Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• complex heterocycle products of general structure 9 and 11. Interestingly, Wu et al. demonstrated that the reaction did not proceed when paraformaldehyde is used as the C1 synthon, indicating that formaldehyde is not involved in the reaction [43]. Furthermore, in isotope labelling studies using DMSO-d6

• the alkene moiety of the amine. The resulting stabilized carbocation 15 is then captured by formaldehyde (generated in situ from DMSO) leading to an intermediate oxocarbenium 16 that undergoes a cyclization to obtain the sulfenylated oxazinane derivative 13. In isotope labelling experiments using DMSO

• to the resulting compounds. Once again, DMSO was confirmed as the origin of the methylene bridge by isotope labelling experiments using DMSO-d6. The proposed mechanism comprises the activation of DMSO by a Ru(III) catalyst and the role of Selectfluor working as the oxidant that allows the "activation

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• novel compound DPQ1. Keywords: deazapurines; heterocycles; pyrrolopyrimidines; queuosine; riboswitches; ribozymes; RNA alkylation; RNA labelling; Introduction Pre-queuosine 1 (preQ1) is a biosynthetic precursor of the hypermodified nucleoside queuosine (Q) that is found in the wobble position of

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• , deuterium labelling, rearrangements on stereodefined substrates, and structural analyses (NMR and X-ray) of the reaction products. RT-NMR-derived data strongly supported a pathway of alkene activation by the iodane, as opposed to the formation of an N-I(III) adduct. The presence of 5-exo-products, with

• support of a deuterium labelling experiment, also ruled out the possibility of an N-activation pathway. Therefore, the proposed mechanism involves BF3-coordinated I(III) iodane forming iodiranium(III) ions with the alkene, followed by diastereo-determining 5-exo-cyclisation. These transiently formed

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

• associated constants designed to reproduce the molecular geometry and selected properties of a system, as well as the naming and labelling of the system atoms, vary from one force field to another; therefore, it is important to ensure compatibility between the input file of the tested structure and the

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

• source in this reaction, a deuterium labelling experiment was conducted (Scheme 2C). Indeed, the deazaalloxazine derivative 6-d with quantitative incorporation of deuterium in C(5) position, was isolated and confirmed by 1H NMR analysis and mass spectrometry (for more details on possible reaction

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

• processes. The mechanism was initially postulated by Dreiding [30], and supported through isotope-labelling studies conducted by Abe and co-workers [31][32][33]. Subsequently, Cox et al. have elucidated the key enzyme SorbC responsible for the dearomatization process [34][35]. Scheme 4A illustrates the

• Diels–Alder (DA) reactions [45]. In the 1980s, the research group led by Nomura supported this biosynthetic hypothesis by isotope labelling experiments using cell cultures of Morus alba [46][47][48]. Furthermore, the proposed DA reaction precursors to 3, morachalcone A (44) and moracin C (47), were also

• substrate tolerance of MaDA for chemical probe design. After several attempts, Lei and co-workers designed and synthesized chemical probe 49 bearing a diazirine photoaffinity labelling unit with an alkyne tag on the phenolic hydroxy group of biosynthetic intermediate 44 (Scheme 5B). The treatment of

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• condensation with ketones, yielding an α,β-unsaturated compound, which was hydrogenated by the manganese hydride species, resulting in the final alkylated product (Scheme 25). A set of deuterium labelling tests and additional control studies determined that the alcohol dehydrogenation was aided by an

• substituted primary alcohols gave moderate to good yields (50–82%). Deuterium-labelling experiments with deuterated 1-phenylethanol-α-d1 and benzyl alcohol-α,α-d2 suggested a hydrogen auto-transfer and dehydrogenation process. The amido species Mn18-a generated from Mn18 by the base is responsible for the

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• the higher-substituted carbon atom to furnish intermediate species C. The irreversibility of the hydride addition and the regioselectivity thereof were supported by a deuterium labelling study with PhSiD3. The next steps involve homolytic cleavage of the cobalt–carbon bond to yield a carbon-centered

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• Zhiyong Yin Jeroen S. Dickschat Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany 10.3762/bjoc.20.67 Abstract An isotopic labelling method was developed to investigate substrate binding by ketosynthases, exemplified by the

• , to investigate the function of the KS domain BaeJ-KS2 the synthesis of 13C-labelled (S)-11 as a mimic of the intermediate bound to the ACP of module 3 was performed. It was planned to introduce the 13C-labelling from (5-13C)glutamate into the γ-aminobutyrate portion of (S)-11. For this purpose, the

• have established a new method based on stable isotope (13C) labelling to investigate the KS domain substrate specificity that makes use of simple 13C NMR analysis of protein preparations obtained by a buffer exchange after enzyme incubations with substrate surrogates (SNAC esters), and its application

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• unpleasant off-flavour [19][20]. The biosynthesis of 1 has been extensively studied. The initial hypothesis that 1 could be a degraded sesquiterpene [3] was not confirmed through isotopic labelling experiments that rather pointed to a methylated monoterpene [10][21]. Based on these experiments a biosynthetic

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• containing bioactive molecules (Scheme 10). To attain enantioselectivity a chiral phosphine oxide (43)-ligated Ni–Al bimetallic catalyst was used that was critical in improving the reactivity and controlling the selectivity of the reaction. Further, based on deuterium labelling experiments, KIE studies, and

• with various tethered alkenes, such as 1,1-disubstituted alkenes, styrene, diene, trisubstituted alkene and enamines. To get insights into the mechanism the authors conducted additional experiments including deuterium labelling reactions and proposed the mechanism depicted in Scheme 37b. Initially, the

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• synthesized a new chitosan bioconjugate CS-TPE with varying amounts of TPE labelling. It can self-assemble into fluorescent polymeric nanoparticles in an aqueous solution at pH 5.3, either alone or as a guest by electrostatic interaction with the TBTQ-C6 host. These nanoparticles were disassembled upon

• bioconjugates with different degrees of fluorescence labelling were synthesized as guests by controlling the feed ratios (Rf) of 4-(1,2,2-triphenylvinyl)benzaldehyde (TPE-CHO) [23] to 2 mol %, 10 mol %, and 20 mol %, respectively. They were obtained with chitosan and TPE-CHO through an aldimine condensation

• of these peaks confirmed that the TPE units were successfully labelled in the CS chain. The degree of fluorescence labelling (DL) of TPE attached to the CS chain was estimated by comparing the integrated areas of Har and H2 in the 1H NMR spectra (Figure 1) [24]. Accordingly, the DL at Rf = 2, 10 and

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• [58]. The alkyne 1 and dialkylborane reacted to give an alkenylborane 2. Transborylation with HBpin gave the alkenyl boronic ester 3 and regenerated the catalyst, HBR2. Isotopic labelling (H10Bpin) confirmed B–C(sp2)/B–H transborylation proceeded by σ-bond metathesis, and not ligand exchange. Using

• H-B-9-BBN, followed by B‒O/B‒H transborylation with HBpin to give the Bpin-enolate 52 and regenerate H-B-9-BBN (Scheme 12). Isotopic labelling with DBpin and H10Bpin supported this proposal. Fontaine reported that boric acid could be used as a precatalyst for the BH3-catalysed hydroboration of

• isotopic labelling and proposed to proceed by hydroboration of the allene 62 by the borane catalyst (H-B-9-BBN or 10-phenyl-9-borabicyclo[3.3.2]decane [Ph-BBD]) followed by rapid isomerisation from the (Z)-63 to (E)-allylborane 64 which underwent allylation of the ketone 65 to give an allylic borinic ester

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• spectrometry. Keywords: ApppI; ATP; deuterium labelling; HPCCC; mevalonate pathway; NMR; synthesis; Introduction It has become clear and evident that phosphonate chemistry plays a crucial role in drug research and development [1][2][3][4]. There are several phosphonate-containing compounds under research or

The enzyme mechanism of patchoulol synthase

• Houchao Xu,
• Bernd Goldfuss,
• Gregor Schnakenburg and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 13–24, doi:10.3762/bjoc.18.2

• Chemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany 10.3762/bjoc.18.2 Abstract Different mechanisms for the cyclisation of farnesyl pyrophosphate to patchoulol by the patchoulol synthase are discussed in the literature. They are based on isotopic labelling experiments, but the

• results from these experiments are contradictory. The present work reports on a reinvestigation of patchoulol biosynthesis by isotopic labelling experiments and computational chemistry. The results are in favour of a pathway through the neutral intermediates germacrene A and α-bulnesene that are both

• ), seychellene (11) and pogostol (12) as further side products [8]. The biosynthetic mechanism of the formation of compound 3 was investigated by several groups through isotopic labelling experiments. In 1987, Croteau et al. have suggested a pathway through 1,10-cyclisation of FPP to the (E,E)-germacradienyl

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• of biomolecules [35][36][37]. The approaches by Buchwald and Pentelute are suitable for selective, bioorthogonal labelling of cysteine- [38][39][40] and lysine-containing [41][42] peptides and proteins using stochiometric amounts of pre-formed Pd(II)-aryl complexes. They can further be applied for

• part in the destruction complex for β-catenin labelling in the canonical Wnt signalling. Loss-of-function mutations in this pathway lead to a dysregulated signal transduction causing cancer [75][76]. All-hydrocarbon stapled peptides comprising amino acids 467 to 481 of the axin CBD had been studied in

Synthesis of new bile acid-fused tetrazoles using the Schmidt reaction

• Dušan Đ. Škorić,
• Olivera R. Klisurić,
• Dimitar S. Jakimov,
• Marija N. Sakač and
• János J. Csanádi

Beilstein J. Org. Chem. 2021, 17, 2611–2620, doi:10.3762/bjoc.17.174

• molecular structures of compounds 13 and 14, with labelling of nonhydrogen atoms. Hydrogen atoms are drawn as spheres of arbitrary radii. Dose dependence of the cytotoxicity of tested compounds on treated cell lines. All compounds were tested in the concentration range 0.1–100 μM. A) Cytotoxicity of

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• of cross peaks in blue and in red refers to the hydrogens in Scheme 1 of same colour. Determination of the enantiomeric composition of 8 and 9 obtained from GGPP with SmTS1 enzyme variants through enantioselective labelling with (R)- and (S)-(1-13C,1-2H)GGPP. Compound 8 is obtained with different

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

• co-workers described the deuteration of several pharmaceuticals via an Fe-catalyzed C–H activation protocol (Scheme 29A and B) [161]. The site selectivity of the bulky iron catalyst was orthogonal to conventional iridium catalysts used in deuterium labelling experiments, allowing the

A new glance at the chemosphere of macroalgal–bacterial interactions: In situ profiling of metabolites in symbiosis by mass spectrometry

• Marine Vallet,
• Filip Kaftan,
• Veit Grabe,
• Fatemeh Ghaderiardakani,
• Simona Fenizia,
• Aleš Svatoš,
• Georg Pohnert and
• Thomas Wichard

Beilstein J. Org. Chem. 2021, 17, 1313–1322, doi:10.3762/bjoc.17.91

• combined LDI-MS imaging mass spectrometry and cLSM using a non-specific fluorescence labelling probe to visualise the bacterial cells living in symbiosis with U. mutabilis. Following a one-month incubation in clean cuvette slides placed in Petri dishes filled with medium, axenic and bacteria-inoculated U

Breakdown of 3-(allylsulfonio)propanoates in bacteria from the Roseobacter group yields garlic oil constituents

• Anuj Kumar Chhalodia and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 569–580, doi:10.3762/bjoc.17.51

• labelling into dimethyl disulfide (DMDS), the oxidative dimerization product from MeSH, showing the activity of the demethylation pathway in these bacteria. However, knockout of the dmdA gene in R. pomeroyi still gave a low incorporation of labelling into DMDS, suggesting the presence of another gene

• responsible for the demethylation activity [28]. Also the labelling from (34S)DMSP was efficiently incorporated into DMDS and dimethyl trisulfide (DMTS) [29]. Our previous investigations have also demonstrated that synthetic, i.e., non-natural DMSP analogues such as 3-(ethylmethyl)sulfoniopropanoate (EMSP), 3

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• labelling 19F NMR offers an attractive option for investigating the interactions between proteins and other biomolecules such as nucleic acids. Many of the advantages of 19F NMR have already been discussed but it is worth highlighting that it is a particularly useful technique to study large proteins that

• this technique is that the natural amino acid translation process incorporates the specific fluorinated analogue in all the locations where the original amino acid was present, resulting in a “global” labelling of the protein. This can result in a variety of unwanted side effects, including, in some

• -phase peptide synthesis (SPPS) methods (15 and 16, Figure 1). A second well-established methodology for the 19F isotopic labelling of protein and peptides involves the post-translational chemical conjugation of an 19F probe to specific amino acids present within the protein, typically cysteine and

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• Anwei Hou Jeroen S. Dickschat Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Strasse 1, 53127 Bonn, Germany 10.3762/bjoc.16.231 Abstract A 13C-labelling was introduced into each individual carbon of the recently discovered sestermobaraenes by the

• reaction proceeds in reverse order of a thermal reaction promoted by the thermal conditions of the gaschromatographic analysis) [14]. The fragmentation reactions of structurally simple compounds such as fatty acid methyl esters have been well investigated by isotopic labelling experiments [15][16] and the

• knowledge allows for structural predictions based on GC–MS data [17]. The deuterium labelling technique was also applied to other compound classes such as alkylbenzenes and ketones [18][19][20][21]. For terpenes, structural proposals can only be made based on the mass spectra for structurally less

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

• phenylboronic acid (PBA)-functionalized boron dipyrromethene (BODIPY) applying the ball milling approach. The ball milling formation of boron esters between PBA BODIPY and dextran proved to be more efficient in terms of reaction time, amount of reactants, and labelling degree compared to the corresponding

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• molecules were dyes used for the DNA/RNA labelling or even monitoring or influencing DNA/RNA function [3][4]. However, due to the complexity of DNA-coded or RNA-coded processes, also including epigenetics, there is permanent need for novel dyes, differing in selectivity, colour, or method of monitoring [5