Synthesis of pyrrolo[2,1-f][1,2,4]triazin-4(3H)-ones: Rearrangement of pyrrolo[1,2-d][1,3,4]oxadiazines and regioselective intramolecular cyclization of 1,2-biscarbamoyl-substituted 1H-pyrroles

• Kkonnip Son and
• Seong Jun Park

Beilstein J. Org. Chem. 2016, 12, 1780–1787, doi:10.3762/bjoc.12.168

• regioselectivity. NOE analysis of representative examples (11a/11d and 12a/12d). Supporting Information Supporting Information File 556: Experimental and analytical data.

Three-component synthesis of highly functionalized aziridines containing a peptide side chain and their one-step transformation into β-functionalized α-ketoamides

• Lena Huck,
• Juan F. González,
• Elena de la Cuesta and
• J. Carlos Menéndez

Beilstein J. Org. Chem. 2016, 12, 1772–1777, doi:10.3762/bjoc.12.166

• all cases, the reaction proceeded with full diastereoselectivity, affording the product with a cis relationship between the aryl substituent and the peptide side chain as shown by NOE studies, which are summarized in Figure 1 for compound 2f. One example of a reaction leading to an alkyl substituent

• providing a fast and efficient access to an important pharmacophore in the design of enzyme inhibitors. Furthermore, the aziridines could also be transformed into α,β-diketoamides, which were suitable precursors for nitrogen heterocycles bearing a peptide side chain. NOE effects in compound 2f. Summary of

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• protons at C4’. Based on the coupling constant and nOe studies (Figure 2), the signal at δ 2.30 was assigned to the axially oriented proton at C4’. As this proton appeared as a triplet with a large coupling constant of 12.7 Hz (vicinal and geminal), the adjacent C5’ proton therefore assigned axial

Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe

• Motoyuki Isoda,
• Kazuyuki Sato,
• Yurika Kunugi,
• Satsuki Tokonishi,
• Atsushi Tarui,
• Masaaki Omote,
• Hideki Minami and
• Akira Ando

Beilstein J. Org. Chem. 2016, 12, 1608–1615, doi:10.3762/bjoc.12.157

• . NaCl and dried over MgSO4. The solvent was removed in vacuo, and the residue was purified by column chromatography to give the corresponding syn-azetidin-2-one. The stereochemistry of the products were determined by the NOE between the CH3 and C6H5 groups on the azetidin-2-one ring and the coupling

The hydrolysis of geminal ethers: a kinetic appraisal of orthoesters and ketals

• Sonia L. Repetto,
• James F. Costello,
• Craig P. Butts,
• Joseph K. W. Lam and
• Norman M. Ratcliffe

Beilstein J. Org. Chem. 2016, 12, 1467–1475, doi:10.3762/bjoc.12.143

• additional two-fold rate acceleration of 14 (kH+ = 27.9 M−1 s−1) with respect to 10–11 is ascribed to the relief of transannular compression involving the C(4/5)–Me and Me–C(2) groups, which nOe studies suggest are near to each other in space (see structure 14, Figure 3). The reactivity of C(2) substituted

• respect to 8 [18] and 16 [23], respectively (see Experimental section). Stereoelectronic contributions to hydrolysis; (a) conformationally constrained 1,3-dioxane orthoester; (b) Newman projection of five-membered ZICMED viewed C(4)→C(5). The assignment of 10–11 and 14 via nOe [viewed C(4)→C(5)]. Newman

On the mechanism of imine elimination from Fischer tungsten carbene complexes

• Philipp Veit,
• Christoph Förster and
• Katja Heinze

Beilstein J. Org. Chem. 2016, 12, 1322–1333, doi:10.3762/bjoc.12.125

• , 13C,1H HMBC techniques), all 1H and 13C NMR resonances of W(CO)5(E-2) are assigned based on coupling patterns and NOE contacts (Experimental section and Supporting Information File 1). Only the resonances of the unsubstituted C5H5 ligands (H1, H10 and C1, C10) could not be discriminated. The proton

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• (Figure 1). A nuclear Overhauser effect (NOE) was observed between the benzyl protons and the aromatic protons of the antimony p-tolyl groups. Other triazole 3 showed similar NOE signals between the 1-N-substituent protons and the p-tolyl protons. The reaction mechanism of the cyclization is unclear at

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• corresponding products 271 and 272 were isolated in 52–61% yields and their nOe analysis revealed the geometry of the alkene bonds to be E . A tandem 1,4–1,2 addition of dimethyl trimethylsilyl phosphite (DMPTMS, 273) to diazaheterocyclic compounds under microwave irradiation in acidic medium led to

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