C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• -analogue porphyrin 35. Use of the electron-donating p-tolylboronic acid (20), resulted in a 30% yield (Table 2, entry 12) again requiring an increase of catalyst loading and a change of base to K3PO4. Heterocyclic boronic acids/esters were again investigated for coupling reactivity with a consistent trend

• a magnitude of ≈0.3 Å less ruffling when compared to that of the meta-substituted porphyrin 37. In terms of meta-phenyl-substituted porphyrin 36 a contribution of ruffling is observed, but no ruffling is observed in the planar analogue. Crystal packing analysis of arm-extended para-substituted

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• particular for 4a which has demonstrated low micromolar toxicities (IC50 from 1.7 to 6 μM) against HuH-7, Caco-2, MDA-MB-468 and HCT-116 cells, with low to no action, on the other cells. Similarly, the meta-fluoro analogue 4i is active only on Caco-2, MDA-MB-468, HCT-116 and MCF7 (IC50 from 2 to 6 μM) while

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• to be confirmed by single-crystal diffraction analysis (see below) [33]. Unfortunately, trifluorinated analogue 12 was not crystalline. Thus, we removed the acetyl protecting groups and generated the corresponding p-bromobenzoate derivative 17 to obtain suitable crystalline material [24][34]. In

• = 180° is the 1C4 chair. The distortion of the chair conformation increases with the size of the halogen at C4. Surprisingly, the trifluorinated analogue is less distorted than the non-halogenated talopyranose. The meridian angle (φ) indicates the nature of the distortion. The distortion of the

• trifluorinated analogue is in a direction somewhat between an E5 conformation (φ ≈ 300°) and a OH5 conformation (φ ≈ 330°). The other trihalogenated analogues are distorted towards an E5 conformation (φ ≈ 300°). The distortion of the non-halogenated talopyranose is in the direction on an 4E conformation (φ ≈ 240

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• (40.39 ± 0.89 μM), in which the sulfur atom is directly bonded to the aromatic ring. The IC50 value is 63.48 ± 1.08 μM for compound 4. The appearance of a phenyl substituent in the thiazole ring affects negatively the antiradical ability of compound 4 compared to its unsubstituted analogue CatH2-CH2-S

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• the desired protein coverage and robustness. Still, the critical part of the process starts with the careful design of a NP analogue and selection of the proper biological system, which may include animal models, 3D tissue-organoids, or 2D cell culture. Depending on the project aim, which typically

• analogue, the DMP-tag, which in contrast to standardly used isotopic tags bearing the N-hydroxysuccinimide ester (NHS-ester) reacting with all primary amines of lysine side-chains, allows to selectively label the probe–protein conjugates (Figure 7A) [81][83]. The DMP-tag can be prepared in a six-steps

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

• regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO2-containing analogue of anticancer drug-candidate enastron (SO2 vs C=O) was obtained by using the here reported method in gram scale. We also demonstrate the reactivity of the Biginelli product in various directions – synthesis

• Supporting Information File 1). Next, we paid attention to testing the conditions we developed for the synthesis of the SO2-containing analogue 2r of potent anticancer drug enastron in gram scale (Scheme 3). Enastron is a novel dihydropyrimidine-based mitotic kinesin spindle protein KSP/Eg5 inhibitor [36

• -4,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidine-2(3H)-one/thione/selenone 5,5-dioxides and some of their derivatives. Furthermore, this methodology was successfully applied for the synthesis of the SO2-containing analogue of the anticancer drug-candidate enastron (SO2 vs C=O), and we believe a multitude

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• prolinamide-thiourea organocatalyst onto commercially available resins (JandaJel, polystyrene-divinylbenzene, and ChemMatrix) results in diminished catalytic activity, both in terms of yield and enantiomeric excess values, compared to the homogeneous analogue [117]. On the contrary, Dumesic and co-workers

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• replacements leading to novel MAO-A bioactive entities [16][17]. The brominated analogue 8 showed moderate MAO-A activity compared to the parent 2-furyl compound 7, as a result of increased polarizability. The condensed benzofuran 9 revealed submicromolar MAO-A potency, a resemblance to the indole system of 5

• importance and applications of ring-modified histidines, Sharma et al. [66] reviewed the design, synthesis, and medicinal chemistry of these motifs covering antimicrobial, antiplasmodial, CNS and anticancer applications among others. Pyrazoles: Betazole (95) is a pyrazole-like histamine analogue with H2

Oxidative fluorination with Selectfluor: A convenient procedure for preparing hypervalent iodine(V) fluorides

• Samuel M. G. Dearman,
• Xiang Li,
• Yang Li,
• Kuldip Singh and
• Alison M. Stuart

Beilstein J. Org. Chem. 2024, 20, 1785–1793, doi:10.3762/bjoc.20.157

• formed an analogue of Amey and Martin’s monocyclic trifluoroiodane 3. Preparation of monocyclic trifluoro(aryl)-λ5-iodanes Our investigation into the synthesis of monocyclic trifluoro(aryl)-λ5-iodanes began with the preparation of the key iodine(III) precursors for our oxidative fluorination protocol

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• cyclopamine. Comparing the biological results of the compound with the activity of desmethylveramiline (a des-E analogue of cyclopamine) has suggested that the rigidity of the oxetane ring is crucial for the potency of compound 7 [12]. Spiro-β-lactone steroids Beller et al. reported a selective method for

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

• isolated from Zizyphus xylopyra [33] and matches the exact mass and fragmentation of the 589.2820 m/z feature. The 555.2953 m/z feature (CAM555) appears to be a mono-methylated version of ceanothine E. Likewise, the 574.3396 m/z (CAM574) feature is consistent with a methylated analogue of homoamericine

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

• structure–activity relationships derived from the GI50 values. The presence of a nitro group at the furan moiety enhanced the activity (8d > 8m). Presumably, the nitro group made 8d the most potent analogue bearing an aromatic amide (8c, 8e, 8g, 8i, 8l–n). For the aliphatic amides, the most potent

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

• ][3][4][5]. Full inhibition of CDA leads to accumulation of toxic pyrimidine catabolism intermediates [6][7]. However, local and temporary inhibition of CDA in the liver provides a therapeutic benefit by allowing cytosine analogue-containing drugs to bypass the liver with an intact nucleobase

• cytosine deamination for A3 and CDA [50][59][60][61][62][63][64]. The fact that dZ (IIc), FdZ (IId) and diazepinone 2'-deoxyriboside (IIIb) used in the same DNA sequence had a differing inhibitory effect on individual A3 under identical conditions means that the structure of the cytidine analogue

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

• viruses and plays a crucial role in viral RNA replication. In the proteome of SARS-CoV-2, the catalytic subunit nsp12, expressed together with the cofactors nsp7 and nsp8, constitutes the RdRp [8]. RdRp is usually targeted by nucleotide analogue inhibitors (NAIs) [9]. This class of antivirals can inhibit

• , and they also compete with the intracellular pool of natural nucleoside triphosphates (NTPs). Nonnucleotide analogue inhibitors (NNAIs) do not face these challenges as they bind to both active but also allosteric sites of the RdRp, and therefore they represent a promising NAI alternative [12]. Since

• against SARS-CoV-2 RdRp. The RdRp was prepared recombinantly, and the inhibitory activity was measured using a primer extension polymerase assay. This assay was also used to determine the IC50 values (Figure 2 and Figure S2, Supporting Information File 1). The benzoxazole analogue 2 was devoid of any

(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

• polysubstituted BCHs, as shown by Walker and co-workers in their synthesis of tri- and polysubstituted BCHs. These include 1,2,4-BCH 191, which they described as a saturated analogue of fendizoic acid [34]. The previously discussed samarium-catalysed synthesis of BCHs (Scheme 3) reported by Procter and co-workers

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

• that the only difference between compounds 3 and 2 is the position of the hydroxy group [28]. Analyses of the NMR data of compound 4 concluded that it is an analogue of 2. In comparison with 2, compound 4 has a ketone carbonyl signal at δC 219.1 and we finally confirmed its structure by comparing it

Evaluation of the enantioselectivity of new chiral ligands based on imidazolidin-4-one derivatives

• Jan Bartáček,
• Karel Chlumský,
• Jan Mrkvička,
• Lucie Paloušová,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2024, 20, 684–691, doi:10.3762/bjoc.20.62

• group). The copper complex bearing a ligand with trans-trans configuration (Ia) is less enantioselective than those bearing a bidentate ligand analogue (87–96% ee, see [5]). Interestingly, the introduction of a methyl group at position 2 of the imidazolidin-4-one ring, i.e., ligand IIa, led to an

• yields, the reaction time could be extended. Nevertheless, the ee values obtained by catalysts of IIIa vary in the range of 84–96%; hence its enantioselectivity is comparable with the pyridine analogue [5]. Notably, the complex of ligand IIIb having cis-configuration is more enantioselective than the

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

• cyclases responsible for DMOA-derived compounds. To achieve this goal, we first aimed to establish a production system for the 4-desmethyl analogue of (6R,10′R)-epoxyfarnesyl-DMOA methyl ester by utilizing the polyketide synthase FncE, the prenyltransferase FncB, the O-methyltransferase InsA1, and the FAD

• Information File 1; CCDC: 2300693). The A. oryzae transformant with ausL yielded two products 4 and 5. The major product 4 was identified as the C-5′ desmethyl analogue of protoaustinoid A and thus named 5′-desmethylprotoaustinoid A (Figure 2C) [17][22]. Meanwhile, the minor product 5 was determined as the C

• Supporting Information File 1; CCDC: 2300694). Interestingly, compound 5 was also detected as a major product from the A. oryzae transformant harboring insB2, whereas the desmethyl analogue of the original InsB2 product [19], 5′-desmethylinsuetusin B1 (6) (Figure 2C), was only obtained as a minor product

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

• diphenyl analogue 17f was isolated as a side product upon arylation with B(C6F5)3, debromination was only observed in traces. Both aminoboranes 17d and 17e were then cleaved separately in clean conversions using formic acid to afford the desired substituted 6-bromo-5-(2-tolyl)-2,3-dihydrothiazolo[4,5-b

• marginal effects against ALOMY_R and LOLSS_R. Whilst 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 7c and 13b showed weak to moderate efficacy against ALOMY_R (strongly dependent on the application rate), o-fluorophenyl analogue 7b exhibited strong control of this resistant, commercially important grass weed

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• thiepine precursor 3a exhibited a mass decrease at 300 °C in agreement with the expected elimination of sulfur to yield almost quantitatively the corresponding PBI 6a. Its sulfoxide analogue 4a exhibited higher thermal reactivity, with the loss of SO identified at lower temperature (225 °C). As a proof of

• photoextrusion of S and SO2 fragments are classical methods in organic synthesis [54][58][59], whereas photoextrusion of SO from bisaryl sulfoxide moieties has been evidenced more recently by Wolf et al. [60][61]. Solutions of dinaphthothiepine 3a and its sulfoxide analogue 4a in dichloromethane were irradiated

Synthesis of the 3’-O-sulfated TF antigen with a TEG-N₃ linker for glycodendrimersomes preparation to study lectin binding

• Mark Reihill,
• Hanyue Ma,
• Dennis Bengtsson and
• Stefan Oscarson

Beilstein J. Org. Chem. 2024, 20, 173–180, doi:10.3762/bjoc.20.17

• Mark Reihill Hanyue Ma Dennis Bengtsson Stefan Oscarson Centre for Synthesis and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland 10.3762/bjoc.20.17 Abstract The synthesis of gram quantities of the TF antigen (β-ᴅ-Gal-(1→3)-α-ᴅ-GalNAc) and its 3’-sulfated analogue with a

• -3, TEG-N3 glycosides of the TF antigen (β-ᴅ-Gal-(1→3)-α-ᴅ-GalNAc, 1) and its 3’-O-sulfated analogue (2, Figure 1) were required on a gram scale to allow efficient synthesis of the glycodendrisomes. The TF antigen is presented on the surface of most human cancer cell types and its interaction with

• galectins 1 and 3 leads to tumour cell aggregation and promotes cancer metastasis [3][4][5]. The 3’-O-sulfated analogue is known to bind to siglecs 1, 4, and 8 [6] as well as galectin 4 [7][8], but its biological role is not that well investigated. Compound 2 is a new compound but two syntheses of compound

Aldiminium and 1,2,3-triazolium dithiocarboxylate zwitterions derived from cyclic (alkyl)(amino) and mesoionic carbenes

• Nedra Touj,
• François Mazars,
• Guillermo Zaragoza and
• Lionel Delaude

Beilstein J. Org. Chem. 2023, 19, 1947–1956, doi:10.3762/bjoc.19.145

• compound 6e belonged to the P21/c space group. A comparison of the C1–S1 and C1–S2 distances recorded in the four crystal structures under scrutiny and those determined previously for 1,3-dimesitylimidazolium-2-dithiocarboxylate (IMes·CS2) and its more saturated analogue SIMes·CS2 showed that the negative

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• with a diazo reagent under neutral conditions may give rise to a separate regioisomer which is different from the product obtained by reaction with an alkyl halide under basic conditions. Recently, we designed a thalidomide analogue 1a in which the phthalimide moiety was replaced with benzotriazole

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

• (hdz-NO2). It is expected that those substituents impact the chemical (e.g., acidity and hydrolysis susceptibility) as well as the structural and spectroscopic properties of the compounds. Results and Discussion The methyl-substituted hdz-CH3 and its nitro-containing analogue hdz-NO2 were isolated as

Quinoxaline derivatives as attractive electron-transporting materials

• Zeeshan Abid,
• Liaqat Ali,
• Sughra Gulzar,
• Faiza Wahad,
• Raja Shahid Ashraf and
• Christian B. Nielsen

Beilstein J. Org. Chem. 2023, 19, 1694–1712, doi:10.3762/bjoc.19.124

• study raises a concern regarding the performance of dyes with tert-butyl substituted DPQ acceptors, either containing benzene (Qx74) or thiophene (Qx75) as a π-conjugation linker and their benzotriazole analogue. While the incorporation of the Qx enhances the interaction between the donor and acceptor