Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• thermostable components of functional organic materials. Keywords: molecular hybridization; nitric oxide; nitrogen heterocycles; 1,2,5-oxadiazoles; 1,2,3-triazin-4-one; Introduction Nitrogen heterocycles are a significant and broad class of organic substances included in the structure of various natural

• , indicating that the developed tandem protocol does not depend on the presence of the N-oxide moiety in the parent heterocycle. All synthesized triazinones 1 and 7 were fully characterized by IR, 1H and 13C NMR spectroscopy, and high-resolution mass spectrometry. The structure of compounds 1b and 7h was

• physiological conditions. Moreover, the target bicyclic compounds were shown to be thermostable substances and could be used in various fields of materials science. Examples of bioactive compounds containing the 1,2,3-triazin-4-one core. The X-ray structure of compound 1b (CCDC 2363621) and 7h (CCDC 2363622

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

• -crosslinker, is attached synthetically to the basic scaffold (Figure 2A) [28][29][30][31][32]. However, this requires a structure–activity relationship (SAR) screening to ensure that the selected NP retains biological activity after modification. The term probe is further used to unite such NPs and active

• , in this case, the cysteine thiols were derivatized and the cysteine C–S bond was previously described to be susceptible to fragmentation, the fragments containing the thiol provide the information on the structure of the modified amino acid side chain [107][108]. Although the study was focused on the

• commonly used proteases [109]. Multiple modifications to the peptide sequence and linker structure were consecutively introduced by the Cravatt lab including the ‘light’ and ‘heavy’ derivatives containing stable isotopes enabling the quantification and direct comparison between the conditions [80]. The

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

• guanidine motif in AA-3 compared to simple AA-1. Alterations in the thiol structure within thiomalonates significantly impact their stability and reactivity, thereby influencing both reaction efficiency and stereochemical outcome, as demonstrated in the case of catalysis employing bifunctional hydrogen bond

• stereoselectivities requiring only 1 hour instead of 45 and 70 hours. Unfortunately, attempts to add thiomalonate 3 and dibenzyl malonate failed. In the first case, instead of forming the expected product, only the thiophenol adduct is formed (see Scheme 2, right chart, for the structure of sulfa-Michael adduct; R

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• the generality of H-bond activation of iminoiodinanes for direct aziridination, albeit with modest efficiency for some substrates. The impact of the iminoiodinane structure on the efficiency of HFIP-promoted direct aziridination was next investigated (Scheme 3). For this purpose, cyclopentene was

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

• ]. Despite the prominence of organocatalytic reactions, catalyst development has so far mostly been conducted guided by intuition of skilled organic chemists. Given that organocatalytic reactions are governed by different competing interactions, the influence of a change in molecular structure is often non

• data needs to be provided in a machine-readable way. Unlike chemists who typically use drawings of Lewis structures to represent molecules, computers require a numerical representation of the molecular structure. Since the information that describes the input directly influences what relationships a

• successfully applied for predictive modelling in organocatalysis. In contrast to the representations through graphs, or SMILES, which can be directly obtained from the molecular structure, the selection of appropriate descriptors is problem-specific and requires knowledge about the fundamental interactions

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• structure of DAntM radical (left) and its spin delocalization on two anthryl units. (b) Plausible head-to-head σ-dimerization of the DAntM radical. (a) ESR spectrum of the DAntM radical (black line, Exp.) and its simulated pattern (red line, Sim.). (b) Hyperfine coupling constant of the DAntM radical. (a

• ) ESR spectrum of anthroxyl radical 5 (black line, Exp.) and its simulated pattern (red line, Sim.). (b) Hyperfine coupling constant of 5. (c) X-ray structure of 5. Hydrogen atoms are omitted for clarity. Cyclic voltammogram (CV) of DAntM cation. (a) CV measured with scan rate at 3.0 V s−1. (b) Scan

Metal-free double azide addition to strained alkynes of an octadehydrodibenzo[12]annulene derivative with electron-withdrawing substituents

• Naoki Takeda,
• Shuichi Akasaka,
• Susumu Kawauchi and
• Tsuyoshi Michinobu

Beilstein J. Org. Chem. 2024, 20, 2234–2241, doi:10.3762/bjoc.20.191

• -ethynyltriazole derivative (out-) (6b) adducts were formed. To determine the chemical structure of the product, the NOESY measurement was conducted. The NOESY spectrum suggested the intermolecular through-space coupling between two benzene protons (Figure S10 in Supporting Information File 1). This result

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• reaction was expected, Figure 2) with morpholine under previously found conditions (Scheme 2). To our delight, the meta-1,2,4-oxadiazole aniline 3ab, formed by the sequence of aldol-type reactions, was isolated in 80% yield and its structure was confirmed by NMR and single crystal X-ray analysis (CCDC

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• fungi, are discussed with view on their isolation, structure, biological activities, biosynthesis, and total syntheses. This class of compounds consists until now of 127 naturally occurring compounds, with very divers structural motifs. Although only a handful of these toxins (i.e., alternariol and its

• respective chapters: A quinone structure has been given with the first report of botrallin [36], but was corrected some years later [37]. A wrong constitution has originally been proposed for altenuene [38]; it was revised shortly after [39]. The originally proposed structure [40] of altenuisol is wrong

• : Total synthesis and comparison of the NMR spectra revealed that this natural product is identical with altertenuol [41], whose structure was correctly given previously [42]. Furthermore, the originally proposed structures [43] of graphislactones E and F were corrected after total synthesis and

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• electron transfer processes etc. [26][27][28]. On the other front, doping with heteroatom(s) to the truxene skeleton drastically modulate its unique physical as well as chemical properties besides the geometrical structure, as well [29]. After successful construction of truxene and its asymmetrical isomer

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• insufficient to support the accurate training of data-hungry machine learning models [10][11] and thereby leading to potentially sub-optimal experimental design due to an incomplete understanding of the underlying structure–activity relationship and poor calibration of predictive uncertainty. Additionally

• combinatorial expansion of training data (Supporting Information File 1, Figure S3), these extra datapoints benefit the deep models’ abilities to learn the underlying structure–activity relationships more accurately and readily identify the most potent compounds of interest with novel scaffolds. In addition, as

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

• products and publications as analyzed by Reaxys database. The search was performed using depicted substructures “on all atoms” (May 2024). Distribution of compounds 2a–r, 3–7 (log P (y)–MW (x)) through LLAMA software. The chemical structure of a representative compound 2m is shown. The general Biginelli

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

• , the electrostatic interaction between the homogeneous catalyst and the support is robust enough to reduce leaching significantly [67][73]. However, a potential drawback of this technique is that the presence of a charged support can lead to complications, such as distortion of the catalyst structure

• solid support may impose restrictions on access to the active sites of the organocatalyst. If the active sites are too close to the support backbone or situated within the porous structure of the support, they are less accessible for larger reactant molecules, thereby affecting the catalytic activity

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• is a promising synthetic reagent not only as a one-carbon homologation reagent but also as a nitrogen source for nitrogen-containing molecules. Because of their isoelectronic structure with carbon monoxide, isocyanides also react with nucleophiles, electrophiles, carbon radicals, and transition metal

• reaction, pressurization in an autoclave or other pressurization device is required to increase the CO concentration. Isocyanides, on the other hand, have an isoelectronic structure with carbon monoxide and are expected to be not only a promising C1 resource but also an important synthetic reagent for

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

• physical functions [3]. Glycoscience encompasses the comprehensive study of glycans focusing on their structural, biosynthetic, biological and evolutionary aspects [4], thus playing a central role in the identification and characterisation of the glycome’ structure and function, and in unveiling its

• , especially in bacterial glycans, makes the structural and conformational analysis of glycans extremely difficult, posing a considerable challenge when employing conventional structural biology methods for glycan analysis [10][12]. Nevertheless, understanding the three-dimensional structure of glycans is

• -known family of GBPs is constituted by the lectins, ubiquitous receptors that exhibit the ability to specifically recognise different carbohydrates through their well-defined binding pocket and they conserved three-dimensional structure similarities [32]. On the other hand, GAG-binding proteins, which

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

• . At the first stage, submicron colloidal particles based on carboxymethylcellulose and chitosan with a domain structure were obtained in an aqueous suspension. In the second stage, the Ugi reaction was carried out on the surface of the Pickering emulsions with toluene. Removal of toluene and

• the formation of a double Pickering emulsion using a microfluidic technique. Solidification of this structure and removal of the template resulted in the formation of nonspherical capsules with large openings [13]. The use of a polymer matrix that can swell in an organic solvent made it possible to

• ]. However, the relationship between the structure of the initial particles and the surface morphology of colloidosomes is not yet understood clearly enough. Quite often, there are cases where the number of colloidal particles is clearly insufficient to cover the surface of the droplets observed in stable

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -phenyl-3,5-substituted pyrazoles 148 (Scheme 51) [156]. Efforts to synthesize bridged pyrazoles using fumaryl chloride proved unsuccessful, with only 3,5-substituted pyrazoles isolated. Nonetheless, the crystal structure of such a pyrazole was investigated [157]. In their study, Alizadeh et al. showed

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• considerable interest in the stereoselective synthesis of the cyclohexanone skeleton as it constitutes the core structure in many natural products and pharmaceutical drugs [1][2]. Garsubellin A with a cyclohexanone skeleton is a potent inducer of choline acetyltransferase (ChAT) and could be used for the

• undergoing yet another diastereoselective 6-endo-trig intramolecular oxa-Michael addition. The structure and stereochemistry of compounds 3 and 4 were confirmed by 1H-1H-COSY and 1H-1H-NOESY NMR experiments. This was further unambiguously established by single crystal X-ray analysis of a representative

• reported in due course. Biologically active derivatives of cyclohexanones. X-ray structure of 4a (CCDC 2351387). Origin of stereoselectivity in the double Michael addition. The Michael donor–acceptor reactivity of curcumin: previous vs present work. A plausible reaction mechanism. Scale-up reaction

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

• azobenzene (Azo) or, more recently, arylazopyrazoles (AAPs), which change shape and polarity on photoisomerisation between the E and Z states, thus changing the self-assembled structure. Small-angle X-ray scattering (SAXS) is a powerful technique to probe the morphology of PS and can be used to measure the

• spatiotemporal control. To build responsive materials, surfactants are particularly attractive due to their ability to self-assemble into different morphologies depending on their molecular structure and chemical environment. To that end, photoswitchable chromophores can be incorporated into amphiphilic

• is a powerful technique that can be used to determine the structure and interactions of materials on length scales of 1–100s of nm. As a result, it has been used to study the changes in self-assembled morphologies of PS on irradiation with light [4][21][22][23][24][25]. In particular, the high

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

• methylenes (δC 25.0–44.8), and two magnetically equivalent tertiary methyl groups (δC 29.5/δH 1.13). These molecular parts accounted for four degrees of unsaturation out of five, leaving one degree for a ring structure. In addition, a highly conjugated functional group was suggested by UV maximal absorptions

• provided a methoxycarbonyl (–COOMe) fragment. Finally, this fragment was placed at C2 by an HMBC correlation from H5 to C6 to complete the gross structure of 1. Both compounds 2 and 3 were obtained as greenish yellow amorphous and their molecular formula were suggested to be the same as that of 1 from

• 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

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• radicals derived from azo radical initiators. The radical selectively attacked the distal α-position relative to the meso-position to construct a nonaromatic bowl-shaped structure. The photophysical and electrochemical properties of the obtained radical adducts were compared to those of the parent Ni(II

• toluene (Scheme 1). The reaction smoothly proceeded to afford dialkylated macrocycle 2a in 92% yield. In addition to 2a, monoalkylated product 3a and dipyrrin dimer 4a were obtained as minor products in 4% and 3% yield, respectively. The structure of 2a was unambiguously confirmed by single-crystal X-ray

• analysis, which revealed that two alkyl substituents were located on the same side of the molecule (Figure 2a). Compared to the planar structure of 1 (Figure 2b) [2], 2a displays a nonplanar structure due to the sp3 carbon atoms adjacent to the nitrogen atoms. The 1H NMR spectrum of 2a confirmed that the

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• amino group by reduction. We reasoned that increasing the sp2 fraction and the rigidity of the whole structure will lead to increased stability of these derivatives. The first exploratory attempts demonstrated the easy preparation and the high bench stability of the oxime derivatives, therefore we opted

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

• ); isoquinolinone; solvent-dependence; Introduction Isoquinolinone is an important heterocyclic structure found in many natural products and biologically active compounds, including pharmaceuticals [1]. For instance, lycoricidine, found in the medicinal plant Lycoris radiata, may inhibit the MCPyV LT protein

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• diaryldihydrophenazine was increased (10%). Thus, protonation completely suppressed the intramolecular cyclization route. Heterocyclic salts S1–S3 were obtained as amorphous solids, soluble in polar solvents (acetonitrile, DMF, acetone) and chlorinated hydrocarbons (CHCl3, CH2Cl2). The structure of new N

Access to 2-oxoazetidine-3-carboxylic acid derivatives via thermal microwave-assisted Wolff rearrangement of 3-diazotetramic acids in the presence of nucleophiles

• Ivan Lyutin,
• Vasilisa Krivovicheva,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 1894–1899, doi:10.3762/bjoc.20.164

• two diastereomers, lying in the intervals 5.5–6.0 Hz and 1.5–2.5 Hz for the cis and trans forms, respectively [33][34]. This makes it easy to assign the stereochemistry of the products obtained. Additional confirmation was gained from X-ray analysis data for structure 3t (Scheme 2). In some cases, we