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

• pharmacological properties and may find application in the design of new promising medications. Herein, we present a convenient synthetic approach for the preparation of previously unknown [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-one heterocyclic systems containing both a furoxan/furazan fragment condensed to

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

• identification rates and may help to identify otherwise difficult to find interactions between active compounds and proteins, which may result from unperturbed conditions, and thus are of high physiological relevance. Keywords: chemical proteomics; diagnostic ions; mass spectrometry; target identification

• spectrometry-based chemical proteomics represents a robust method for the identification of NP protein targets, in some cases, the synthetic effort associated with the above-described SAR study to find a functional NP probe might outweigh the advantages of this approach. Considering a complementary strategy

• -improving search algorithms to find a new features and probe–protein interactions. Automatization of chemical proteomics workflows The increased throughput and less hands-on time during the chemical proteomics workflows led recently to a number of protocols, which either multiplicate the sample preparation

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 potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• ), Koser’s reagent (PhI(OH)OTs), Zhdankin’s reagent (C6H4(o-COO)IN3, ABX), and Dess–Martin periodinane (DMP) – and find application in an array of synthetically important transformations including olefin difunctionalization, carbonyl desaturation, alcohol oxidation, and C–H functionalization [3][4

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

• transferable reactions The key to modelling transferable reactions together is to find a representation that can describe all relevant reacting species. While such representations commonly exist in chemistry, e.g., SMILES and graphs, the most common representation for transferable reactions is via expert

• catalysts’. While the concept of generality was recently explored in a closed-loop fashion for Suzuki–Miyaura cross couplings to find the most general catalyst and reaction conditions [131], the application of this concept in the context of ML has found comparatively less attention in organocatalysis

• training set was constructed consisting of 18 catalysts. Subsequently, the enantioselectivity of each catalyst with 13 model substrates was experimentally evaluated. 13 different models, one for each substrate, were developed. To find a general catalyst, a technique termed ’catalyst selection by committee

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

• these clusters to rapidly identify potent inhibitors. In contrast, Chemprop was more targeted at the beginning and exploited the one cluster where it could find potent inhibitors (Figure 3B). After that, Chemprop traveled more broadly and was not able to identify all clusters of potent inhibitors even

• . XGBoost initially showed more targeted behavior where it exploited one cluster and then broadly searched during 16–30 iterations to discover another relevant cluster (Figure 4B). Random Forest immediately exploited the one cluster where it could find potent inhibitors, but after searching more widely it

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

• ). However, increasing acidity and using trifluoroacetic acid (Table 1, entry 17) did not improve the overall yield. We also tried microwave activation conditions since this is a known technique for reactions of this type [32], but unfortunately, we did not find any improvement in the yield (Table 1, entry

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

• ], pyrazoles also find applications in OLED technology [20] and optical brighteners [21] in the textile and laundry industry. The ongoing quest for novel, potent, and efficient syntheses of pyrazoles prompts the search for the “ideal” synthesis [22][23], one that addresses all the synthetic challenges to meet

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

• -metal-based transformations. However, their use is significantly hampered by their inherent instability and hazardous nature. Therefore, it is endlessly highly demanding to find a new mode of generation of diazo compounds from stable and safe precursors. The third part of this review is dedicated to

• hydrazones, coupling with other partners or examination of different hydrazones, such as trifluoromethylated hydrazones, should enable the straightforward access to diversely functionalized molecules. Hopefully, this review will stimulate further development in this area which could eventually find useful

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• . Photochemical [2 + 2]-cycloaddition with fluorinated aldehydes and ketones gives access to a variety of fluorinated oxygen-containing heterocycles. We hope that this article will help chemists to utilize HFO-1132 and that this olefin will find applications as a useful synthon in organic chemistry. 1,2

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• precursors of alkylating reagents presents an opportunity to find new ways to diversify indazole reactivity by simple modifications of reaction conditions. Mechanistic understanding would allow for further diversification in related systems. The indazole ring presents annular tautomerism regarding 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

• , while also holding a crucial function in many biological processes [8]. Non-canonical amino acids (NCAs) are widely used in medicinal chemistry [9]. Not surprisingly, they also find broad use as bifunctional building blocks (BBs) for DELs. In an early example, an 800-million-members DEL utilized Fmoc

• continuous flow conditions, leading to reaction completion within 30 minutes (Scheme 4). Oxime formation Once the ethyl heteroarylacetates scope was completed we turned our attention to the incorporation of the amino group. There are precedents for α-aminations, but we were not able to find a method suitable

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

• corresponding to 2 F per mole of amine A1 was passed through the solution, the targeted salt S1 was isolated in a promising 45% yield (Scheme 4). To find the optimal conditions, a base (2,6-lutidine) was added in the reaction mixture. A base is required to bind a proton released in the diarylamine oxidation

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• purification. Thus, it significantly improves existing approaches. Keywords: catalysis; deazaalloxazine; flavin; multicomponent approach; one-pot reaction; Introduction Heterocyclic compounds containing pyrimidine and quinoline motifs in their structure, both of natural and synthetic origin, find a wide set

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• PASs, it is unlikely to find actual “sphere”-like molecules, as the individual building blocks have rigid and planar geometries and fusing such components together in a cata-condensed fashion is unlikely to generate molecules with a spherical structure. Rather, for our dataset, the 3D-type molecules

• contrast, for all the B- and N-containing heterocycles, the respective regions are quite broad and without a well-defined shape, meaning that it is possible to find molecules with different combinations of low/high/mid-range HOMO and LUMO values within the region. Overall, it is apparent that the

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• lichenicidin A1 [48], FlvA.1 [42], FlvA.2 [42], BhtA α [49], SmB β [50], Smb α [50], and thusin β [47] (Figure 3B). We find that, especially in the first 20 amino acids of the alignment or the first half of the mature peptide, there are significant sequence differences. Of particular interest, cellulosin forms

Ugi bisamides based on pyrrolyl-β-chlorovinylaldehyde and their unusual transformations

• Alexander V. Tsygankov,
• Vladyslav O. Vereshchak,
• Tetiana O. Savluk,
• Serhiy M. Desenko,
• Valeriia V. Ananieva,
• Oleksandr V. Buravov,
• Yana I. Sakhno,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2024, 20, 1773–1784, doi:10.3762/bjoc.20.156

• the double bond are trans configured. To find out the patterns of the new reaction, we applied different conditions to a wider range of starting bisamides 5–8 (Table 2). As in the model reaction (Scheme 3), the main products of the transformation were the corresponding amides 10a–d (Table 2). In the

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• chromatography column, while the more eco-friendly second strategy needs an additional stage for the reduction of the nitro group on the Ugi adduct. In order to find a more efficient synthesis, we thought that the second nitrogen in the diazepine nucleus could be incorporated without the need of surrogates or

A fiber-optic spectroscopic setup for isomerization quantum yield determination

• Anouk Volker,
• Jorn D. Steen and
• Stefano Crespi

Beilstein J. Org. Chem. 2024, 20, 1684–1692, doi:10.3762/bjoc.20.150

• scaled subtraction [14]. Another powerful method to obtain the spectrum of the second isomer is global and target analysis, where time-resolved spectra can be analyzed to find the number of spectral components and the evolution of their concentration over time [36][37]. Additional information, such as a

• literature to find the spectrum of cis-azobenzene [17]. To calculate the quantum yields, both the molar absorptivities of the isomers and the number of photons absorbed by the sample needs to be known very accurately. Utilizing chemical actinometers remains the most used method for the determination of

• we did not find any significant changes between the quantum yields found using the measured emission spectra and the ones provided by the vendor, it is known that small variations in the LED spectral distribution can occur per lot [53]. Conclusion In this work, we report a simple setup for the

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• -, and λ-carrageenans (Figure 5) [28]. Carrageenans find utility in drug and food industries because of their antioxidant and antiviral activities [119][120][121]. In the sequenced genome of a marine-derived Microbulbifer thermotolerans JAMB-A94T was detected an ι-carrageenase encoded by gene cgiA [28

• -fructofuranosidase were expressed in E. coli [41]. Both enzymes can work together to effectively degrade inulin. Lipases are enzymes that can hydrolyze various fatty esters and find applications in the detergent, oil, and pharmaceutical industries. The lip4346 is a novel lipase-encoding gene cloned from the

pKalculator: A pK_a predictor for C–H bonds

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2024, 20, 1614–1622, doi:10.3762/bjoc.20.144

• values that are not correlating well with the QM-computed pKa values, we find C–H sites that are either bridgeheads or where the negative charge is stabilized by resonance. This may be due to the nature of the chosen descriptor vector based on sorted CM5 atomic charges as it may not take into account

• 21.9 (the least substituted C–H next to a ketone). For more information, see Supporting Information File 1, section “Outliers for Reaxys”. When we evaluate our ML models on the whole out-of-sample set, we again find that the regression model (MCC of 0.82) outperforms the classification model (MCC of

• 0.70) when used as a binary classifier as seen in Table 2. While a direct comparison cannot be made between Roszal et al.’s results [3] and ours, we find our result to outperform theirs with an accuracy of 0.96. In general, it is surprising that the LightGBM regressor outperforms our LightGBM

Divergent role of PIDA and PIFA in the AlX₃ (X = Cl, Br) halogenation of 2-naphthol: a mechanistic study

• Kevin A. Juárez-Ornelas,
• Manuel Solís-Hernández,
• Pedro Navarro-Santos,
• J. Oscar C. Jiménez-Halla and
• César R. Solorio-Alvarado

Beilstein J. Org. Chem. 2024, 20, 1580–1589, doi:10.3762/bjoc.20.141

• different hypervalent iodine reagents for this reaction. To find the correlations between experiments and theoretical calculations, chlorination and bromination of 2-naphthol using PIFA/AlCl3 and PIDA/AlBr3 were carried out. Consequently, we found an excellent correlation between the yield and the energy

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• metal catalysis as a viable and potentially general approach for reaction discovery and would find broad application in new synthetic contexts. Decarboxylative cyanation: background and our working hypothesis. Scope of electrophotochemical decarboxylative cyanation of aliphatic carboxylic acids. All

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• parameters. We hope that these potentially biologically active bicyclic fluoroalkoxy compounds will find a place in various application areas in biological systems. Organofluorine derived drugs. Oxyfluorination of benzonorbornadien (1a) with Selectfluor and alcohols. All reactions were carried out using 0.5

Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• sources and thus as building blocks for synthesizing pyrazolyltriazoles by CuAAC reactions. To find a feasible approach to pyrazolyltriazoles of type 1 with a highly substituted scaffold, we decided to explore the benefits of a modification of the triazene-protected pyrazole core. In the next step, a

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• energy profile is seen for protonation-induced cyclization of 1, although the 6/6/6-tricyclic C3 tertiary cation is 7.1 kcal mol−1 higher in energy than its preceding intermediate (Figure 2C). A lower energy conformer of 1 exists, but we have been unable to find the corresponding cation A1b+, which