Switchable highly regioselective synthesis of 3,4-dihydroquinoxalin-2(1H)ones from o-phenylenediamines and aroylpyruvates

• Juraj Dobiaš,
• Marek Ondruš,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2017, 13, 1350–1360, doi:10.3762/bjoc.13.132

• chain like in 3 (Scheme 1). This knowledge, in combination with a simple NOE experiment (interaction H-N(4) with a narrow doublet of H-C(5) (ca 1.5 Hz) in SYN or H-N(4) with a broad doublet of H-C(5) (8.4 Hz) in ANTI, allows for the determination of the regioisomerism more effectively (no need for HMBC

• ), in the case that the NOE experiment was performing (which was not always the case). The same approach to distinguish regioisomers can be applied on space interactions between H-N(1) and H-C(8) signals (NOESY in Figure 2 or for NOE see the Supporting Information File 1). Finally, all six regioisomeric

• -dihydroquinoxaline-2(1H)-ones. Their ANTI (17) or SYN (16) structures were assigned by complex 2D NMR techniques (HSQC, NOESY and HMBC) or by a proposed simplified method (NOE interaction between higher 1H NMR (DMSO-d6) shifted H-N(4), bonded by intramolecular hydrogen bond, and H-C(5) or interaction of lower

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• desired (Z,E,Z)-configured triene 19. Again, we did not encounter formation of stereoisomers in the triene unit. The configuration of the triene was unequivocally assigned by analysis of coupling constants (J) and by measuring nuclear Overhauser effects (nOe). Finally, desilylation and global

New tricks of well-known aminoazoles in isocyanide-based multicomponent reactions and antibacterial activity of the compounds synthesized

• Maryna V. Murlykina,
• Maryna N. Kornet,
• Sergey M. Desenko,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Aleksander A. Brazhko,
• Vladimir I. Musatov,
• Erik V. Van der Eycken and
• Valentin A. Chebanov

Beilstein J. Org. Chem. 2017, 13, 1050–1063, doi:10.3762/bjoc.13.104

• analysis (Figure 3). In the case of compounds 9 the presence of NOE between the signals of the methyl group and the CH group in the isoxazole moiety allowed to distinguish closely located signals of two CH groups (Figure 4). Ultimately, the structure of compounds 9 was proven by an X-ray analysis of

• . Selected data of NOE and HSQC experiments for compound 9d. Molecular structure of N-(2-(tert-butylamino)-1-(4-chlorophenyl)-2-oxoethyl)-N-(5-methylisoxazol-3-yl)-3-phenylpropiolamide (9e) (X-ray diffraction data). Non-hydrogen atoms are presented as thermal ellipsoids with 50% probability. Aminoazoles in

Cycloheximide congeners produced by Streptomyces sp. SC0581 and photoinduced interconversion between (E)- and (Z)-2,3-dehydroanhydrocycloheximides

• Li Yang,
• Ping Wu,
• Jinghua Xue,
• Huitong Tan,
• Zheng Zhang and
• Xiaoyi Wei

Beilstein J. Org. Chem. 2017, 13, 1039–1049, doi:10.3762/bjoc.13.103

• pseudo-axial positions and on the same face of the cyclohexenone ring. This was further corroborated by the presence of strong NOE correlations of H3-8 with both H5ax and H5eq and of H5eq with both H6 and H4 in the NOESY spectrum (Figure 2). It was also in agreement with no NOE correlation being detected

• with the diagnostic NOE interaction of Hα/H5eq observed in the NOESY spectrum. In turn, (4R,6R,αR)-1 afforded the dominant conformers (accounting for about 82% equilibrium populations), as represented by the global energy minimum (R)-1a1 (Figure 2), having an anti relationship (ΦH6/Hα ≈ 174°) between

• Hα/H6, which were inconsistent with the small JH6/Hα value (4.3 Hz) and the absence of an NOE correlation between Hα/H5ax in the experimental spectra. Accordingly, the relative configuration of 1 was assigned to be 4R*,6R*,αS*. In order to determine the absolute configuration, the low-energy

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• , and 2D NMR spectra (see Supporting Information File 1 for details). The anomeric α-configuration of compound 2 was confirmed by analysis of the NOE effects between the C-1 hydrogen and the C-5 hydrogen. With the ketoheptose building block 2 in hand, we turned our attention to the synthesis of D-manno

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• 1D NOESY experiments (Figure 4). First, the hydrogen H3’ in 13a and 13b was selectively excited. The nOes observed for compound 13a are in the following order of decreasing intensity: CH3 > H5’a > H5’b-H4’ > H1’ confirming that CH3 and H3’ are spatially close. In the case of 13b the nOe intensities

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study

• Franca Castiglione,
• Fabio Ganazzoli,
• Luciana Malpezzi,
• Andrea Mele,
• Walter Panzeri and
• Giuseppina Raffaini

Beilstein J. Org. Chem. 2017, 13, 714–719, doi:10.3762/bjoc.13.70

• 7, 20131 Milano, Italy 10.3762/bjoc.13.70 Abstract Tricyclic fused-ring cyclobenzaprine (1) and amitriptyline (2) form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both 1

• . Keywords: amitriptyline; β-cyclodextrin; crystal structure; cyclobenzaprine; molecular dynamics simulations; NOE; Introduction The present paper reports on a multidisciplinary approach [1][2] based on single crystal X-ray diffraction, solution NMR spectroscopy and molecular dynamics (MD) simulations with

• intermolecular contacts with H5’ and H3’ of the β-CD, indicating that the ring system of 1 is deeply inserted into the cavity of the β-CD. The selective NOE between H12 and H3’ suggests that the alkylammonium chain is protruding out of the β-CD cavity from the secondary OH rim. The analysis of intermolecular

Isoxazole derivatives as new nitric oxide elicitors in plants

• Anca Oancea,
• Emilian Georgescu,
• Florentina Georgescu,
• Alina Nicolescu,
• Elena Iulia Oprita,
• Catalina Tudora,
• Lucian Vladulescu,
• Marius-Constantin Vladulescu,
• Florin Oancea and
• Calin Deleanu

Beilstein J. Org. Chem. 2017, 13, 659–664, doi:10.3762/bjoc.13.65

• experiments. The 3,5-disubstitution was also experimentally proven by NOE experiments which indicated through space interaction between the H-4 proton and the protons from both 3- and 5- substituents. Biological activity We investigated the inductor effects of 3,5-disubstituted isoxazoles 6–11 on NO and

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• constants to the vicinal axial H-2β and H-4β of 12 Hz and to the equatorial H-2α and H-4α of 6 Hz. NOE correlations of H-3 to H-1α, H-2α and H-4α indicate thus an α-orientation of axial H-3 and a β-orientation of the equatorial hydroxy group at C-3. The identical 13C NMR shift of C-3 (δC 68.0) with the

• -orientation of the substituent at the bridge head carbon C-5. NOEs between the resonances for H-2β as well as H-1β to H3-19 showed the latter to be β-orientated, and thus the trans configuration of the decaline system. The 1H NMR signal at δH 3.66 for H-6 exhibited NOE correlation with H-4α (δH 1.70, m

• ) indicating β-orientation of the equatorial OH-group at C-6. Contrary to the reported epoxy-secosteroid by Naz et al. [22], no NOE was observed between the resonances of H-6 and β-oriented H3-19 confirming the β-orientation of the hydroxy group at C-6 (see Figure 5). NOE correlations between H3-19 and H-8, as

Multicomponent synthesis of spiropyrrolidine analogues derived from vinylindole/indazole by a 1,3-dipolar cycloaddition reaction

• Manjunatha Narayanarao,
• Lokesh Koodlur,
• Vijayakumar G. Revanasiddappa,
• Subramanya Gopal and
• Susmita Kamila

Beilstein J. Org. Chem. 2016, 12, 2893–2897, doi:10.3762/bjoc.12.288

• which showed NOE interactions between H1 and H2 on the asymmetric carbon atoms correlated to the syn-configuration (Figure 1). Upon irradiation of H1 the NOE enhancement was observed for H3 and H4 and the same was observed by irradiation of the ring-junction proton H2. The regioselectivity of cyclic

• compounds that could find use in different areas of chemistry. The advantages of the synthesis described are its ease of execution, short reaction times and diversity of the products synthesized. NOE interactions in compound 8c supporting the stereochemical assignments for 8a–k. H1 and H2 on the asymmetric

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• -range coupling was detected between H9 and C18 (43.40 ppm), the carbon atom of the benzyl group at N2. NOE experiments support the assigned stereochemical relationships. In agreement with the internuclear distance values, obtained from computational data (see Supporting Information File 1), irradiation

• of H9, in compound 6a, induces a positive NOE effect for methylene protons at C7 (4.25 and 4.06 ppm), while, for 7a, a NOE enhancement was observed for methylene protons at C18 (5.06 and 4.82 ppm) (Figure 3). Furthermore, X-ray diffraction measurements confirm the structural assignment. Unfortunately

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• [68]. NMR information has been used in many studies to intelligently guide protein structure prediction [69][70][71]. NMR Nuclear Overhauser Effect (NOE) data and chemical shifts have been used in combination with Rosetta ab initio structure prediction to obtain better protein structure predictions

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• ) were isolated from Streptomyces hygroscopicus LL-AC98 in 2002 [7] and their structures were elucidated using mass spectrometry and extensive NMR analysis. The absolute stereochemistry was proposed following degradation and nOe studies. The configuration of the β-methylphenylalanine stereocentre was

Diels–Alder reactions in confined spaces: the influence of catalyst structure and the nature of active sites for the retro-Diels–Alder reaction

• Ángel Cantín,
• M. Victoria Gomez and
• Antonio de la Hoz

Beilstein J. Org. Chem. 2016, 12, 2181–2188, doi:10.3762/bjoc.12.208

• and samples were taken every hour, being directly analyzed by 1H NMR. Reaction products were isolated by HPLC using mixtures of H2O/MeOH/MeCN (45:50:5). Identification of these products was carried out by NMR techniques (1H, 13C, DEPT, COSY, HETCOR and NOE) being the spectral data fully coincident

Varioloid A, a new indolyl-6,10b-dihydro-5aH-[1]benzofuro[2,3-b]indole derivative from the marine alga-derived endophytic fungus Paecilomyces variotii EN-291

• Peng Zhang,
• Xiao-Ming Li,
• Xin-Xin Mao,
• Attila Mándi,
• Tibor Kurtán and
• Bin-Gui Wang

Beilstein J. Org. Chem. 2016, 12, 2012–2018, doi:10.3762/bjoc.12.188

• NOE correlation between H-2 and 3-OMe led to recognition that these protons adopt cis orientation. In order to elucidate the absolute configuration of 1, solution TDDFT-ECD protocol [14][15] was carried out on the arbitrarily chosen (2R,3R) enantiomer. The preliminary conformational search at MMFF

Synthesis and NMR studies of malonyl-linked glycoconjugates of N-(2-aminoethyl)glycine. Building blocks for the construction of combinatorial glycopeptide libraries

• Markus Nörrlinger,
• Sven Hafner and
• Thomas Ziegler

Beilstein J. Org. Chem. 2016, 12, 1939–1948, doi:10.3762/bjoc.12.183

• assignment of the amidic doublets. Stronger NOE crosspeaks between the methylene protons of the side chain (3.20 ppm) and the methylene protons of the PNA backbone (3.93 ppm) indicated that the distance between these protons should be shorter in comparison to the distance of the protons with a chemical shift

• temperature are marked. A) Missing correlation between the amidic proton and the methylene or 2-aminoethyl protons of the PNA backbone; B) Observed NOE-correlations of PNA building block 1a. Synthesis of building blocks 1a–d and 2a–d (a stands for D-glucose, b stands for D-galactose, c stands for N

Mechanistic investigations on six bacterial terpene cyclases

• Patrick Rabe,
• Thomas Schmitz and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2016, 12, 1839–1850, doi:10.3762/bjoc.12.173

• methyl groups C-14 and C-15 at the quarternary carbons C-10 and C-4, respectively (cross peaks between H-14 and C-1, C-9 and C-10 and between H-15 and C-3, C-4 and C-5, Figure 2b). Key NOE correlations between H-1 and H-6 confirmed the cis-decalin system, while NOE correlations of H-14 and H-7 finally

• two-dimensional NOESY spectroscopy. Key correlations between H-15 and H-6, H-6 and H-8α (0.76 ppm), and H-8α with H-10 placed these hydrogens at the same face of the molecule, while NOE correlations between H-14 and H-5 and between H-5 and H-7 showed that these hydrogens are located at the opposite

• connectivity of the C-15 methyl group (Figure 3b). Strong NOE correlations between H-1 and H-7 and between H-6 and H-12 established the trans-decalin system. The optical rotary power was determined as [α]D22 = −32.3 (c 0.05, CH3OH) indicating the absolute configuration of (1S,6S,7R)-(−)-γ-cadinene which is the

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