Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• interchanged. However, to our delight only the formation of the desired species 1a occurred, as evidenced by two-dimensional NMR measurements (for atom labeling scheme used for assignment of resonances see Figure S1 in Supporting Information File 1) and confirmed by SC-XRD (Figure 2), being in agreement with

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• of the scope of the reaction, substrates bearing an electron-rich functionality were less reactive than substrates with electron-deficient groups. Isotopic labeling revealed the oxygen functionality installed came from the peroxide initiator rather than the water present, suggesting the water plays

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• has set a milestone as a new and effective method for the synthesis of macromolecules [11]. Initiation of this reaction photocatalytically provides many advantages for the synthetic methodologies including bioconjugation, labeling, surface functionalization, dendrimer synthesis, polymer synthesis, and

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues for the development of RNA labeling tools based on tailored O6-alkylated preQ1 derivatives. Here, we report a robust synthesis for this class of pyrrolo[2,3-d

• solved by a hydration reaction sequence on a well-soluble dimethoxytritylated precursor via in situ oxime formation. The synthetic path now provides a solid foundation to access O6-alkylated 7-aminomethyl-7-deazaguanines for the development of RNA labeling tools based on the preQ1 class-I riboswitch

• (preQ1) [1]. Thus far, present-day riboswitches have only been known to bind – but not to be able to react – with their ligands [2][3]. This new finding now opens exciting avenues for the development of RNA labeling tools [4], in particular, for RNA methylation, and more generally, for RNA alkylation. To

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• , fluorinations, allylations, alkynylations, alkenylations, and fluorescent labeling with BODIPY. Moreover, manganese catalysis exhibits excellent functional group tolerance in late-stage C–H functionalization, indicating a robust and versatile catalytic system. Several challenges still remain since there are

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• -substituted β-diketones 2a and 2b (61 and 70% yield, respectively). Notably, the unsaturated carbocycles expected from palladium β-hydride elimination were not observed, indicating that an oxidant was not required in the reaction medium to regenerate the Pd(II) species. Later, deuterium-labeling experiments

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

• Greta Utecht-Jarzyńska,
• Karolina Nagła,
• Grzegorz Mlostoń,
• Heinz Heimgartner,
• Marcin Palusiak and
• Marcin Jasiński

Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

• of 3-trifluoromethylpyrazole derivative 9d. The labeling scheme of the asymmetric unit is shown. Anisotropic displacement parameters of nonhydrogen atoms are drawn as ellipsoids with a 50% probability level. N atoms in blue, O atoms in red, C atoms in grey, H atoms as small white spheres. Structure

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• irreversible one-electron oxidation at 0.80 V, in accordance with the involvement of oxygen in the reaction. Remarkably, when the glutarimide was labeled with deuterium in position 3, the deuterium labeling was transferred to the hydrocarbon liberated in the reaction, showing that hydrogen abstraction was

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• of 3-bromooxindoles with thiobenzamides. The Eschenmoser coupling reaction of 3-bromooxindole (1a) with thioacetamides. The synthesis of alternative 3-substituted oxindoles and their Eschenmoser coupling reaction with thiobenzamide (2a). A survey and labeling of synthesized 3-[amino(phenyl

Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• interaction. Isotopic labeling experiments demonstrated that also in laboratory cultures roseobacter group bacteria efficiently degrade DMSP into sulfur volatiles [22][23], but also from other sulfur sources including 2,3-dihydroxypropane-1-sulfonic acid (DHPS, Scheme 1C) labeling was efficiently incorporated

• identical to (E)-42. Feeding experiments with isotopically labeled precursors The biosynthesis of sulfur volatiles in C. marinus was investigated in a series of feeding experiments with isotopically labeled precursors. Feeding of (methyl-2H3)methionine resulted in the efficient incorporation of labeling

• incorporation of labeling into two or three of the sulfur atoms in 41 (Figure 3D; also here the signal at m/z = 213 represents inseparable unlabeled 41). In this experiment, the base peak did not change which allowed the localization of labeling specifically in the MeS group of 41. The fact that no

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• solvolysis reaction of 13f, a mixture of the major product 15f, resulting from solvent substitution, and the minor elimination product 16f was observed. Further, 14C labeling experiments on 13f confirmed that the formation of the ion pair 14fOTs was a reversible process [42]. Later, Liu et al. explored the

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• spiropentane to form methylenecyclobutane occurred with the cleavage of the C1–C2 bond [94]. Dolbier then used deuterium labeling to study the analogous reaction of 1,1-difluorospiropentane (101) (Scheme 47) [95]. The cleavage of the C1–C2 bond that is proximal to the fluorine resulted in the formation of two

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• . Accordingly, the field has developed to a stage that allows custom-design of RNA probes and tools for specific application. For example, investigations of RNA structures by NMR, EPR, or fluorescence spectroscopy require labeling of the RNA molecules with specific reporter groups [2][4][7][8][9][10]. Likewise

Encrypting messages with artificial bacterial receptors

• Pragati Kishore Prasad,
• Naama Lahav-Mankovski,
• Leila Motiei and
• David Margulies

Beilstein J. Org. Chem. 2020, 16, 2749–2756, doi:10.3762/bjoc.16.225

• encryption keys that change with time, we combined our expertise in modifying bacteria with synthetic receptors [2] and in message encryption using pattern-generating probes [5]. In our recent work, E. coli-expressing His-OmpC were decorated with fluorescently labeled synthetic receptors [2]. The labeling of

• colors, the individual bacteria were only labeled with a single dye (Figure 2). We hypothesized that incubating the bacteria with a mixture of three artificial receptors, each of which is appended with a distinct dye, should lead to a mixed labeling of each bacterium and to the generation of unique

• emission was recorded 24 hours after bacterial labeling. To encrypt the message, the encryption key is added to the numeric message, which affords the cipher text (Figure 5C). At this point, the message is secured and can be safely sent to a recipient who possesses identical synthetic receptors and

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• binding site. Here we discuss protein-based solution NMR techniques including classic 1H,15N-HSQC spectra, TROSY variants for large proteins, fast acquisition techniques and specific isotope labeling strategies, as well as the use of 13C-edited spectra and side chain specific spectra for lysine and

• protein. These methods require excess (5–20-fold) ligand together with relatively small protein concentrations (10–50 µM). Further advantages include no size limit for the protein, as well as no need for isotope labeling of the protein, assignment of protein resonances, and elaborate multidimensional NMR

• ligand-detected techniques. 1H,15N-HSQC and 1H,15N-TROSY-HSQC spectra 1H,15N-HSQC NMR spectra are a widely used tool to study the interaction of proteins with natural or synthetic ligands as well as other biomolecules [83]. This spectrum requires 15N-labeling of the protein of interest, which is easily

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• the mechanochemical approach (the B & B, ball milling for boronic acid conjugation) as bioconjugation strategy for the labeling of biocompatible carbohydrates. Fluorescent labeling is of key importance to follow up the fate of molecules and (nano)materials inside cells and in the human body. In this

• roughly equimolar amount of Dex and 1, in a glucose units/1 molar ratio of 60:1 (assuming an average molecular weight for Dex of 10 kDa). For the labeling in solution, Dex was dissolved in dry dimethyl sulfoxide (DMSO) and PBA-BODIPY (1) was added in roughly equimolar amounts (Scheme 1, route A). The

• and the two ethanol washings were kept separated for further analysis (vide infra). In order to evaluate the outcome of the two approaches in terms of dextran labeling with BODIPY, firstly, the amount of the recovered PBA-BODIPY (1, i.e., nonreacted 1) in each ethanol washing solution was quantified

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• complexed with streptavidin 24 (Figure 6). The resulting complex 25 was then incubated with HGM cells. These are stable cell lines, expressing the self-labeling HaloTag protein and GFP in the outer mitochondrial membrane (Figure 6a) [55]. If the complex 25 indeed reaches the cytosol, the chloroalkane will

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• for peptides can be powerful tools for labeling or inhibition. Finding those binding motifs, especially in water which competes for intermolecular H-bonds, poses an enormous challenge. A dynamic combinatorial library can be a powerful method to overcome this issue. We previously reported artificial

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• yields of 25–35% and with a radiochemical purity of more than 99%. The 18F-labeling of 4-borono-ᴅ,ʟ-phenylalanine (BPA) provided a potential tool for cancer treatment by boron neutron capture therapy [53] (Scheme 16). The syntheses of a variety of clinically relevant radiotracers including protected 4

Synthesis and properties of tetrathiafulvalenes bearing 6-aryl-1,4-dithiafulvenes

• Aya Yoshimura,
• Hitoshi Kimura,
• Kohei Kagawa,
• Mayuka Yoshioka,
• Toshiki Itou,
• Dhananjayan Vasu,
• Takashi Shirahata,
• Hideki Yorimitsu and
• Yohji Misaki

Beilstein J. Org. Chem. 2020, 16, 974–981, doi:10.3762/bjoc.16.86

• of the EBDT sites, b) the succeeding eight-electron oxidations of the non-equivalent EBDT sites, and c) the small ΔE value (0.16 V) of the EBDT sites. Target compounds. An optimized structure of 1a. a) Top view, b) side view, and c) labeling of the 1,3-dithiole rings. Molecular orbitals of 1a. Cyclic

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• corresponding aldehydes 36–42 were isolated with yields of 65−73%. Isotope labeling experiments Isotope labeling experiments were conducted to study the mechanism of the reductive carbonylation of aryl iodide with CO and H2 under our optimized conditions, using 13CO and D2 instead of CO and H2, respectively, as

• both CO and H2 participated in the formation of the formyl group in the product (Scheme 4a–c). Reaction mechanism and role of each component Based on the results from the labeling experiments a reaction mechanism for the reductive carbonylation of aryl iodides was proposed, as shown in Scheme 5 [57

• . Reaction conditions: PhI (1 mmol), RhCl3·3H2O (2.5 mol %), PPh3 (10 mol %), Et3N (1.2 mmol), DMA (2 mL), CO (5 bar), H2 (5 bar), 90 °C, 12 h. Isolated yields of the products are given and the structures were determined by NMR. Detailed information is given in Supporting Information File 1. Isotope-labeling

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• -dihydrothiazole (0.5 mmol), benzyl bromides (1.0 mmol), I2 (1.0 mmol) in DMC (2 mL), at 80 °C, under air for 16 h. aWith chloromethyl derivative. Transformation of 2-aminoethyl acetate derivative to 2-(dibenzylamino)ethanol. Control experiments and 18O-labeling experiment. Control experiments with radical

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• decade, numerous interdisciplinary studies have addressed the chemical mechanism of CotB2 catalysis utilizing different detection and analysis methods. Meguro and co-workers [41] established the chemical mechanism for the formation of cyclooctatin using isotope labeling experiments (Scheme 1). Recently

• isotope labeling experiments combined with QM calculations. Intermediate G forms via a 1,5-hydride shift from C6 to C10 to generate a homoallylic cation, and the formation of intermediate H occurs due to cyclization to yield a cyclopropyl ring. Intermediate I forms due to isomeric formation of a

• cyclopropylcarbinyl cation, as shown by isotope labeling [41]. QM calculations support this unusual 1,3-alkyl shift that interconverts H and I [38][39]. Finally, the cyclopropyl ring opens by virtue of a nucleophilic water attack, and cyclooctat-9-en-7-ol is formed. Although gas phase calculations shed light on the