Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• ]pyrrole α,β-isomer 4 was found to be catalytically active providing a 57% conversion to 10, suggesting a concerted cycloaddition mechanism. Calix[4]pyrrole α,α-isomer 3 and dipyrromethane 5 were catalytically inactive. The authors concluded that the catalytic inactivity of 3 is caused by the parallel

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• backbone adopt a nearly parallel orientation with a slight tilt compared to the horizontal axis which results in one short (Figure 3a, left ligand: 2.2 Å, and right ligand: 2.3 Å) and one longer Htriazole···Hquinolate (Hg···Ha) distance (left ligand: 2.8 Å, and right ligand: 2.8 Å). Contradictory, the

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• hypervalent R–I–X bond and the plane of the arene substituent (Figure 3c): When the plane of the arene ring was parallel to the R–I–X bond (φ < 5°), relatively stable compounds ensued, while a large twist away from planarity resulted in compounds that were destabilised towards thermal decomposition. For

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

• and breast carcinoma MCF7. In parallel, human skin fibroblasts were used as reference for non-tumor cells and roscovitine (ROSCO), doxorubicin (DOXO) and Taxol as positive controls. For details see: ref. [2] and Supporting Information File 1, Table S1. Compounds 4a–f, 4h, 4i, 4k, 4l, 4o and 4q that

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

• clearly arise from repulsion of the axial fluorine at C2 and the axial halogen at C4 as exemplified with the H3–C3–C2–F2 and the X4–C4–C3–H3 torsion angles being smaller than the expected 180° (Table 3, entry 16 and 17). The 1,3-diaxial repulsion leads to a deviation from parallel alignment as shown in

• Table 4. The Newman projections of the halogenated analogues show deviations from parallel alignment for the C2–F and C4–X substituents of 12.08° for 17, 17.08° for 13, 18.18° for 14, and 18.59° for 15 (talopyranose, 18: 5.92°). This deviation is responsible for the distance between F2 and the halogen

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

• disease [2][3]. In parallel, mass spectrometry (MS) has been crucial in many areas centered around the characterization of NPs [4]. First to annotate their often complex structures using diverse fragmentation techniques [4]. Nowadays, MS is applied for the identification of NPs’ cellular protein targets

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• also the structure for which the descriptors are considered. This can either be ensured by expert-knowledge of preselecting relevant structures, for example based on a known mechanism, or by considering information from the entire conformer ensemble. Parallel to the evolution in modelling steric

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• ) [43]. In parallel, Sheng and Zhang et al. found that 2-(1,3,4-oxadiazol-2-yl)aniline derivatives 38 could be electrochemically synthesized from isatins 35 and acylhydrazine 36. The transformation was carried out in an undivided cell at high temperature in DMSO using potassium iodide as supporting

• electrolyte ammonium acetate and the alcoholic solvent acted as N and C1 sources, respectively. The authors proposed the mechanism depicted in Scheme 10. The deprotonation of hydrazone 52 afforded anion 54 which underwent SET anodic oxidation to form radical 55. In parallel, an elusive oxidation of alcohol

• oxidation of N-arylhydrazone by electrogenerated iodide radical (Scheme 11) [50]. In parallel, the group of Yuan achieved the electrosynthesis of 1,3,5-trisubstituted 1,2,4-triazoles 67 from arylhydrazines 64, aldehydes 65 and primary amines 66. Iodine-mediated electrooxidation of in situ-generated aldehyde

Allostreptopyrroles A–E, β-alkylpyrrole derivatives from an actinomycete Allostreptomyces sp. RD068384

• Marwa Elsbaey,
• Naoya Oku,
• Mohamed S. A. Abdel-Mottaleb and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2024, 20, 1981–1987, doi:10.3762/bjoc.20.174

• and 3, their conformational ensembles, datasets of a structure and population of each conformer [25], were determined using a Spartan 24 parallel package conformational search tool (Wavefunction Inc, USA), followed by geometry optimization of the most weighted conformers (Boltzmann distribution weight

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

• allow the reaction to take place under the mildest possible conditions. This search goes in parallel with the urge to use increasingly diverse and complex building blocks, up to and including DNA conjugates, which would be degraded under the classical conditions developed by Groebke, Blackburn and

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

• stereoselective cyclization reactions. This review aims to provide an overview of these approaches and parallel comparisons with original biosynthetic pathways by highlighting five examples of chemo-enzymatic total syntheses of natural products reported since 2017. The examples are the synthesis of cotylenol (1

• aromatization provides chalcone 43. Prenylation of the resultant aromatic ring of 43, catalyzed by MaIDT (Morus alba isoliquiritigenin 3-dimethylallyltransferase), leads to morachalcone A (44) [50][51]. In parallel, benzofuran 46 was biosynthesized from 4-coumaroyl-CoA via thioester 45. Further prenylation of

• classification, along with parallel discussions of the original biosynthetic pathways, helps organize the current state of the art and offers a comprehensive overview of how synthetic methodologies leverage the natural biosynthetic pathways. The development and optimization of chemo-enzymatic synthetic processes

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• . Kukhar Institute of Bioorganic Chemistry and Petrochemistry, Akademik Kukhar Street 1, Kyїv 02094, Ukraine 10.3762/bjoc.20.143 Abstract Parallel Groebke–Blackburn–Bienaymé reaction was evaluated as a source of multimillion chemically accessible chemical space. Two most popular classical protocols

• last two decades, the GBB reaction has been studied in more than 200 research papers [21] and a number of works (including the original publication by Blackburn and coauthors [20]) described its parallel synthesis version [24][25][26][27][28][29]. Recently, we have shown that other (pseudo-)three

• the corresponding library members were denoted as 4{i,j,k}. Results and Discussion Library synthesis Preliminary experiments on the parallel GBB reaction were performed with heterocyclic amines 1{1–430}, aldehydes 2{1–583}, and isonitriles 3{1–73} available from our stock (based on our previous in

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

• points, in which XB donors with larger Vs,max values also had more exergonic associations, we actually observed two almost parallel clusters of data (Scheme 6c). In this case, neutral XB donors 26–28, and 30–36 had Vs,max values ≈5–50 kcal/mol and a slope of −0.24 (Scheme 6c, light grey dots), whereas

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

• , promoting, via hydrazone–enamine tautomerization [17][24][25], the nucleophilic addition which concludes with the construction of the heterocyclic N,O-aminal 5 through the intramolecular N–C bond formation. The FeCl3 can also interact with the newly formed N,O-aminals 5, giving rise to the second parallel

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• corresponding ESP maps. A comparison of the ESP maps of 3a and hydrocarbon [6]CMP showed induction of biased densities by the nitrogen dopants. Similar biased densities were previously found to be critical in determining the packing structures of nitrogen-doped π-systems to make parallel-displaced

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

• as a cofactor [10][11][12][13]. The parallel behavior of Flu17 and AlpJ in the reaction with 8 provides additional support for the shared oxidative B-ring cleavage and contraction steps in the biosynthesis of fluostatins and kinamycins. Nevertheless, the mechanism by which a B-ring-contracted

Monitoring carbohydrate 3D structure quality with the Privateer database

• Jordan S. Dialpuri,
• Haroldas Bagdonas,
• Lucy C. Schofield,
• Phuong Thao Pham,
• Lou Holland and
• Jon Agirre

Beilstein J. Org. Chem. 2024, 20, 931–939, doi:10.3762/bjoc.20.83

• validation report can be generated for each carbohydrate in the molecular model. This report is put out in JSON format for easy consumption by web-based database frontends. The initial report generation was completed in parallel over 64 CPU cores in around 5 h. After the initial surveys through PDB and PDB

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• that the distance between the molecules within the unit cell is higher than the distance between the unit cells. In addition, the molecules are arranged parallel-displaced to each other, which is considered to be more stable than the sandwich arrangement [64][65][66][67][68]. Consequently, the distance

• between the layers varies periodically between 3.373 Å and 3.662 Å. This results in different interactions between the layers, as depicted in Figure 3. Furthermore, the layers are arranged in an anti-parallel face-to-face order to reduce the steric hindrance. Within the shorter distance layers (3.373 Å

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

• a parallel direction, as the bulky -OMe groups are located outside the tweezer’s cavity to avoid steric hindrance with each other. When protonated, the pyridinium group acts as a hydrogen-bond donor for the two methoxy groups and triggers the rotation of the respective benzene rings along with the

• release of siRNA or miRNA encapsulated within them into the solution in vitro and in vivo [21]. The closed conformation of 2 with parallel alkyl chains acts as a building block of the bilayer membrane and is packed together with other lipids. When the surrounding medium becomes acidic, the tweezers adopt

• arms with planar Pt complexes are parallel and the distance between them allows for the intercalation of another terpy-Pt complex. The guest intercalation coupled with the induction of short-range Pt–Pt interactions was followed by UV–vis absorption and emission spectroscopies with characteristic MMLCT

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• anionic 1a–i-enolate species in parallel with N-fluoroammonium ion 6. Fluoride ions formed through the reactions between fluorine and quinuclidine or fluorine and enolate species, may deprotonate 1a–i-enol, to form enolates of 1a–i that are reactive towards both fluorine and N-fluoroammonium ion 6. The

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• transition corresponds to the CT band. The structure and stability of [10]CPP⊃[5]CPP2+ were estimated by DFT calculations at the ωB97-XD/6-31G* level of theory. Three isomeric structures were optimized, of which complex 1, with two CPPs aligned in parallel, is the most thermodynamically stable (Figure 5a

• ). Furthermore, the tilting of the complex in adjacent columnar structures with respect to the short axis is opposite to each other, as in a herringbone structure, and such columnar structures are parallel to each other through a columnar structure consisting of a host–guest complex in blue and its counterions

• . On the other hand, the complex in blue forms a 1D columnar structure with alternating counterions (Figure 7g), and each column is parallel to the others. Furthermore, the complex is tilted at approximately 30° relative to the long axis of the unit lattice. Conclusion [10]CPP encapsulates [5]CPP2+ in

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• conditions (Scheme 25A). The general catalytic cycle begins with oxidative addition of an organohalide into a Ni0 catalyst yielding NiII complex 125 (Scheme 25B). In parallel, the initial SET activation of RAE 10, leading to the formation of radical anion 11, takes place in the presence of a stoichiometric

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• ). In parallel, we also expressed CMA1 in a bacterial expression system, which allowed us to ascertain whether binding was influenced by lectin glycosylation. The full-length mature protein (6–264) and individual N- or C-terminal domains were expressed using a N-terminal fusion comprising DsbC and a

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

• pristine acene with a dienophile to transiently form a cycloadduct with increased solubility for processing purposes, and unmasking it afterwards via a retro-Diels–Alder reaction [16][17][18][19]. In parallel to retro-Diels–Alder reactions, another efficient strategy for the in situ aromatization of target