. Conversion of various synthetic substrates when reacted with the maleimide probe.a Conversion of various natural product substrates when reacted with the maleimide probe.a Supporting Information

Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• the efficiency of the reaction, whereas a 19F NMR yield of only 11% was achieved in DMF (Table 1, entries 10–12). Increasing the reaction concentration to 0.2 M in DCM led to a reduction in the 19F NMR yield of 2a to 74% (Table 1, entry 13). Finally, optimisation of the reaction time revealed the

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• , entry 1). Decreasing or increasing the concentration did not improve the yield of 4aa (Table 1, entries 2 and 3). The reaction became rather sluggish in different solvents such as HFIP and Et2O (Table 1, entries 4 and 5). By reducing the equivalents of 2a to 3 equiv and 2 equiv, the yield of 4aa dropped

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• 50% inhibition concentration of selected CYP450 enzymes (IC50). Cis-2,6-disubstituted [2]-ladderanes Brown and co-workers recently proposed cis-2,6-disubstituted bicyclo[2.2.0]hexanes ([2]-ladderanes) as isosteric replacements for meta-benzenes. An exit vector analysis indicated that the substituent

• potential explanation for these observations is an increase in heterocycle basicity on bioisosteric switch of a neighbouring aromatic group. However, the drug-specific half-maximal rescue concentration (RC50 CFTR, lower indicates higher biological activity), indicative of the biological activity, increased

• both 189 and iso-189 in form of the inhibition of prostaglandin PGE2 synthesis by cyclooxygenase-2 (COX-2). Their investigation showed that while 1,3-cuneane 189 requires a 100-fold increase in concentration to reach inhibitory rates comparable to ketoprofen, its isomer iso-189 is inactive against COX

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• allows for release and subsequent detection of heme-ligated iron [47]. Protein concentration was determined using bicinchoninic acid protein quantification assay (Pierce). The oligomeric state was determined by processing the protein through Superdex 200 Increase 10/300 GL analytical size exclusion

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• indicated that CavA specifically oxidizes albicanol (5) and drim-8-ene-11-ol (6) to synthesize 7–9, while other substrates showed no reactivity with CavA (Figure 4c). Following this, we increased the substrate concentration to enrich and isolate these products, elucidating their structures through NMR

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• to the higher concentration of liquid HCl compared to gaseous HCl. A systematic study of hydrochlorination reactions with concentrated solutions of HCl gas in DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone) was recently disclosed by Hammond and Xu (Scheme 7) [51]. These solutions were prepared

• by bubbling HCl gas, generated from NaCl and H2SO4, into dry DMPU. This yields a 14 M solution of HCl in DMPU, a concentration significantly higher than HCl solutions in other organic solvents. Further enhancement of the reaction was achieved through the addition of acetic acid. The reaction displays

• affording chloride 51 as a mixture of cis- and trans-isomers. The hydrochlorination of 1,2-dimethylcyclohexene (29) resulted in high selectivity for trans-30. The authors also showed that an increase in ethanol to 40 equivalents led to a dramatic drop in yield, likely due to an overall lower concentration

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• aggregations in aqueous solution, as observed by dynamic light scattering (DLS), cryoTEM, and concentration-dependent surface tension measurements [40]. Despite the small size (≈10 nm in hydrodynamic diameter), the aggregation of these fullerene moieties was not ideal for biological applications as

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• . At a concentration of 182 μM, murecholamide exhibits biological activity in inhibiting the migration of HT29 cancer cells. The second HSM is noaoxazole (39), which was discovered in Streptomyces sp. HR41 [79]. This substance has a chemical structure with a methylated oxazole ring at the end of a

• ]. Nocarjamide exhibited biological activity by activating Wnt signaling at an effective concentration of 20–40 μM. Wnt signaling plays an important role in a number of vital processes, such as the formation of various tissues and the differentiation/proliferation of eukaryotic cells [122]. It is interesting

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• (ROSs) [28]. Crocins can inhibit the activity of acetylcholinesterase and increase the acetylcholine concentration, thus improving the learning and memory ability of the brain [29]. Moreover, crocins prevent the abnormal aggregation of amyloid β-protein (Aβ), microtubule-associated protein tau, and α

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• source such as green LEDs or a compact fluorescent lamp (CFL) were used only a small decrease in yield could be observed, although 4 hours of irradiation were needed to reach full conversion using CFL (Table 5, entries 8 and 9). The concentration, a factor expected to play an important role in a three

• -component reaction, had surprisingly little influence on the transformation. At lower concentration only a slight decrease of yield was observed, whereas higher concentration led to a similar yield (Table 5, entries 10 and 11). The source of nucleophilic alkyne was evaluated, changing the counter ion from

• -tuning of the reaction conditions was performed. Increasing the concentration to 0.1 M afforded a comparable yield (Table 8, entries 1 and 2). Similarly, the equivalents of alkynyl-BF3K 5a could be reduced to 1.5, a further decrease started to impact the yield (Table 8, entries 3 and 4). Carrying out the

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• five compounds (1–5, Figure 1). The production of these siderophores was high under iron-starvation conditions with 0.1 µM FeCl3 in the media, and began to decrease when the concentration of Fe3+ ions reached 0.5 µM (Figure S1, Supporting Information File 1). The HRESIMS data of the major compound 1

• were collected and spread onto 2xR2A agar plates with chloramphenicol (30 µg/mL) and kanamycin (50 µg/mL). The plates were incubated at 30 °C until colonies formed. The disruption of varG was confirmed by PCR amplification. Effect of ferric ion (Fe3+) concentration on production of variochelins An

• overnight culture of Variovorax sp. H002 in 2xR2A liquid media was transferred to small baffled acrylic flasks containing 15 mL of freshly prepared modified M9 media fortified with 0, 0.5, 1, 5, 10, or 50 µM (final concentration) of FeCl3·6H2O. Upon cultivation at 30 °C/140 rpm for seven days, the cultures

Isolation and structure determination of a new analog of polycavernosides from marine Okeania sp. cyanobacterium

• Kairi Umeda,
• Naoaki Kurisawa,
• Ghulam Jeelani,
• Tomoyoshi Nozaki,
• Kiyotake Suenaga and
• Arihiro Iwasaki

Beilstein J. Org. Chem. 2024, 20, 645–652, doi:10.3762/bjoc.20.57

• culture medium prior to being assayed. The maximum DMSO concentration in the in vitro assays was 1%. The compounds were tested in an AlamarBlue serial drug dilution assay to determine the 50% inhibitory concentrations (IC50) [10]. Serial drug dilutions were prepared in 96-well microtiter plates

• , containing 50 μL of culture medium. Subsequently, 50 μL of a parasite suspension with a concentration of 4.0 × 104 cells/mL was introduced into each well. Cultures were incubated for 69 h at 37 °C under a humidified 5% CO2 atmosphere. After this time, 10 μL of resazurin (12.5 mg resazurin (Sigma) dissolved

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• . Finally, we evaluated the antibacterial activities of the compounds obtained in this study. As a result, only compound 3 exhibited weak activity against Staphylococcus aureus ATCC 6538 and Bacillus cereus with the minimum inhibitory concentration (MIC) of 500 µg/mL, respectively. Preterretonin A, the DMOA

• -derived counterpart of 3, displayed weaker activity against the two bacterial strains and was not active at the concentration of 500 µg/mL. Thus, the lack of the C-5′ methyl group somehow contributes to the biological activity of 3. Conclusion We employed a pathway engineering approach to create a series

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• using the same protocol as described above for Hyg17 except that a HiLoad 26/600 Superdex 200 pg size-exclusion chromatography column (Cytiva) equilibrated in 50 mM NaCl, 20 mM Tris pH 8.0 was used. Protein concentration was determined by UV absorbance at 280 nm using the calculated extinction

Synthesis of photo- and ionochromic N-acylated 2-(aminomethylene)benzo[b]thiophene-3(2Н)-ones with a terminal phenanthroline group

• Vladimir P. Rybalkin,
• Sofiya Yu. Zmeeva,
• Lidiya L. Popova,
• Irina V. Dubonosova,
• Olga Yu. Karlutova,
• Oleg P. Demidov,
• Alexander D. Dubonosov and
• Vladimir A. Bren

Beilstein J. Org. Chem. 2024, 20, 552–560, doi:10.3762/bjoc.20.47

• ) were used. 1 mL of a 2a–c solution and 1 mL of a perchlorate solution were mixed directly in the cuvette and thoroughly stirred. Hence, the working concentration of the compounds 2–c and the cations was 5.0 × 10–5 mol⋅L−1 and 1.0 × 10−5 mol⋅L−1. HRMS analysis was performed on a Bruker UHR-TOF Maxis

• after the addition of metal perchlorates (с2a 5 × 10−5 mol·L−1, сM2+ 1.0 × 10−4 mol·L−1). Job’s plot at the wavelength 429 nm, reflecting the interaction of compound 2a with Fe2+ in acetonitrile. The total concentration c2a + cFe2+ was 1.5 × 10−4 mol·L−1. Fluorescence intensity of compound 2a upon

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• pI50 values were calculated from plots of inhibition values vs test compound concentration using Model 205 of the ID Business Solutions Ltd Xlfit software suite. The FAT A binding fluorescent tracer was synthesized from (2S,4S)-4-[(2,6-difluorophenyl)methoxymethyl]-4-ethyl-2-methyl-N-(prop-2

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• faster with more Lewis basic urea substrates, (3) mixed solvents are uniquely able to enhance rates, with protic methanol and DCM identified as the best combination, and (4) kinetic isotope effects are variable depending on the concentration of protons in solution with small deuterium KIE’s at low

• concentration of deuterated species and large solvent KIE’s when performed in pure CH3OH versus CD3OD. Connections between catalyst activity and decomposition were made and a structurally interesting new bisphosphine–gold complex was isolated. Although our results do not provide conclusive evidence for or

• , Table 2, entry 4). We were not able to determine the maximum impact of added MeOH, because the rate of cyclization became too fast to be detectable by 1H NMR kinetics (t < 5 minutes). A LN-LN plot of MeOH concentration versus observed rate gives a slope of 0.7, indicating less than first order