Biradical vs singlet oxygen photogeneration in suprofen–cholesterol systems

• Fabrizio Palumbo,
• Francisco Bosca,
• Isabel M. Morera,
• Inmaculada Andreu and
• Miguel A. Miranda

Beilstein J. Org. Chem. 2016, 12, 1196–1202, doi:10.3762/bjoc.12.115

• , 13C, HSQC and NOEDIFF) and mass spectrometry analysis, including high-resolution measurements. Because of the rigidity of the steroidal skeleton, NOE experiments were necessary to assign the stereochemistry of the new chiral centers generated upon photocyclization. In both photoproducts, the most

• -benzoylthiophene (BZT). Chemical structure of tiaprofenic acid (TPA) and suprofen (SP). Chemical structures of dyads 1–3. Diagnostic NOE interactions in compounds 4 and 5. Decrease of the absorbance at 290 nm upon irradiation in CH2Cl2 under N2 for 1 (red circles), 2 (black squares) and 3 (blue triangles) as a

Unusual traits of cis and trans-2,3-dibromo-1,1-dimethylindane on the way from 1,1-dimethylindene to 2-bromo-, 3-bromo-, and 2,3-dibromo-1,1-dimethylindene

• Rudolf Knorr,
• David S. Stephenson,
• Ernst Lattke,
• Petra Böhrer and
• Jakob Ruhdorfer

Beilstein J. Org. Chem. 2016, 12, 1178–1184, doi:10.3762/bjoc.12.113

• -H) cis interproton relationships. Such distances may be estimated through nuclear magnetic Overhauser enhancements (NOE). As expected if trans-1 populates predominantly the 2ax-H,3ax-H conformation shown in Scheme 1, our one-dimensional NOE difference experiments revealed an approximately eight-fold

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

• Sebastian Bretzke,
• Stephan Scheeff,
• Felicitas Vollmeyer,
• Friederike Eberhagen,
• Frank Rominger and
• Dirk Menche

Beilstein J. Org. Chem. 2016, 12, 1111–1121, doi:10.3762/bjoc.12.107

• model substrate 19 (see Scheme 4) no selectivity was observed in this coupling, which could also not be modified by other solvents. Possibly this may be due to the missing Cbz group of 5 as compared to 19. The configuration of both products was assigned by NMR methods based on characteristic NOE

Efficient syntheses of climate relevant isoprene nitrates and (1R,5S)-(−)-myrtenol nitrate

• Sean P. Bew,
• Glyn D. Hiatt-Gipson,
• Graham P. Mills and
• Claire E. Reeves

Beilstein J. Org. Chem. 2016, 12, 1081–1095, doi:10.3762/bjoc.12.103

• stereochemical assignment for (Z)-9 and (E)-10 was important. Homonuclear two-dimensional NOE spectroscopy (NOESY) was used to explore the C=C double bond configuration. (E)-10 displayed two NOE interactions between the alkene proton and the methylene groups of the adjacent -CH2OH and -CH2ONO2 (see ‘double

• -headed arrows’, Scheme 9). In (Z)-9 the alkene proton had an NOE interaction with the adjacent CH3 (see red arrow, Scheme 9) and the methylene of the -CH2ONO2 group likewise had an observable interaction with the CH3 (see purple arrow). However, unlike (E)-10 no interaction was observed between the

Strecker degradation of amino acids promoted by a camphor-derived sulfonamide

• M. Fernanda N. N. Carvalho,
• M. João Ferreira,
• Ana S. O. Knittel,
• Maria da Conceição Oliveira,
• João Costa Pessoa,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2016, 12, 732–744, doi:10.3762/bjoc.12.73

• such a way that H4B (3.28 ppm) gives NOE with H4A (2.43 ppm) and H3A (4.81 ppm) (Supporting Information File 1). The 1H NMR spectrum further supports two distinct oxoimine units in the same molecule. No N–H signals were detected conceivably due to traces of water that promotes N–H fast (on the NMR

• isomer. The optimized structure of the (S)-3A isomer is displayed in Figure 5. Assuming that to observe NOE effects in the 2D NMR spectra a distance lower than ca. 3 Å between the hydrogen atoms is required, the calculated structures indicate that H3A should show a strong NOE to H10A (one of the methyl

• )-3A and (R)-3A isomers are expected; the calculated distance of H3A to H4B in the second camphor moiety is 2.181 Å in the isomer with (S)-3A and 2.459 Å in (R)-3A, i.e., they do not differ sufficiently to allow for a decision between the isomers on the basis of NOE effects. Thus, the strong cross peak

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• ). NOE correlations (Figure 4) usually found in the β-D-glucopyranosyl core were also revealed between the anomeric proton H-1’ (δ 4.28), H-3’ (δ 3.38), and H-5’ (δ 3.30). The relative configuration of the aglycone was tentatively determined based on NOESY contacts observed between H-12, H-10, and H-3

• centers in the aglycone was tentatively assigned as those previously reported for the trixane skeleton. Relative configurations of compound 2 turned to be similar as that of compound 1 since H-12 (δ 1.05) revealed NOE contact (Figure 4) with H-3 (δ 4.43) and H-10 (δ 1.90) likewise, H-13 (δ 1.10) showed

Stereoselective amine-thiourea-catalysed sulfa-Michael/nitroaldol cascade approach to 3,4,5-substituted tetrahydrothiophenes bearing a quaternary stereocenter

• Sara Meninno,
• Chiara Volpe,
• Giorgio Della Sala,
• Amedeo Capobianco and
• Alessandra Lattanzi

Beilstein J. Org. Chem. 2016, 12, 643–647, doi:10.3762/bjoc.12.63

• secondary amine moiety greatly affects the stereochemical outcome of the process. The relative configuration of diastereoisomers 7a/8a/9a was established by NOESY and NOE analysis on diastereoisomerically pure 7a and on a diastereoisomeric mixture of compounds 8a and 9a (see the Supporting Information File

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• the ethyl ester of 11 was determined NMR spectroscopically including nOe experiments (see Supporting Information File 1). Next, vinyl iodide 10 was subjected to amidation with L-alanine methylate (resembling position 2 in myxovalargin) using the reagent system PyAOP, HOAt, DIPEA to yield amide 12

• the olefinic double bond (Scheme 6). We based the stereochemical assignment on NMR spectroscopy which included nOe experiments. Conclusion In conclusion, we report on the synthesis of dehydrovaline and dehydroisoleucine-containing oligopeptides as found in the peptide antibiotic myxovalargin using a C

• 44. nOe assignments (tripeptide corresponds to amino acids 11–13 in myxovalargin (1)). Formation of amide 12 and optimization of C–N cross coupling reaction. Supporting Information Supporting Information File 48: Syntheses and analytical descriptions of reagents and peptides and copies of 1H and 13C

Diastereoselective synthesis of new O-alkylated and C-branched inositols and their corresponding fluoro analogues

• Charlotte Collet,
• Françoise Chrétien,
• Yves Chapleur and
• Sandrine Lamandé-Langle

Beilstein J. Org. Chem. 2016, 12, 353–361, doi:10.3762/bjoc.12.39

• in 53% and 38% yields, respectively. The configuration of the diastereoisomers was determined with 1H and nOe NMR experiments (Figure 2). For compounds myo-14 and myo-15 correlations between H1/H3 and the alkenyl proton of the arm were observed confirming the equatorial orientation of the substituent

• candidates for PET imaging experiments. Their potential use as radiotracers is under current investigation. Structures of targeted synthetic inositol derivatives. nOe correlations for C-alkenylated inositol intermediates. Synthesis of O-alkylated inositol derivatives 1. Reagents and conditions: a) NaBH4

Tandem processes promoted by a hydrogen shift in 6-arylfulvenes bearing acetalic units at ortho position: a combined experimental and computational study

• Mateo Alajarin,
• Marta Marin-Luna,
• Pilar Sanchez-Andrada and
• Angel Vidal

Beilstein J. Org. Chem. 2016, 12, 260–270, doi:10.3762/bjoc.12.28

• 5 and 6, was easily accomplished by using the habitual analytical and spectroscopic techniques, whereas the distinction between each two regioisomers is basically supported by 1H NMR NOE difference experiments. For the major isomers 5 enhancements of the signals due to the H-C2 and CH2-OAr protons

A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• coworkers reported that a cyclic bisnaphthalenediimide formed a complex with d(CGGTACCG)2 that provided a well-resolved NMR and clear NOE signals between the linking chains and both the major and minor grooves [50]. Additional studies on this class of DNA ligands as part of an excellent review of other

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• shows this interaction as NOE crosspeaks between the inner hydrogens (H3 and H5) of the CD cavity and between the aromatic or double bond hydrogens of the cinnamyl moiety. In the spectra of both regioisomers intense correlations were observed between the phenyl protons (7.2–7.5 ppm) and the protons of

• cavity and in both molecules this inclusion phenomenon takes place from the secondary side of the CD cavity. Supramolecular structures of 2-O-Cin-α-CD and 3-O-Cin-α-CD characterized by a 1H NMR dilution experiment The observed NOE signals proved the close spatial proximity of the inner protons of the CD

• cavity and the aromatic and double bond protons of the cinnamyl moiety. However these experimental evidences do not unambiguously confirm the existence of the intermolecular interaction, because self-inclusion processes cannot be excluded. In order to prove our assumption that the NOE correlations arise

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• describing the real structure of CD inclusion complexes and indicating the exact positioning of guest inside the CD cavity. It is based on the observation of the nuclear Overhauser effect (NOE) between the protons of the guest and that of the CD that take action in the inclusion process [42]. The presence of

• NOE cross correlation peaks between the protons of guest and CD indicates space couplings and confirms that protons are close in space (<4Å). We performed 2D ROESY experiments for inclusion complexes of both β-CD/1 and β-CD/2 prepared at equimolar ratios. Partial contour plots of the ROESY spectra of

• inclusion complexes are shown in Figure 5 and Figure 6 for 1 and 2, respectively. First, the absence of any NOE cross correlation peaks between 1 and 2 protons and H-1, H-2 and H-4 protons of β-CD ruled out any significant interaction between guests and the external surface of β-CD at equilibrium in

Assembly of synthetic Aβ miniamyloids on polyol templates

• Sebastian Nils Fischer and
• Armin Geyer

Beilstein J. Org. Chem. 2015, 11, 2646–2653, doi:10.3762/bjoc.11.284

• correlation. Nuclear magnetic resonance spectroscopy is the analytical method of choice not only to characterize the conversion of template and peptide or to differentiate regioisomers, but also because it can detect noncovalent interactions between peptide strands by NOE contacts or other techniques. The

• , instead of a protecting group, the azide serves as a precursor of the amine which is necessary for the fragment coupling of 5 to oligomeric templates. Along this strategy, tetrapeptide 9 was obtained which represents a bis-dihydroxylated template. Hot=Tap oligomers are suitable for NOE-sequencing along

Exploring architectures displaying multimeric presentations of a trihydroxypiperidine iminosugar

• Camilla Matassini,
• Stefania Mirabella,
• Andrea Goti,
• Inmaculada Robina,
• Antonio J. Moreno-Vargas and
• Francesca Cardona

Beilstein J. Org. Chem. 2015, 11, 2631–2640, doi:10.3762/bjoc.11.282

• assignments 2D spectra were measured (COSY, HSQC, NOESY, and NOE as necessary). Small scale microwave-assisted syntheses were carried out in a microwave apparatus for synthesis (CEM Discover) with an open reaction vessel and external surface sensor. IR spectra were recorded with a BX FTIR Perkin-Elmer system

Bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina lacunosa

• Qun Göthel,
• Thanchanok Sirirak and
• Matthias Köck

Beilstein J. Org. Chem. 2015, 11, 2334–2342, doi:10.3762/bjoc.11.254

• (2H, H-7 and H-7´) indicated a trans-hydroxyspiroisoxazoline ring which was supported by a W-coupling between the olefinic proton H-5 and the methine proton H-1 (4J ~ 0.7 Hz) [28][33]. An NOE was also observed between δH 5.54 (19-OH) and δH 6.37 (1´-OH) suggested that both hydroxy groups are on the

• configuration of spiroisoxazoline moieties were assigned as 1,1´-(R),6,6´-(S) (Figure 1). The absolute configuration of C-19 was assigned as 19-(R) according to NOE data which is in agreement with the proposed configuration by Molinski and co-workers [34][36]. The configuration of C-19 of fistularin-3 (5) was

• ) and 3.61 (C-7) as well as between 6.56 (H-6) and 3.17 (H-7) suggesting a trans-hydroxyspiroisoxazoline ring similar to compound 1. An NOE was also observed between δH 5.72 (11-OH) and 1-OH indicating the same planar alignment of both hydroxy groups. The absolute configuration of spiroisoxazoline

Conformational equilibrium in supramolecular chemistry: Dibutyltriuret case

• Karina Mroczyńska,
• Małgorzata Kaczorowska,
• Erkki Kolehmainen,
• Ireneusz Grubecki,
• Marek Pietrzak and
• Borys Ośmiałowski

Beilstein J. Org. Chem. 2015, 11, 2105–2116, doi:10.3762/bjoc.11.227

• temperature is caused by fast in NMR time-scale equilibrium between various forms. The NOE experiments for 1 (and associated 1) at lowered temperatures did not gave any unequivocal data regarding the shift of equilibrium towards any form. This excludes the existence of the dimer or multimer of 1a as the major

Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• reasonably assigned on the basis of NOE interactions between H-5 and the two H-4 hydrogens, Figure 3. Furthermore, for compound 3a it was possible to observe diagnostic NOE interactions between NH and the three cis hydrogens in position 1, 2 and 4, Figure 3. On the contrary, for compound 3'a in Figure 3, NH

• NOE interactions involve cis hydrogens at positions 1 and 4 and the aromatic p-tolyl hydrogens, Figure 3. Finally, tetrahydrocarbazoles 3a,b,d and 3'a were selected as substrates to test the reactivity of our compounds under hydrolytic conditions to obtain the deprotection of indole nitrogen and the

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• mass spectrometry. The H,H and H,C connectivities were determined by COSY and HSQC experiments, while the conformation was determined by nOe through t-ROESY experiments. Figure 5 shows the 1H NMR spectrum of 1. Three signals are present in the aliphatic region: H(2,4)ax protons as a double signal at δ

• through nOe (Figure 6a). In 4, nOe was observed among H(4)ax, H(5)eq, and H(2)ax, and for H(7)ax with H(6)eq and H(8)eq. Furthermore, nOe was observed among H(5)eq, H(6)ax, and H(6)eq (Figure 6b). Based on the nOe values and 3JH,H coupling constants, the solution conformation was determined using the

• decoupling experiment both with and without nOe at 125.76 MHz using a spectral width of 31446.54 Hz, an acquisition time of 0.8 s, 32678 points, 2052 scans, and a recycle delay of 0.1 s. The non-decoupled 13C NMR spectra with nOe were recorded with a spectral width of 39308.17 Hz, a resolution of 0.9 Hz, and

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• be too distant from each other to show an nOe. In any cyclopentane conformation this would be the case for hydrogen atoms located in 1,3-trans-position. Thus, the presence of a NOESY cross peak would exclude 1,3-trans-orientation of the respective hydrogens. In diastereomers 6, 7, and 8 there were

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• -psicofuranose (11) as the suitable substrate for thioglycosylation. Attempts to determine the configuration at the anomeric center in compounds 10 or 11 by employing NOE NMR technique were ambiguous. Although both derivatives 10 and 11 were crystalline solids, it was not possible to obtain suitable crystals for

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• -exo. After chromatographic separation, NOESY experiments indicated that 10b-endo shows two nOe correlations: one between H1 and H2 (which indicates the cis-fusion of the two cycles) and another one between H1 and the aromatic proton H3. These two nOe interactions, together with the absence of a

• correlation between H1 and H4 indicated that the phenyl ring and H1 display a cis relationship. Additionally, compound 10b-exo only showed an nOe correlation between H1 and H3 (Figure 1). For the rest of compounds 10, an analogous stereochemical outcome was assumed. Conclusion In conclusion, a new tandem CEYM

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• less stable nonanomeric form [23]. To determine the configuration at 9-C and elucidate the conformation of 2, nOe analysis was performed (Tables SI1 and SI2, in Supporting Information File 1), followed by molecular modelling. Very strong nOe correlations between 2-H, 5-H and 10-H observed in both DMSO

• -d6 and CDCl3 attest to their close spatial proximity (2.0–2.6 Å). Other characteristic observed nOe interactions are: very strong 4-H↔6-Me, 8-Me↔10-Me, 3-H↔4-Me, 5-H↔7-Hax, 5-H↔6-Me, 5-H↔10-Me correlations and a weak interaction between 4-Me and 5-H. To simplify the generation of the three

• 5C8 conformation which explains the observed system of nOe correlations between 2-H, 5-H and 10-Me (2.2–2.9 Å), as well as 8-Me↔10-Me (2.7 Å) and 11-H ↔14b-H (2.8 Å) interactions, all shown in Table SI3, in Supporting Information File 1. The coupling constants 3J8-H,7-Ha and 3J8-H,7-Hb (one strong

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• could not detect any cyclopentenone. Instead, we were amazed to isolate the rearranged ketone 17 (entry 3, Table 1). Indeed, 4,4-diarylnaphthalen-1-ones are highly unusual compounds, whose synthesis is rarely described in literature [11]. The structure of 17 was confirmed by NOE and key HMBC

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• integration of the aromatic protons and benzylic protons to 15 and 4, respectively, indicate the abstraction of the H-2 and elimination of the benzyloxy group at C-3. The absence of a coupling between H-1 and H-5 in the NOE NMR spectrum confirmed the α-configuration of the glycosidic bond at C-1. The