Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• nuclear Overhauser effect (NOE) NMR spectroscopy are useful tools to monitor and control the chirality when utilizing a modified 1,3-oxathiolane intermediate 65 obtained via enzyme-catalyzed selective hydrolysis. Hu et al. [61] established a green catalyst, STS, for the asymmetric synthesis of lamivudine

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

• observations about the preferred migration of the more substituted carbon atom during the Schmidt reaction [49]. Also, a retention of configuration at the C-13 position was confirmed by NOE NMR experiments. The chemical shift of some protons in compounds 13 and 14 exhibited effects of magnetic anisotropy from

Cascade intramolecular Prins/Friedel–Crafts cyclization for the synthesis of 4-aryltetralin-2-ols and 5-aryltetrahydro-5H-benzo[7]annulen-7-ols

• Jie Zheng,
• Shuyu Meng and
• Quanrui Wang

Beilstein J. Org. Chem. 2021, 17, 1481–1489, doi:10.3762/bjoc.17.104

• 13C NMR chemical shift for C2 is expected to be in the range of 60 to 70 ppm and the assignment of H3 was based on the HSQC correlation between H3 and C2. Then, H1 and H2 could be assigned by COSY and HSQC experiments. Following that, NOE analysis was applied to analyze the relative cis- and trans

• -configuration. If there is an NOE correlation between H1 and H3, and meanwhile H1 and H3 also have a strong NOE correlation with H2a, the compound is assigned to be cis-configured. Otherwise, it was assigned to be the trans-isomer (see Supporting Information File 1 for details). Having determined the suitable

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• and methods to prepare the pellet feed containing VLP-dsRNAvp28. Acknowledgements We thank Francisco Ruiz-Medina, for TEM analysis, Dr. Noe Ruiz-Garcia for helping with the qPCR statistical analysis, Dr. Mario Galaviz from UABC, and Mochis Zazueta Urias from SRY Promotora Acuícola S.A. de C.V

Synthesis of 10-O-aryl-substituted berberine derivatives by Chan–Evans–Lam coupling and investigation of their DNA-binding properties

• Peter Jonas Wickhorst,
• Mathilda Blachnik,
• Denisa Lagumdzija and
• Heiko Ihmels

Beilstein J. Org. Chem. 2021, 17, 991–1000, doi:10.3762/bjoc.17.81

• reaction was exemplarily studied by NOESY NMR experiments. Based on these results, the formation of the 10-O-arylated regioisomer 4b was unambiguously confirmed by a clear NOE crosspeak between the protons 2’-H and 6’-H of the O-aryl group and the 11-H proton of the berberine (Figure S12, Supporting

• Information File 1), whereas an NOE between the O-aryl group and the 8-H proton, as expected for the 9-O-arylated product, was not observed. Furthermore, mass spectrometric data and elemental analysis data were consistent with the structure assignment of product 4b. To assess whether the formation of the

Stereoselective synthesis and transformation of pinane-based 2-amino-1,3-diols

• Ákos Bajtel,
• Mounir Raji,
• Matti Haukka,
• Ferenc Fülöp and
• Zsolt Szakonyi

Beilstein J. Org. Chem. 2021, 17, 983–990, doi:10.3762/bjoc.17.80

• 9 ring system (Scheme 1). The absolute configuration of compound 9 was determined by 2D NMR spectroscopic techniques. Clear NOE signals were observed between the H-7a and Me-10 as well as the Ha-9 and Me-10 protons. Beside NOESY experiments, the structure was also elucidated by X-ray crystallography

• exclusively [41]. The configuration of oxazolidine 17 was determined by 2D NMR spectroscopic techniques. Clear NOE signals were observed between the H-7a and Me-10 as well as the Ha-9 and Me-10 protons. In addition to NOESY experiments, the structure was also elucidated by X-ray crystallography (Figure 3

Stereoselective syntheses of 3-aminocyclooctanetriols and halocyclooctanetriols

• Emine Salamci and
• Yunus Zozik

Beilstein J. Org. Chem. 2021, 17, 705–710, doi:10.3762/bjoc.17.59

• protons H-2 and H-4 in the COSY spectrum. Moreover, the fact that the proton H-3 gives positive NOE clearly indicates that the proton H-3 should have a cis configuration relative to the proton H-1. On the other hand, the fact that the proton H-1 gives a positive NOE’s clearly indicates that the proton H-1

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• were accompanied by traces of a C3–C4 cis-diastereomer (not shown). The relative configuration of pyrrolidone 12l was assigned by NOE experiments of 3-(2-oxocyclohexyl)lactams 13l prepared from 12l by Dess–Martin oxidation (vide infra). The thermal cyclization of compounds 9m,n with N

• also occurred exclusively at the convex face of the bicyclic system. The configurations of the fused lactams were assigned by chemical derivatization and NOE experiments (vide infra). Functionalization reactions of lactams 12 Base-mediated isomerization reactions Lactams 12 are mixtures of two, four

• orientation of the substituents at C3 and C4 of the pyrrolidone ring of 13b was confirmed by NOE experiments (see Supporting Information File 1 for details). The trans/cis mixture of 12f was similarly oxidized providing the pyrrolidone diastereomers 13f in good yield and unchanged ratio (Table 5, entry 5

Unexpected rearrangements and a novel synthesis of 1,1-dichloro-1-alkenones from 1,1,1-trifluoroalkanones with aluminium trichloride

• Beatrice Lansbergen,
• Catherine S. Meister and
• Michael C. McLeod

Beilstein J. Org. Chem. 2021, 17, 404–409, doi:10.3762/bjoc.17.36

• , with an HMBC cross-peak between the aryl ring and the alkene moiety proving most illuminating (see Supporting Information File 1). The geometry of the double bond was determined from a NOE interaction between the alkene proton and the ring hydrogen atoms. This molecule could not however be detected by

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• stereochemical assignments were additionally confirmed by nuclear Overhauser effect spectroscopy (NOE). The peak of H6 was selected to be selectively excited for each isomer. As expected, in the case of endo-2l the NOE peaks resulted from the interaction of exo-H6 with H1 and H7a were observed. Whereas for exo

• assignment of norbornenes 2 by 1H (a) and NOE (b) NMR spectroscopy. 13C NMR spectrum of the mixture of exo- and endo-isomers of norbornene 2l. The predicted reaction pathway for the Diels–Alder reaction of nitrostyrene 1h with CPD is displayed. The path leading to the endo-2h isomer has a lower lying

Direct synthesis of anomeric tetrazolyl iminosugars from sugar-derived lactams

• Michał M. Więcław and
• Bartłomiej Furman

Beilstein J. Org. Chem. 2021, 17, 115–123, doi:10.3762/bjoc.17.12

• determine the structure of compounds 3a and 3e unambiguously by means of X-ray analysis, as shown in Figure 2. The configuration of the remaining glucose based products 3 was easily determined by the analysis of 1H-1H coupling constants and NOE effects. Unfortunately, the same approach was not possible in

• . But alas, this value is unknown, due to overlapping and broadening of the relevant signals in the 1H NMR spectrum of the compound in question. For the same reasons NOE effects present in 2-epi-5a cannot be accurately interpreted. However, analysis of the NOE effects in 5a, particularly a small effect

• couplings and NOE effects shown. Our previous efforts in the field of functionalization of sugar-derived lactams. Preliminary experiment in search of a procedure for the synthesis of 2-(1H-tetrazol-5-yl)-iminosugars. Synthesis of a new class of alkaloid scaffold using the presented methodology. Synthesis of a

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

• effect (NOE), e.g., saturation transfer difference (STD, reviewed in [89]), WaterLOGSY (recently reviewed in [90]) and transfer-NOE (trNOE, recently reviewed in [91]) experiments. The second set of methods is based on measuring the change of relaxation times (T1/T2/T1ρ) upon binding of a ligand to a

• the ligand needs to dissociate again from the protein in order to be detected. Therefore, strong (nM or better) binders are not suitable for these experiments. No information about the binding site(s) on the protein is obtained. Magnetization transfer via NOE depends on a molecule’s correlation

• function and thus on its size. Small molecules <1000 g/mol show positive NOEs while large molecules like proteins exhibit negative NOEs. Around a molecular weight of ≈1000–1500 g/mol, the NOE passes through zero, meaning no NOE signal can be measured, even if molecules are in close enough proximity. A lot

Chan–Evans–Lam N1-(het)arylation and N1-alkеnylation of 4-fluoroalkylpyrimidin-2(1H)-ones

• Viktor M. Tkachuk,
• Oleh O. Lukianov,
• Mykhailo V. Vovk,
• Isabelle Gillaizeau and
• Volodymyr A. Sukach

Beilstein J. Org. Chem. 2020, 16, 2304–2313, doi:10.3762/bjoc.16.191

• %, respectively. In contrast, the fluorine ortho-substituent drastically inhibited the reaction, which is evidently attributed more to electronic than to steric effects. The formation of alternative O-arylated products was ruled out by conducting a NOE NMR experiment with compound 3b as an example. Saturation of

• ) as a reagent; the thus obtained N1-styryl-substituted 4-trifluoromethylpyrimidin-2(1H)-one 5a obviously has considerable synthetic potential [49][50]. The stereochemistry of compound 5a was confirmed by a NOE NMR experiment, which demonstrated significant spatial interaction between the H6 and Hb

• 13C NMR spectra. Acknowledgements The authors are very grateful to Dr. V. Polovinko for NOE experiments and A. Skreminskij for HRMS analytical data.

Reactions of 3-aryl-1-(trifluoromethyl)prop-2-yn-1-iminium salts with 1,3-dienes and styrenes

• Thomas Schneider,
• Michael Keim,
• Bianca Seitz and
• Gerhard Maas

Beilstein J. Org. Chem. 2020, 16, 2064–2072, doi:10.3762/bjoc.16.173

• with 1,2-dihydronaphthalene, a cyclic styrene derivative (Scheme 6; compare also the cyclobutene byproduct in Scheme 2). The structure of 18 was derived from its 1H and 13C NMR chemical shifts; a NOE NMR experiment indicated the vicinity of the phenyl ring and the CH2CH part or the molecule in line

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• it was observed that the predominant product in each case was Z-30 and Z-31, respectively, which presumably result from γ-addition of the nucleophile. This was confirmed by 1H NMR NOE analysis of Z-30, where an enhancement between the enamide proton and the methylene proton were observed, as shown in

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• , indicating the presence of strong hydrogen bonds also in solution. These data suggest that the structures of the predominating conformers should be similar in the solid and liquid phases. Furthermore, we have managed to detect NOE steric proximities between the aldehyde H atom and the H-C(7) (in compounds 3b

• pellets. 1H NMR, 13C NMR, DeptQ, Dept-135, edHSQC, selective HSQC, HMBC, selective HMBC, NOESY, 1H,1H-COSY, one-dimensional selective NOE, and selective TOCSY spectra were recorded at 295 K on a Bruker Avance III HD 600 (Billerica, MA, USA; 600 and 150 MHz for 1H and 13C NMR spectra, respectively

• -dimensional sel-NOE experiments on signals 9.78, 6.88, 6.30, 5.91, 4.59, and 3.42 elucidated the characteristic steric proximities (pages S21 and S22 in Supporting Information File 1) and proved the SR–RS-type structure. The 13C signal assignment was supported with HSQC and HMBC spectra (pages S23 and S24 in

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• of 13a-C, 13-C and 15-C (signals highlighted in green, Figure 3). It is noteworthy that in the reduction process of the DHBER 2 precursors, a single diastereoisomer of the corresponding THBERs 3 is produced according to 1H and 13C NMR data. In particular, the NOE correlation between C13−H and C13a−H

• . 1H,1H-COSY spectrum of DHBER 2a [65]. Detail of the hydrazone signal in the HMBC spectrum of THBER 3a. Comparison between 1H NMR spectra of DHBER 2a and of THBER 3a. NOE correlation between C13−H and C13a−H of THBER 3a. Effects of 25 µM hydrazono-DHBERs 2a–n (A) and hydrazono-THBERs 3a–g,i–n [70] (B

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• Table 1. The relative configuration was determined from proton coupling constants and NOE data (Table 1, Figure 4). NOESY cross peaks between H-3 (δ 0.55 m), and H-22a (δ 0.43 dd, J = 3.9, 9.2 Hz), H3-21 (δ 0.94 s), and H3-23 (δ 0.95 s), as well as between H3-23 and H-24a (δ 4.91 d, J = 12.9 Hz), H-24b

• 12-deacetoxy-4-demethyl-11,24-diacetoxy-3,4-methylenedeoxoscalarin in all three samples. Proposed relative configuration of 12-deacetoxy-4-demethyl-11,24-diacetoxy-3,4-methylenedeoxoscalarin. Selected NOE correlations are indicated with arrows. The model was obtained using Avogadro, an open-source

One-step route to tricyclic fused 1,2,3,4-tetrahydroisoquinoline systems via the Castagnoli–Cushman protocol

• Aleksandar Pashev,
• Nikola Burdzhiev and
• Elena Stanoeva

Beilstein J. Org. Chem. 2020, 16, 1456–1464, doi:10.3762/bjoc.16.121

• chromatography to give the individual diastereomers. The acid (−)-trans-22 and its methyl ester are known compounds, which were prepared by an independent method [35]. NOESY experiments were used to examine the stereochemical assignments in compounds 21–24. The cis diastereomers 22–24 showed distinct NOE cross

• -signals between protons H-1 and H-11b, and for cis-21 – between H-1 and H-10b. No such NOE peaks were identified in the spectra of the trans isomers (Figure 2). Further, the assignment of the relative configuration of the products 22–24 was supported by the vicinal coupling constants 3J1,11b for H-1 and H

• recrystallization. Compounds comprising a benzo[a]quinolizidine ring system. Representative NOE interactions in cis and trans-21–24 (only one enantiomer is shown). X-ray crystal structure of products 25 and 26. Representative NOE interactions in 28 and 29. Reactions between enolizable anhydrides and imines

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• irradiation of the H-4 proton resulted in a stronger enhancement of the signal corresponding to the pseudoequatorial proton H-5b (1.5%), whereas a weak NOE was observed for H-3 (0.4%) and the pseudoaxial H-5a proton (0.5%). Furthermore, the protons of the phenyl ring at C-3 were also affected (0.8%). The

• (Figure 3). Not surprisingly, the NOE between the protons H-3 and H-4 was significantly stronger (2.4%) than in the respective trans isomer 8a. The C-3/4-cis isoxazolidin-4-ols 10b and 10c were obtained from the ketones 9b and 9c in a similar manner in satisfying (51%) and good yield (72%), respectively

• NOE enhancements observed in the isoxazolidin-4-ol trans-8a. The arrows show the NOESY correlations. Selected NOE enhancements observed in the isoxazolidin-4-ol cis-10a. The arrows show the NOESY correlations. Synthetic approach towards isoxazolidin-4-ols via the regioselective reductive cleavage of

Preparation of 2-phospholene oxides by the isomerization of 3-phospholene oxides

• Péter Bagi,
• Réka Herbay,
• Nikolett Péczka,
• Zoltán Mucsi,
• István Timári and
• György Keglevich

Beilstein J. Org. Chem. 2020, 16, 818–832, doi:10.3762/bjoc.16.75

• -diastereomers (cis- and trans-10) were separated by column chromatography, and they were identified by nuclear Overhauser effect (NOE) NMR spectroscopy. In the ROESY spectrum of the cis-diastereomer (cis-10), the phenyl 1H resonances give NOE/ROE crosspeaks with the C(4)H and one of the C(5)H2 1H resonances. By

• contrast, in the spectrum of trans-diastereomer (trans-10), phenyl 1H resonances give NOE/ROE crosspeaks with C(4)-methyl and the other one of the C(5)H2 1H signals (see Supporting Information File 1 for details). Thus, based on the distinctive NOE patterns of phenyl resonances, the two diastereomers (cis

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• possessing a Z geometry, as evinced by a NOE interaction between Hd and the methyl group. The cis relationship between the OH group and the pyrrolidine ring, resulting from the chemo- and stereoselective syn reduction of the carbonyl group, was evinced by NOESY-1D experiments showing intense NOE effects

• rod, disc and sphere, respectively. Chemical structure of representative approved drugs containing a spirocyclic moiety. Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36, Z rotamer, using ab initio calculation at the HF/3-21G* level. PCA plot

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• orientation of the anomeric hydroxy group was proven by NOESY correlations between the H-2 proton and both geminal protons of the CH2P unit. A strong NOE was also observed for the upfield-shifted doublet of doublets at 1.71 ppm of the methylene group, which had an additional NOE correlation with the broad

• % yield [29]. At this stage, the Z-configuration of the enol ether was unambiguously assigned on the basis of NOESY experiments. Specifically, NOE correlations were seen between the olefinic proton and the methylene protons of a benzyl group. The position of the 2-O-benzyl group was assigned on the basis

Chiral terpene auxiliaries V: Synthesis of new chiral γ-hydroxyphosphine oxides derived from α-pinene

• Anna Kmieciak and
• Marek P. Krzemiński

Beilstein J. Org. Chem. 2019, 15, 2493–2499, doi:10.3762/bjoc.15.242

• = 9.5 Hz), 131.10 (d, J = 9.5 Hz), 131.61 (d, J = 98.6 Hz), 131.82 (d, J = 3.2 Hz), 131.88 (d, J = 2.4 Hz), 133.61 (d, J = 100.1 Hz); 31P NMR (162 MHz, CDCl3) δ 36.03; anal. calcd for C23H29O2P: C, 74.98; H, 7.93; found: C, 75.08; H, 7.77. NOE effects in molecules 16 and 18. Synthesis of (1R,2R,4S,5R)-3

Experimental and computational electrochemistry of quinazolinespirohexadienone molecular switches – differential electrochromic vs photochromic behavior

• Eric W. Webb,
• Jonathan P. Moerdyk,
• Kyndra B. Sluiter,
• Benjamin J. Pollock,
• Amy L. Speelman,
• Eugene J. Lynch,
• William F. Polik and
• Jason G. Gillmore

Beilstein J. Org. Chem. 2019, 15, 2473–2485, doi:10.3762/bjoc.15.240

• electrolysis or photolysis as indicated through electrochemical analysis was further supported through NMR. Previous work [21] had conclusively shown through 1H NOE NMR spectroscopy that the LW isomers resulting from photolysis of 3a and 3b were 4a and 4b, which open toward the more electron-deficient

• heteroaromatic ring of the quinoline and away from the R group. Unfortunately, efforts to obtain a sufficient quantity of the electrogenerated LW form of 3a (i.e., 4a or 5a) for definitive 1H NMR spectra or NOE experiments were not successful However, both UV–vis and electrochemical measurements indicated small

• thermal LW forms are the same isomer 5a, while it is the pLW isomer 4a that grows in upon photolysis (Figure 3c, dashed green; Figure 5b). Furthermore, modest NOE enhancements can be observed even on the small amounts of 5a present in these solutions. These NOEs, while weak, did aid in assigning the peaks