Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• unambiguously established based on COSY, HSQC, and HMBC NMR-spectroscopic data. Further, the 15N NMR spectrum of 5a confirmed the typical pyrrole-like character of the N(12) atom as well as the pyridine-like character of the N(7) and N(14) atoms (Figure S31, Supporting Information File 1) [21][22]. The

• 15N NMR spectroscopy (NMR spectra of compounds 4a–h, 5a–c, 6a,b, and 10c are given in Figures S13–S43, Supporting Information File 1), mass spectrometry (Figures S44–S56, Supporting Information File 1), IR and UV–vis spectroscopy, as well as elemental analysis. The NMR spectra were recorded on the

• spectrometers Varian UNITY-300 (300 MHz for 1H) and Bruker AVANCE-600 (600 MHz for 1H, 151 MHz for 13C, and 60 MHz for 15N) in CDCl3 solutions. Chemical shifts are reported in ppm using the residual solvent peaks as reference (7.24 ppm for 1H, 77.0 ppm for 13C, and 384 ppm for 15N using nitromethane). Chemical

NMRium: Teaching nuclear magnetic resonance spectra interpretation in an online platform

• Luc Patiny,
• Hamed Musallam,
• Alejandro Bolaños,
• Michaël Zasso,
• Julien Wist,
• Metin Karayilan,
• Eva Ziegler,
• Johannes C. Liermann and
• Nils E. Schlörer

Beilstein J. Org. Chem. 2024, 20, 25–31, doi:10.3762/bjoc.20.4

• quiz material for intermediate to more advanced students. A third group of exercises includes additional experiments e.g., NOESY or 1D NOE spectra and 1D/2D heteronuclear experiments including nuclei such as 15N or 19F [43]. For all three exercise collections, students may draw a derived structure and

Chemistry of polyhalogenated nitrobutadienes, 17: Efficient synthesis of persubstituted chloroquinolinyl-1H-pyrazoles and evaluation of their antimalarial, anti-SARS-CoV-2, antibacterial, and cytotoxic activities

• Viktor A. Zapol’skii,
• Isabell Berneburg,
• Ursula Bilitewski,
• Melissa Dillenberger,
• Katja Becker,
• Stefan Jungwirth,
• Aditya Shekhar,
• Bastian Krueger and
• Dieter E. Kaufmann

Beilstein J. Org. Chem. 2022, 18, 524–532, doi:10.3762/bjoc.18.54

• (1H, 13C, 14N, 15N NMR, IR, MS and HRMS), copies of spectra, and detailed procedures of biological assays. Acknowledgements We thank Dr. G. Dräger (Leibniz University of Hannover, Germany) for HRMS measurements, Siegrid Franke (Biochemistry and Molecular Biology Interdisciplinary Research Center

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• analysis, 1H, 13C, and 15N NMR spectroscopy, HRMS, and single-crystal X-ray diffraction data. Keywords: β-enamino ketoesters; heterocyclic amino acids; 15N-labeled 1,2-oxazole; NMR (1H; 13C; 15N); 1,2-oxazole (isoxazole); X-ray structure analysis; Introduction 1,2-Oxazoles (isoxazoles) constitute an

• -HMBC spectra. The aforementioned enamine proton and protons 2’(4’)-H (δ 4.00-4.09 ppm) from the azetidine ring system shared the HMBC cross-peak with the ketone carbonyl carbon (δ 195.4 ppm). Finally, in the 1H,15N-HMBC spectrum of 3a, an expected long-range correlation between the enamine proton (δ

• -ADEQUATE spectrum thus allowing to assign a neighboring quaternary carbons C-4 (δ 109.9 ppm) and C-5 (δ 175.4 ppm), H–C(3)–C(4) and H–C(3’)–C(5), respectively. The 1H,15N-HMBC experiment revealed an expected long-range correlation between the 1,2-oxazole methine H-3 proton (δ 8.50 ppm) and nitrogen N-2

Silica gel and microwave-promoted synthesis of dihydropyrrolizines and tetrahydroindolizines from enaminones

• Robin Klintworth,
• Garreth L. Morgans,
• Stefania M. Scalzullo,
• Charles B. de Koning,
• Willem A. L. van Otterlo and
• Joseph P. Michael

Beilstein J. Org. Chem. 2021, 17, 2543–2552, doi:10.3762/bjoc.17.170

• yields and decomposition was still evident. 2-Bromophenylenaminone 15m gave a disappointing yield of 46% for 19m after a comparatively long reaction time of nine minutes, while the more electron-rich 2-bromo-4,5-dimethoxy analogue 15n gave an even lower yield of 35% in the same reaction time. However

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

• -diaminopyrimidin-4-one to the nitroolefin 2-[(2E)-3-nitroprop-2-en-1-yl]-1H-isoindole-1,3(2H)-dione [23]. Finally, Carell reported a cycloaddition route relying on α-brominated 3-phthalimidopropanal and diaminopyrimidin-4-one [24][25]. We further optimized this path for the synthesis of 15N-labeled prequeuosine

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

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

• in the analysis of the dissociation constants due to the higher spectrum resolution and greater chemical environment sensitivity of the 19F nuclei when compared to that offered by the 15N. Due to the fact that different regions of a protein give rise to unique NMR resonances, protein-observed

• . By comparing the results obtained using both, the newly proposed 19F NMR-based analysis and the traditional 2D 15N,1H-HSQC experiments they could demonstrate that simple 19F NMR line shape analysis achieved comparable high quantitative accuracy in the determination of all binding parameters. In

• , providing simultaneous access to both structural and dynamic information that would be difficult to obtain using traditional 13C, 1H and 15N,1H-HSQC NMR techniques. Protein folding From the late 1960s and early 1970s 19F NMR has firmly established itself as a highly versatile and powerful analytical tool

Au(III) complexes with tetradentate-cyclam-based ligands

• Ann Christin Reiersølmoen,
• Thomas N. Solvi and
• Anne Fiksdahl

Beilstein J. Org. Chem. 2021, 17, 186–192, doi:10.3762/bjoc.17.18

• moderate to excellent yields of tetracoordinated 5a-Au(III) and 6a-Au(III) N,N,N,N-complexes with alternating five- and six-membered chelate rings (50% and 96%, respectively, Scheme 3). Monitoring the formation of complex 5a-Au(III), using 1H NMR, and 1H,15N-HMBC, clearly indicated a tetra-nitrogen

• ) coordination [43][45][46], Likewise, Δδ1Hcoord 0.3–0.5 ppm for all the neighboring N–CH and N–CH2 protons indicated ligand tetra-coordination to Au(III), as well. Upon coordination of ligand 5a, four different 15N NMR values for the nitrogens were observed. This might be explained by the nitrogens becoming non

• cyclam tetraamino-coordination was obtained by 1H,15N-HMBC NMR. The polyamides (1, 2) failed to undergo Au(III) coordination, which confirmed the previously observed resistance of amides to coordinate to Au(III). The catalytic ability of the new Au(III) complexes were screened in selected test reactions

Synthesis of purines and adenines containing the hexafluoroisopropyl group

• Viacheslav Petrov,
• Rebecca J. Dooley,
• Alexander A. Marchione,
• Elizabeth L. Diaz,
• Brittany S. Clem and
• William Marshall

Beilstein J. Org. Chem. 2020, 16, 2739–2748, doi:10.3762/bjoc.16.224

• spectroscopy, was at least 99%, unless stated otherwise. Standard NMR experiments The NMR data presented in Table 2 and Table 3 were derived from spectra acquired on a Bruker Neo spectrometer with a 9.4 T magnetic field, equipped with a 5 mm 15N,77Se, 31P {19F,1H} nitrogen cryoprobe. Chemical shifts are

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

• 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

• achieved by expression in minimal media in the presence of 15N ammonium salts. A 1H,15N-HSQC spectrum shows all N–H correlations that are moderately stable and do not exchange with the solvent water too quickly, which includes the amide NHs and some side chain NHs, e.g., the side chain amides of asparagine

Regio- and stereoselective synthesis of new ensembles of diversely functionalized 1,3-thiaselenol-2-ylmethyl selenides by a double rearrangement reaction

• Svetlana V. Amosova,
• Andrey A. Filippov,
• Nataliya A. Makhaeva,
• Alexander I. Albanov and
• Vladimir A. Potapov

Beilstein J. Org. Chem. 2020, 16, 515–523, doi:10.3762/bjoc.16.47

• and 8 were proved by 1H, 13C, 15N, 19F and 77Se NMR and mass spectrometry. The composition of the products was confirmed by elemental analysis. Molecular ions of the synthesized compounds were observed in their mass spectra. Two doublets of the olefinic protons of the SCH=CHSe group with 3J = 6.3–6.6

• Information Supporting Information File 234: Experimental section and 1H, 13C, 15N, 19F and 77Se NMR spectra of all synthesized compounds. Acknowledgements The authors thank Baikal Analytical Center SB RAS for providing the instrumental equipment for structural investigations.

Sugar-derived oxazolone pseudotetrapeptide as γ-turn inducer and anion-selective transporter

• Sachin S. Burade,
• Sushil V. Pawar,
• Tanmoy Saha,
• Navanath Kumbhar,
• Amol S. Kotmale,
• Manzoor Ahmad,
• Pinaki Talukdar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2019, 15, 2419–2427, doi:10.3762/bjoc.15.234

• of 2a, the assignment of chemical shifts to different protons was made based on 1H,1H-COSY, 1H,13C-HMBC/HSQC, NOESY, and 1H,15N-HSQC/HMBC studies (Figures S5–S10 in Supporting Information File 1) and values thus obtained are given in Table S1 in Supporting Information File 1. The IR spectrum of 2a

• signal at δ 163.0 ppm was assigned to the -C=N functionality. The 1H,15N-HSQC and 1H,15N-HMBC spectra showed a signal at δ 246.0 ppm that was assigned to the imine (C=N-) nitrogen. The signal at δ 26.2 ppm was assigned to the amine (NH2) nitrogen. The signals at δ 112.8 and δ 114.1 ppm were due to the

• nitrogen of amide (CONH) groups. Based on the 15N NMR spectra, the presence of the oxazolone ring at the C-terminus in 2a was confirmed [21][22][23]. The 1H NMR spectra of N-acylated compound 2b showed three downfield signals at δ 8.24, 8.19 and 8.09 ppm due to the three amide NHs. An additional singlet at

Reactions of 2-carbonyl- and 2-hydroxy(or methoxy)alkyl-substituted benzimidazoles with arenes in the superacid CF₃SO₃H. NMR and DFT studies of dicationic electrophilic species

• Dmitry S. Ryabukhin,
• Alexey N. Turdakov,
• Natalia S. Soldatova,
• Mikhail O. Kompanets,
• Alexander Yu. Ivanov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1962–1973, doi:10.3762/bjoc.15.191

• benzimidazole system. The same applies to the reactivity of the carbon C2 in dications I and II. Then we studied the protonation of benzimidazoles in the superacid TfOH by means of NMR. Selected 1H, 13C and 15N NMR data for starting neutral benzimidazoles 1, 3a, and 7 (in CDCl3, (CD3)2CO, CD3OD) and their

• 56.9 ppm, which are close to the shifts in starting neutral precursors 3a and 7, proves unambiguously that no dehydration of these species leading to heteroaromatic benzyl-type cations take place. Based on HSQC and HMBC N–H correlations, we were able to measure 15N chemical shifts of nitrogen atoms for

• –11. Reaction mechanism of the formation of compounds 12. Selected calculated [DFT, 6-311+G(2d,2p) basis set] electronic characteristics of the protonated forms of benzimidazoles. 1H, 13C and 15N NMR data of benzimidazoles 1, 3a, 7 in the corresponding deuterated solvent and species I', III', VIII' in

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• -catalyzed coupling of 4-iodo-1-phenyl-1H-pyrazol-3-ol with ethyne derivatives. The structures of the obtained target compounds were unequivocally confirmed by detailed 1H, 13C and 15N NMR spectroscopic experiments, HRMS and a single-crystal X-ray diffraction analyses. This silver(I)-mediated 5-endo-dig

• of the 2H-furo[2,3-c]pyrazole ring system in the regions of δ 115.0–116.3 for C-3, δ 113.1–113.9 for C-3a, δ 94.5–96.8 for C-4, δ 156.1–163.8 for C-5 and δ 168.4–169.0 ppm for C-6a. The 15N spectra of 4b–e exhibited signals for two nitrogen atoms in the regions of δ −169.4 to −172.6 for N-2 and δ

Design of indole- and MCR-based macrocycles as p53-MDM2 antagonists

• Constantinos G. Neochoritis,
• Maryam Kazemi Miraki,
• Eman M. M. Abdelraheem,
• Ewa Surmiak,
• Tryfon Zarganes-Tzitzikas,
• Beata Łabuzek,
• Tad A. Holak and
• Alexander Dömling

Beilstein J. Org. Chem. 2019, 15, 513–520, doi:10.3762/bjoc.15.45

• for p53-MDM2 inhibition by fluorescence polarization and 1H,15N HSQC NMR measurements confirm MDM2 binding. Keywords: 1H,15N HSQC NMR; indole; macrocycles; multicomponent; p53-MDM2; Ugi reaction; Introduction Macrocycles are the chemical entities that are consisting of a 12-membered or even bigger

• (Scheme 3). In order to exclude false positive hits, two biorthogonal assays were chosen; 1H,15N HSQC NMR and fluorescence polarization (FP, Table 1). FP assay was employed to determine the inhibitory affinities (Ki) of the derivatives against MDM2 as previously described [36]. Besides 2h (Ki = 2.3 μΜ, Kd

• = 12.1 μΜ), it was shown that 2i demonstrated a promising activity with a Ki of 5.5 μΜ. Furthermore, 1H,15N HSQC showed a Kd of 4.8 μΜ (Table 1, Figure 2). Moreover, macrocycles 2g and 2n demonstrated a Kd of 9 μΜ and 17 μΜ, respectively (Table 1). With this preliminary analysis, it was found that a ring

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• for the APH+ form. However, solid-state NMR using 15N and 13C-labeled ThDP has been used to identify APH+ on pyruvate decarboxylase and the E1 component of the pyruvate dehydrogenase complex [18]. In addition to the plethora of experimental investigations, a number of computational studies have

Thermophilic phosphoribosyltransferases Thermus thermophilus HB27 in nucleotide synthesis

• Ilja V. Fateev,
• Ekaterina V. Sinitsina,
• Aiguzel U. Bikanasova,
• Maria A. Kostromina,
• Elena S. Tuzova,
• Larisa V. Esipova,
• Tatiana I. Muravyova,
• Alexei L. Kayushin,
• Irina D. Konstantinova and
• Roman S. Esipov

Beilstein J. Org. Chem. 2018, 14, 3098–3105, doi:10.3762/bjoc.14.289

• ’,2’ = 6 Hz, 1Н, H1’), 4.61 (m, 1Н, H2’), 4.23 (m, 1Н, H3’), 4.06 (m, 1Н, H4’), 3.84 (m, 2Н, H5a’, H5b’) ppm; 13C NMR (DMSО-d6) δ 156.61 (C2 or C6), 153.01 (C6 or C2), 150.73 (C4), 139.68 (C8), 117.57 (C5), 86.40 (C1’), 84.52 (C4’), 74.13 (C2’), 71.06 (C3’), 3.94 (C5’) ppm; 15N NMR (DMSО-d6) δ 242.7

• (C4a), 88.16 (C1’), 83.27 (C4’), 73.39 (C2’), 71.38 (C3’), 64.76 (C5’) ppm; 15N NMR (DMSО-d6) δ 302.8 (N2), 210.6 (N7), 204.9 (N1), 171.1 (N5). Abbreviations APRT – adenine phosphoribosyltransferase; HPRT – hypoxathine phosphoribosyltransferase; PRPPS – phosphoribosylpyrophosphate synthetase; RK

Protein–protein interactions in bacteria: a promising and challenging avenue towards the discovery of new antibiotics

• Laura Carro

Beilstein J. Org. Chem. 2018, 14, 2881–2896, doi:10.3762/bjoc.14.267

• -transfer difference NMR (STD-NMR) led to the identification of thirty fragments. Subsequent 2D-15N–1H HSQC NMR returned four fragment hits 28–31 (Figure 7), with binding affinities, determined by NMR titration, in the low millimolar range. Of all of the fragments, tetrazole 31 was chosen for further

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• and 8.75 ppm (J = 9.5 and 9.3 Hz) were identified as the NH and NH* signals of 1 and 2 from their correlation in the 15N,1H-HSQC NMR spectrum, respectively. They showed couplings to H-26 (4.96 ppm) and H-26* (4.91 ppm). The latter showed further 1H couplings to doublets of OH and OH* signals at 5.89

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

• Gernot A. Eller,
• Gytė Vilkauskaitė,
• Algirdas Šačkus,
• Vytas Martynaitis,
• Ashenafi Damtew Mamuye,
• Vittorio Pace and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2018, 14, 1287–1292, doi:10.3762/bjoc.14.110

• of 5-hydroxypyrazole-4-carboxylates in refluxing thionyl chloride. The obtained diesters can be transformed into the corresponding 4,4'-bipyrazoles via alkaline hydrolysis and subsequent decarboxylation. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products

• prepared. Moreover, the structure of a representative 5,5'-dioxo-4,4'-bipyrazole-4,4'-dicarboxylate was confirmed by X-ray crystal structure analysis. Keywords: dimerization; NMR (1H; 13C; 15N); pyrazolones; thionyl chloride; X-ray structure analysis; Introduction Many biologically active substances

• of all compounds treated within this study are indicated. Full and unambiguous assignment of 1H, 13C and nearly all 15N NMR resonances was achieved by combining standard NMR techniques [33], such as fully 1H-coupled 13C NMR spectra, APT, gs-HSQC, gs-HMBC, gs-HSQC-TOCSY, COSY, TOCSY and NOESY

Phosphodiester models for cleavage of nucleic acids

• Satu Mikkola,
• Tuomas Lönnberg and
• Harri Lönnberg

Beilstein J. Org. Chem. 2018, 14, 803–837, doi:10.3762/bjoc.14.68

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• products in small amounts namely 3(5)-methyl-5(3)-phenyl-1H-pyrazole (121) obtained by CN bond cleavage and benzoic acid (122) was also observed (Scheme 33). The structure of the regioisomer was established unequivocally by performing 1H,13C-HMQC, 1H,13C- and 1H,15N-HMBC experiments. Aqueous mediated

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• -1H and 1H-13C NMR correlation experiments (COSY and HMBC, respectively) or nuclear Overhauser effect spectroscopy (NOESY or ROESY). The selective incorporation of 15N-labelled atoms in different positions of the heterocyclic core allowed for the use of 1H-15N (JHN) and 13C-15N (JCN) coupling

• of azolo-azines and 1-adamatanol in TFA solution. For azolo-1,2,4-triazinones, the formation of mixtures of N-adamantyl derivatives was observed. The JHN and JCN values were measured using amplitude-modulated 1D 1H spin-echo experiments with the selective inversion of the 15N nuclei and line-shape

• analysis in the 1D 13С spectra acquired with selective 15N decoupling, respectively. Additional spin–spin interactions were detected in the 15N-HMBC spectra. NMR data and DFT (density functional theory) calculations permitted to suggest a possible mechanism of isomerization for the adamantylated products