De novo synthesis of D- and L-fucosamine containing disaccharides

• Daniele Leonori and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 332–341, doi:10.3762/bjoc.9.38

• the desired silylated products 7a–c (Table 1). The alkene geometry was confirmed as Z by nuclear Overauser effect (nOe). Treatment of 7a–c with TBAF and CuI delivered 3 in high yields. Generally, BnMe2SiH has been found to be optimal for these transformations [54][55]. In our hands however, the best

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• separation. The 6S,12aS-configuration of the prevailing diastereoisomer was easily ascertained by application of the protocol of Ungemach et al. [45] on the 13C NMR spectrum of compound 2 and, conclusively, by the observation of an intense NOE contact between H-6 and H-12a in the 2D NOESY spectrum

Dipyrazolo[1,5-a:4',3'-c]pyridines – a new heterocyclic system accessed via multicomponent reaction

• Wolfgang Holzer,
• Gytė Vilkauskaitė,
• Eglė Arbačiauskienė and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2012, 8, 2223–2229, doi:10.3762/bjoc.8.251

• application of various standard NMR spectroscopic techniques, such as 1H coupled 13C NMR spectra, APT, HMQC, gs-HSQC, gs-HMBC, COSY, TOCSY, NOESY and NOE-difference spectroscopy [29]. In some cases experiments with selective excitation of certain 1H resonances were performed, such as long-range INEPT [30] and

• 2D(δ,J) long-range INEPT [31], the latter experiments having been used for the unambiguous determination of long-range 13C,1H coupling constants. With compound 2a, the tosylhydrazone of starting aldehyde 1a, (E)-configuration at the C=N double bond follows from an NOE between the iminyl-H (7.96 ppm

On the proposed structures and stereocontrolled synthesis of the cephalosporolides

• Sami F. Tlais and
• Gregory B. Dudley

Beilstein J. Org. Chem. 2012, 8, 1287–1292, doi:10.3762/bjoc.8.146

• , and it is worth noting that NOE and NOESY experiments conducted on both isomers were inconclusive in attempts to differentiate them: similar NOESY cross-peaks were observed from both isomers. We prepared the two remaining core diastereomers by similar routes (Scheme 3), starting by coupling terminal

Stereoselective synthesis of trans-fused iridoid lactones and their identification in the parasitoid wasp Alloxysta victrix, Part II: Iridomyrmecins

• Robert Hilgraf,
• Nicole Zimmermann,
• Lutz Lehmann,
• Armin Tröger and
• Wittko Francke

Beilstein J. Org. Chem. 2012, 8, 1256–1264, doi:10.3762/bjoc.8.141

• dihydronepetalactones [1], this key intermediate could be obtained via a highly diastereoselective transfer hydrogenation of the known [19] trisubstituted cyclopentene 7 with ammonium formate over palladium [1][14][15]. Starting from the aldehyde 8, the relative configuration of which had been confirmed by NOE

• configurations of the iridomyrmecins C, C' and D, D' were confirmed by NOESY experiments. In C (Figure 6, C) decisive NOEs between 1-Hb and 4a-H as well as between 1-Hb and 7-CH3 proved 4a-H and 7-CH3 to be located at the same side of the molecule. The NOE between 4-CH3 and 7a-H showed them to be geometrically

• close and the two methyl groups to be in opposite positions. In contrast, as shown in Figure 6, D' NOEs between 4a-H and 4-CH3 as well as between 4a-H and 1-Hb and furthermore between 1-Hb and 7-CH3 proved the methyl groups in D' to be at the same side of the molecule. This is confirmed by a NOE between

Design of a novel tryptophan-rich membrane-active antimicrobial peptide from the membrane-proximal region of the HIV glycoprotein, gp41

• Evan F. Haney,
• Leonard T. Nguyen,
• David J. Schibli and
• Hans J. Vogel

Beilstein J. Org. Chem. 2012, 8, 1172–1184, doi:10.3762/bjoc.8.130

• , allowing for identification of all of the backbone atoms and virtually all the side-chain atoms in gp41w-4R, gp41w-KA and gp41w-FKA (Supporting Information File 1, Figure S1). The nuclear Overhauser effect (NOE) patterns of the connections between protons in the gp41w-derived peptides are highly indicative

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• related ROESY spectrum (Table S-I, Supporting Information File 1), were used in the SA protocol. The structures possessing violations to the NOE restraints lower than 0.5 Å were selected out of the 150 generated structures. The superposition of the 18 structures with a total energy <144 kcal/mol is shown

• cycles of energy minimization by using a NOE force constant of 50 kcal/mol. The generated structures were visualized with the MOLMOL [74] (version 2K.2) program. Small unilamellar vesicles (SUVs) preparation DOPE and DOPG were purchased from Avanti Polar Lipids, Inc. (Alabaster, AL). The preparation of

Unprecedented deoxygenation at C-7 of the ansamitocin core during mutasynthetic biotransformations

• Tobias Knobloch,
• Gerald Dräger,
• Wera Collisi,
• Florenz Sasse and
• Andreas Kirschning

Beilstein J. Org. Chem. 2012, 8, 861–869, doi:10.3762/bjoc.8.96

• exchange of the tertiary carbinol at C-7 on phase-sensitive 1H–13C-correlation NMR spectra (HSQC). It needs to be noted that NOE-analysis combined with molecular modeling did not allow elucidation of the absolute configuration at C-14 for the new derivatives 13a and 13b, as it did not allow for the

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• appear as singlets at 4.85 and 4.48 ppm, respectively. Due to the unhindered rotation of the auxiliary moiety similar correlation peaks in NOE experiments were observed for both isomers. Fortunately, the minor product (3R)-3a isolated as an amorphous solid could be recrystallised from ethyl acetate

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• -substituted 2-benzyloxypyrans 3a–d are summarised in Scheme 2. The regiochemistry and relative stereochemistry of the biohydroxylated products were determined by analysis of 1H NMR coupling constants and by COSY and NOE/NOESY experiments, which identified the 5-axial and 5-equatorial hydroxylated 2-benzopyran

Intramolecular carbenoid ylide forming reactions of 2-diazo-3-keto-4-phthalimidocarboxylic esters derived from methionine and cysteine

• Marc Enßle,
• Stefan Buck,
• Roland Werz and
• Gerhard Maas

Beilstein J. Org. Chem. 2012, 8, 433–440, doi:10.3762/bjoc.8.49

• were absent from the 1H NMR spectra of the crude product mixture. For adduct 18, only one diastereomer was obtained (38% yield after workup), which, according to the observed NOE effects, has the pyrrolidinedione ring and the (CH2)2SCH3 chain in exo positions. This means that the cycloaddition has gone

• . Proposed relative configurations of the diastereomeric cyclic sulfonium ylides 12aA and 12aB. 1H NMR shifts δH (ppm) and NOE relationships are shown (E = CO2Et). Synthesis of cyclic sulfonium ylides 2; n = 0–3. Non-carbenoid formation of sulfonium ylide 4. Conditions: (a) phthalic anhydride, NEt3 (10 mol

Efficient, highly diastereoselective MS 4 Å-promoted one-pot, three-component synthesis of 2,6-disubstituted-4-tosyloxytetrahydropyrans via Prins cyclization

• Naseem Ahmed and
• Naveen Kumar Konduru

Beilstein J. Org. Chem. 2012, 8, 177–185, doi:10.3762/bjoc.8.19

• -tosyloxytetrahydropyrans were established by 1H, 13C NMR, IR, and GC–MS spectral data and elemental analysis. NOE studies of compound 3b (Table 2, entry 3) confirmed that all three substituents occupy equatorial positions on the tetrahydropyran ring. The NOE cross peaks H1/H3, H5/H3 reveal that H1, H5 and H3 are on the

• diastereoselectivity and excellent yields (95–96%). Tetrahydropyran ring containing natural products. Schematic NOE diagram of compound 3b. Plausible side products mechanism. Plausible reaction mechanism via Prins cyclization. Deprotection of the hydroxy group. Optimization of reaction yields. Preparation of

The interplay of configuration and conformation in helical perylenequinones: Insights from chirality induction in liquid crystals and calculations

• Elisa Frezza,
• Silvia Pieraccini,
• Stefania Mazzini,
• Alberta Ferrarini and
• Gian Piero Spada

Beilstein J. Org. Chem. 2012, 8, 155–163, doi:10.3762/bjoc.8.16

• suitable information on the molecular conformation in solution can be obtained from NMR-NOE experiments [31]; however, these do not provide the population of each single conformer but only the overall probability of t, g+ and g− states around bonds C(13)–C(14) and C(16)-C(17). For ease of comparison, we

• seen when the NOE probabilities are used. However, this ratio remains far from the experimental value, due to an overestimate of the magnitude of the chirality parameter Q for cercosporin (1). A possible origin of the lower twisting ability of 1 in comparison to 2, found in experiments, could be

• the geometry calculated at the M06-2X/6-31+g(d,p) level, along with conformer probability distributions inferred from NOE measurements [31]. Stars represent the Q values calculated for the X-ray structures of 1 [26][28]. For ease of comparison, the values are reported as the negative of Q for 1. Twist

Synthetic approaches to multifunctional indenes

• Neus Mesquida,
• Sara López-Pérez,
• Immaculada Dinarès and
• Ermitas Alcalde

Beilstein J. Org. Chem. 2011, 7, 1739–1744, doi:10.3762/bjoc.7.204

• Information File 1). The constitution of the acetamides 17, 19 and 23 was determined by 1D NOESY experiments in CDCl3 at 500 MHz. Thus, for each compound, irradiation at the H-2 proton of the indene core revealed a NOE for the methylene protons H-1 and H-a. For compound 23, an additional NOE was observed at

Photochemical and thermal intramolecular 1,3-dipolar cycloaddition reactions of new o-stilbene-methylene-3-sydnones and their synthesis

• Kristina Butković,
• Željko Marinić,
• Krešimir Molčanov,
• Biserka Kojić-Prodić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2011, 7, 1663–1670, doi:10.3762/bjoc.7.196

• which the expulsion of nitrogen is possible. The structure 14 (Scheme 6) was determined by additional NMR techniques, NOE and HMBC interactions, and by single crystal X-ray structure analysis (Figure 4) of the crystal formed in an NMR tube by slow evaporation of the solvent. Also, when compound 3b (cis

• protons A and B with an aromatic proton (H-2) at 7.00 ppm is seen, as well as the interaction of proton C with protons E and D. Since the NOE interaction is seen between protons A and E we concluded that protons A and E must lie on the same side of the six-membered ring. In addition, the interaction of

Multistep flow synthesis of vinyl azides and their use in the copper-catalyzed Huisgen-type cycloaddition under inductive-heating conditions

• Lukas Kupracz,
• Jan Hartwig,
• Jens Wegner,
• Sascha Ceylan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2011, 7, 1441–1448, doi:10.3762/bjoc.7.168

• yields compared to those obtained for individual steps. When starting from (E)-configured alkenes 2h and 2i, configurationally pure vinyl azides 4h and 4i with syn-orientation for both alkyl substituents were formed, as judged by nuclear Overhauser effect (NOE) experiments (Supporting Information File 1

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

• Antoine Simonneau,
• Pierre Garcia,
• Jean-Philippe Goddard,
• Virginie Mouriès-Mansuy,
• Max Malacria and
• Louis Fensterbank

Beilstein J. Org. Chem. 2011, 7, 1379–1386, doi:10.3762/bjoc.7.162

• diastereomer, and its relative stereochemistry was determined by F–F NOE measurement. The expected fluoromethylene tosylpyrrolidine 2a was not detected. When a AuCl complex was used, product 3a was obtained in 46% yield with a new monofluorinated 2-pyrroline 5a in 7% yield (Table 1, entry 2). In the presence

• column chromatography. NMR spectra (1H, 13C, DEPT, COSY, HMQC, HMBC, NOE) were recorded at room temperature at 300 or 400 MHz on a Bruker AVANCE spectrometer. Chemical shifts are given in ppm, referenced to the residual proton resonance of the solvents (δ = 7.26 for CHCl3) or to the residual carbon

NMR studies of anion-induced conformational changes in diindolylureas and diindolylthioureas

• Damjan Makuc,
• Jennifer R. Hiscock,
• Mark E. Light,
• Philip A. Gale and
• Janez Plavec

Beilstein J. Org. Chem. 2011, 7, 1205–1214, doi:10.3762/bjoc.7.140

• mechanics calculations. NOE experiments showed that the anti–anti conformer along the C7–N7α bonds was predominant in DMSO-d6 solution in the absence of anions. Anion-induced changes in the 1H and 15N chemical shifts confirm the weak binding of chloride anions with negligible conformational changes. Strong

• make conformational studies even more appealing. The conformational characteristics of diindolylurea 1 were assessed by the use of 1D difference NOE experiments in the absence and in the presence of anions. The orientation along the C7–N7α bonds was established by comparative evaluation of NOE

• enhancements of H7α with H1 and H6 protons. The saturation of H7α in 1 gave strong NOE at H6 (10.4%) and moderate NOE at H1 (4.3%), which suggested that the anti orientation prevails along the linkage between ureido moiety and indole ring (Figure 4a). As the observed NOE enhancements are primarily a function

Long-range diastereoselectivity in Ugi reactions of 2-substituted dihydrobenzoxazepines

• Luca Banfi,
• Andrea Basso,
• Valentina Cerulli,
• Valeria Rocca and
• Renata Riva

Beilstein J. Org. Chem. 2011, 7, 976–979, doi:10.3762/bjoc.7.109

• the isocyanide derived substituent prefers an axial position in both stereoisomers, as demonstrated by NOE experiments carried out on 6e (Supporting Information File 2). Thus, after attack, the trans initial adduct 10 undergoes a conformational change to 11. The two vicinal J2-3 (i.e., 2.1 and 9.3 Hz

An efficient and practical entry to 2-amido-dienes and 3-amido-trienes from allenamides through stereoselective 1,3-hydrogen shifts

• Ryuji Hayashi,
• John B. Feltenberger,
• Andrew G. Lohse,
• Mary C. Walton and
• Richard P. Hsung

Beilstein J. Org. Chem. 2011, 7, 410–420, doi:10.3762/bjoc.7.53

• °C in a sealed tube, 1,3-hydrogen shift took place exclusively from the α-position affording highly substituted (E)-2-amido-dienes 33a and 34 in 71% and 79% yields, respectively (Table 4, entries 1 and 3). The E-geometry in 33a and 34 was assigned by NOE (Supporting Information File 2). Intriguingly

• information on synthesis, purification and characterization data of all substances given in this article, proton and selected carbon NMR spectra, and X-ray data of compound 10b. Supporting Information File 138: Experimental section. Supporting Information File 139: Proton and Carbon NMR spectra, and NOE data

Rh-Catalyzed rearrangement of vinylcyclopropane to 1,3-diene units attached to N-heterocycles

• Franca M. Cordero,
• Carolina Vurchio,
• Stefano Cicchi,
• Armin de Meijere and
• Alberto Brandi

Beilstein J. Org. Chem. 2011, 7, 298–303, doi:10.3762/bjoc.7.39

• basis of 1H NMR data. In particular, the diene 18 showed the typical signals of an exocyclic vinyl substituent (δ 7.00 (=CHv), 5.17 (=CHHcis), 5.17 (=CHHtrans) ppm; Jtrans = 17.5, Jcis = 11.3 Hz). Irradiation of 11b-H (δ 4.76 ppm) produced a positive NOE on the olefinic Htrans whereas irradiation of =CH

• ) gave enhancement of the ethylidene methyl group (δ 1.76 ppm), and irradiation of Hc (δ 5.29 ppm) showed enhancement at 11-H and 11b-H (δ 6.56 and 4.41 ppm). For the isomer (Z)-19, irradiation of Hc’ (δ 5.96 ppm) gave enhancement of Hb’ (δ 4.89 ppm) and an NOE interaction was present between the methyl

• based on nitrones and bicyclopropylidene. Key NOE interactions. 18: 11b-H/11-H, 11b-H/6-H, 11b-H/Ht, Hv/2-CH3; E-19: Hb/CH3, Hc/11b-H, Hc/11-H; Z-19: Hb’/Hc’, 11b-H/CH3. General approach to spirocyclopropanated tetrahydropyridones by 1,3-dipolar cycloaddition/thermal rearrangement. Synthesis of

Effects of anion complexation on the photoreactivity of bisureido- and bisthioureido-substituted dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 278–289, doi:10.3762/bjoc.7.37

• corresponding Job plot confirms the 1:1 complex between 1h and SMD (Supporting Information File 1). Moreover, complex formation was confirmed by a weak NOE effect, as determined by ROESY NMR experiments, between the protons in the ortho position of the phenyl group of the mandelate and the bis(trifluoro)phenyl

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• wherein all the observed interactions are in agreement with the structure (for HMBC see the Experimental). The exo-stereochemistry of the product was established from the NOESY spectrum where an NOE interaction between the H-7 and H-10, and the H-7 and H-15 were present (for the notation of atoms see the

• present, in accord with the proposed structures. However, from their spectra we were unable to assign the syn- or the anti-stereochemistry to the isolated products 7. In the NOESY spectra of both isolated compounds, an NOE interaction was observed between the H-atoms at the position 1 and 11 (for the

• ), calculated for C19H22NO2 296.1645, observed 296.1649. Important HMBC interactions: H-19 and C-6, C-2, C-9, C-10; H-17 and C-19; H-16 and C-14, C-20; H-15 and C-9; H-12 and C-19; H-10 and C-19, C-8; H-4 and C-2, C-8; H-6 and C-8; H-7 and C-9; Important NOE interactions: H-7 and H-15; H-17 and H-10. rel-(1R

Accuracy in determining interproton distances using Nuclear Overhauser Effect data from a flexible molecule

• Catharine R. Jones,
• Craig P. Butts and
• Jeremy N. Harvey

Beilstein J. Org. Chem. 2011, 7, 145–150, doi:10.3762/bjoc.7.20

• Catharine R. Jones Craig P. Butts Jeremy N. Harvey Department of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, United Kingdom 10.3762/bjoc.7.20 Abstract The determination of accurate NOE-derived interproton distances and confirmation/prediction of relative populations in

• multi-conformer, flexible small molecules was investigated with the model compound 4-propylaniline. The low accuracy assumed for semi-quantitative NOE distance restraints is typically taken to suggest that large numbers of constraints need to be used in the dynamical analysis of flexible molecules, and

• this requires, for example, the measurement and Karplus-type analysis of scalar coupling constants (3JCH and 3JHH). Herein we demonstrate that, contrary to this common perception, NOE measurements alone are accurate enough to establish interproton distances, and hence conformational detail, in flexible

Synthesis of cationic dibenzosemibullvalene-based phase-transfer catalysts by di-π-methane rearrangements of pyrrolinium-annelated dibenzobarrelene derivatives

• Heiko Ihmels and
• Jia Luo

Beilstein J. Org. Chem. 2011, 7, 119–126, doi:10.3762/bjoc.7.17

• : 4.17, 4.91; 3fI: 4.31, 5.05 ppm; 3fII: 4.20, 5.02, in CDCl3). After column chromatography and subsequent recrystallization, the major photoproducts 3eI and 3fI were isolated in low yields (15% and 18%). The relative configuration of the ammonium functionality was deduced from NOE experiments

• . Specifically, the close proximity between the methyl group and the methine proton (8b’-H) of the cyclopropane ring gave rise to an NOE in 3eI and 3fI (Scheme 3). The structure of the minor products 3eII and 3fII, although not isolated, were determined by 1H NMR spectroscopic analyses of the photolysates. In