Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• references [40][41]). The relative configuration of the newly formed stereogenic center at the C-2 position of 13 was successfully determined by NOE experiments. By irradiation of the 2-H proton (Figure 2) several dipolar couplings with 1-H, 4-H and with one proton of the p-bromophenyl group were observed

• (back-side) attack is probably hindered by the bulky OTBS group (also see Scheme 5). The configurational assignments are in accordance with NOE experiments performed with the alcohol derived from ketone 13 (precursor of 16), where dipolar couplings have been observed between the 10-H and 9-H protons

Synthesis of the B-seco limonoid core scaffold

• Hanna Bruss,
• Hannah Schuster,
• Rémi Martinez,
• Markus Kaiser,
• Andrey P. Antonchick and
• Herbert Waldmann

Beilstein J. Org. Chem. 2014, 10, 194–208, doi:10.3762/bjoc.10.15

• H9 and H11 and nOe signal enhancements. In contrast to the high face-selectivity in the rearrangement of the model systems, the reaction seems to take place from both sides of the bicyclic C–D system. However, in this case the si-face approach appears to be favoured (transition state C, Figure 3a

• regioselective opening [60][61] leading to the β-hydroxyketone that was temporarily masked as a TES ether. Reduction of ketone 85 with NaBH4 resulted in the formation of two diastereomeric alcohols in 2:1 ratio. To our delight flash chromatography permitted smooth separation of the two compounds. nOe studies

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

• Tatyana L. Pavlovskaya,
• Fedor G. Yaremenko,
• Victoria V. Lipson,
• Svetlana V. Shishkina,
• Oleg V. Shishkin,
• Vladimir I. Musatov and
• Alexander S. Karpenko

Beilstein J. Org. Chem. 2014, 10, 117–126, doi:10.3762/bjoc.10.8

• obtained by the above method were characterized by mass spectrometry, 1H and 13C NMR, and elemental analyses. The regiochemical outcome of the cycloaddition was unambiguously confirmed by NOE experiments in 1H NMR as well as later by a single crystal X-ray structure analysis of the cycloadduct 4a. The 1H

• NMR spectra of compounds 4b–4d have two multiplets at 4.07–3.72 ppm for 7a’-CH and 3.50–3.35 ppm for 2’-CH (compound 4b) or 6’-CH (compound 4d) and a singlet at 1.45 ppm for 2’-CCH3 of compound 4c. The relative stereochemistry of compounds 4b–4d was established by NOE cross peaks between 7a’-CH and 2

• ’(6’-CH) and 2’-CCH3. Also, multiplets for 7a’-CH and 2’-(6’-CH) and singlet for 2’-CCH3 show correlation signals to the neighboring methylene groups. Additionally, the absence of the NOE cross peak of 4-CH of the isatin nucleus and 2’(6’-CH) or 2’-CCH3 of the pyrrolizidine moiety was indicative for

Plakilactones G and H from a marine sponge. Stereochemical determination of highly flexible systems by quantitative NMR-derived interproton distances combined with quantum mechanical calculations of ¹³C chemical shifts

• Simone Di Micco,
• Angela Zampella,
• Maria Valeria D’Auria,
• Carmen Festa,
• Simona De Marino,
• Raffaele Riccio,
• Craig P. Butts and
• Giuseppe Bifulco

Beilstein J. Org. Chem. 2013, 9, 2940–2949, doi:10.3762/bjoc.9.331

• sponge Plakinastrella mamillaris collected at Fiji Islands, is reported. The stereostructural studies began on plakilactone H by applying an integrated approach of the NOE-based protocol and quantum mechanical calculations of 13C chemical shifts. In particular, plakilactone H was used as a template to

• between plakilactone G and plakilactone H allowed us to determine the absolute configuration in this two new oxygenated polyketides. Keywords: chemical shift calculations; DFT; NMR spectroscopy; quantitative NOE; stereochemical determination of flexible systems; Introduction In recent years the quantum

• relative configuration assignment based on experimental interproton distances derived from a quantitative and accurate NOEs analysis [18]. These quantitatively measured NOEs have been initially developed for the stereochemical assignments of rigid molecular frameworks, as the NOE analysis is complicated

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

• I. Wayan Mudianta,
• Victoria L. Challinor,
• Anne E. Winters,
• Karen L. Cheney,
• James J. De Voss and
• Mary J. Garson

Beilstein J. Org. Chem. 2013, 9, 2925–2933, doi:10.3762/bjoc.9.329

• -11 based on HMBC correlations from the alkene proton H-10 (δH 5.07) to CH3-12 and C-8. The C-6/C-7 configuration was revealed as Z rather than the E-configuration anticipated, based on 1D nOe experiments in which the signal intensity of H3-14 increased when the signal attributed to H-6 was irradiated

• (mixing time 60 ms). 1D nOe irradiation of H-10 provided assignment of the signals corresponding to CH3-12. Total synthesis of (−)-(5R,6Z)-dendrolasin-5-acetate (1) In view of the small sample (0.1 mg) of natural material available, a synthetic study was undertaken to provide stereochemical

• mixture of 7a/b was the sole [1,2]-Wittig rearrangement product obtained. Racemic 5-hydroxydendrolasin (7a/b) was next subjected to HPLC (hexanes/EtOAc, 90:10) to provide the individual E- (7a) and Z-isomers (7b) that were each carefully characterised by 1H NMR and 1D nOe experiments. Assignment of the

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

• Silke Felix,
• Louis P. Sandjo,
• Till Opatz and
• Gerhard Erkel

Beilstein J. Org. Chem. 2013, 9, 2866–2876, doi:10.3762/bjoc.9.323

• chain (δ 173.5). The relative configuration was deduced from NOESY data. Thus, protons of a methyl group at δ 1.04 showed NOE correlations with those of one of the geminal methyl groups (δ 1.15) and one of the oxymethylene protons (δ 4.48) of the lactone ring (Figure 3). Besides, the protons of the

The myxocoumarins A and B from Stigmatella aurantiaca strain MYX-030

• Tobias A. M. Gulder,
• Snežana Neff,
• Traugott Schüz,
• Tammo Winkler,
• René Gees and
• Bettina Böhlendorf

Beilstein J. Org. Chem. 2013, 9, 2579–2585, doi:10.3762/bjoc.9.293

• natural product. To unambiguously prove the substitution pattern at the aromatic ring system, the phenolic OH-group was selectively methylated using diazomethane. The resulting methyl ether was irradiated in a 1D NOE experiment, which resulted in the expected strong increase of the proton bound to C-6

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• NOE-correlation for H-18 and H-22 protons in the NOESY spectrum of 4 (see Supporting Information File 2). In the case of the ketone with the TES-protected benzylic alcohol, exposure to 2 N HCl in THF resulted in formation of numerous products, including the spiroketal 4, thus demanding further

Synthetic scope and DFT analysis of the chiral binap–gold(I) complex-catalyzed 1,3-dipolar cycloaddition of azlactones with alkenes

• María Martín-Rodríguez,
• Luis M. Castelló,
• Carmen Nájera,
• José M. Sansano,
• Olatz Larrañaga,
• Abel de Cózar and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2013, 9, 2422–2433, doi:10.3762/bjoc.9.280

• as base and toluene as solvent at 120 °C. Polycyclic compound 15 was finally obtained in 50% yield as single diastereoisomer (Scheme 8). Despite being a solid product it was not possible to perform an X-ray diffraction analysis. Positive (CH derived from NPM with the CH derived from NMM) nOe

Stereoselective synthesis of the C79–C97 fragment of symbiodinolide

• Hiroyoshi Takamura,
• Takayuki Fujiwara,
• Isao Kadota and
• Daisuke Uemura

Beilstein J. Org. Chem. 2013, 9, 1931–1935, doi:10.3762/bjoc.9.228

• protecting groups and subsequent stereoselective spiroacetalization were performed in one-pot with CSA in MeOH to provide spiroacetal 19 as a single stereoisomer [19][20]. The stereochemistry of 19 was elucidated by the observed NOE correlations between H-83 and H-91 as indicated by an arrow. The plausible

Structure elucidation of β-cyclodextrin–xylazine complex by a combination of quantitative ¹H–¹H ROESY and molecular dynamics studies

• Syed Mashhood Ali,
• Kehkeshan Fatma and
• Snehal Dhokale

Beilstein J. Org. Chem. 2013, 9, 1917–1924, doi:10.3762/bjoc.9.226

• , although only time-averaged structural information can be extracted in NMR time scale. Nuclear Overhauser Enhancement (NOE) experiments, which depend on internuclear distances, are used to identify the part of guest that is involved in complexation and to determine the position of the guest inside the CD

• of ROESY data. Macura and coworkers [25] and others [26] have shown that employing relative rather than absolute NOE intensities from within a given experiment can be used to calculate internuclear distances and vice versa with high accuracy using following equation, where I1 and I2 are intensities

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• product 4e in 52% yield according to initial E-configured 1e. The structure of compound 4e was determined by 1H NMR NOE spectra. The reaction was still operable with 1f, bearing a 1,2-disubsituted allene, giving the desired 4f in moderate yield (49%). Its E-configuration was determined by NOE measurements

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• the corresponding imidazolidine-2-thione formed by treatment with thiophosgene to give 22 (Scheme 5). In one dimensional nOe studies irradiation of the CHNH peak (δ 3.70, 1H, dd, J = 8.4, 5.4 Hz) caused a 3.65% enhancement of the CHN peak (δ 4.31, 1H, dt, J = 7.9, 5.9 Hz), indicating a cis-relative

• of resonance which would result in the formation of the E iPr group and the planar amide group during formation of 23. Reduction of the double bond with hydrogen over palladium on charcoal gave a single diastereoisomer 25 in quantitative yield. In one dimensional nOe studies irradiation of H-3 (δ

• nOe data tentatively suggested that protons H-3, H-5 and H-6 were all on the same face of the molecule. Deprotection of the PMP group with CAN gave compound 2. Extensive NMR (COSY, HMBC and NOESY) and analytical data were consistent with the structure drawn (2), but the 1H and 13C NMR did not match

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• alkene geometry was determined to be (2E,5E,8E) by measurement of NOE enhancements [4]. Ripostatin B and its C15 epimer can be obtained from ripostatin A by reduction with sodium borohydride, while ripostatin C can be formed from ripostatin A by a mild base-mediated elimination. Consequently, ripostatin

Dipolar addition to cyclic vinyl sulfones leading to dual conformation tricycles

• Steven S. Y. Wong,
• Michael G. Brant,
• Christopher Barr,
• Allen G. Oliver and
• Jeremy E. Wulff

Beilstein J. Org. Chem. 2013, 9, 1419–1425, doi:10.3762/bjoc.9.159

• several lines of evidence (including nOe information from the NMR studies, construction of likely molecular models, and comparison with known fluxional behavior for related structures [37]) strongly suggested that these differences could best be explained by the tricycle “breathing” through stereochemical

• /mol). The calculated structure of the lower-energy exo conformer was similar to the solid-state structure shown in Figure 1, and was consistent with the nOe and NMR shielding data discussed above. Seeking further evidence linking the calculated exo and endo structures to the observed major and minor

Substituent effect on the energy barrier for σ-bond formation from π-single-bonded species, singlet 2,2-dialkoxycyclopentane-1,3-diyls

• Jianhuai Ye,
• Yoshihisa Fujiwara and
• Manabu Abe

Beilstein J. Org. Chem. 2013, 9, 925–933, doi:10.3762/bjoc.9.106

• crystallographic analysis as well as by NOE measurements. The steady-state photolyses of AZc–g in benzene solution were performed with a Xenon lamp (500 W) through a Pyrex filter (hν > 300 nm). The ring-closed compounds CPc–g were quantitatively obtained in the denitrogenation reaction (Scheme 2). The quantum

• purified by column chromatograph to give the product as colorless liquid (ca. 60%). The endo configuration was determined by NOE measurements. endo-2,3-Diazo-10,10-dibenzyloxy-1,4-diphenyltricyclo[5.2.1.05,9]dec-2-ene (AZc). IR (neat, cm−1): 3037, 2968, 2886, 1739, 1607, 1498, 1456, 1387, 1139, 1085, 1029

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• and β-CD was proven by 1H NMR rotating-frame Overhauser effect spectroscopy (ROESY) (Figure 1). NOE correlation signals of the β-CD cavity protons between 4 and 3.5 ppm and the aromatic protons of the pyridine moiety 8.6–7.4 ppm were observed, clearly proving the formation of complexes. However, no

• NOE interaction between protons of the methyl group of the thiazole and the triazole proton itself with CD is noticed. This indicates that only the inclusion of the pyridine moiety in the hydrophobic cavity of the CD takes place. The formation of supramolecular structures was also proven by UV–vis

Regio- and stereoselective carbometallation reactions of N-alkynylamides and sulfonamides

• Yury Minko,
• Morgane Pasco,
• Helena Chechik and
• Ilan Marek

Beilstein J. Org. Chem. 2013, 9, 526–532, doi:10.3762/bjoc.9.57

• by NOE (nuclear Overhauser effect) between the methyl substituent and the corresponding vinylic proton (E = H, Table 2, entry 4). However, such selectivity can only be achieved in nonpolar solvent, such as Et2O, since the same reaction performed in THF leads mainly to the formation of the β-isomer in

Zanthoxoaporphines A–C: Three new larvicidal dibenzo[de,g]quinolin-7-one alkaloids from Zanthoxylum paracanthum (Rutaceae)

• Fidelis N. Samita,
• Louis P. Sandjo,
• Isaiah O. Ndiege,
• Ahmed Hassanali and
• Wilber Lwande

Beilstein J. Org. Chem. 2013, 9, 447–452, doi:10.3762/bjoc.9.47

• 8.18 were further observed; the remaining signal was attributed to a methoxy group at δ 3.98 located at C-10 since its proton had a NOE contact (Figure 2) with the hydrogen at δ 8.18. The complete assignment was achieved by using HMBC data (Figure 2), which revealed correlations between H-4 at δ 7.86

• methylene extract of stem bark of Z. paracanthum. COSY, HMBC and NOE correlations of compounds 2, 3 and 4. Lethal concentration 50 (μg/mL) of extract A, B, C, and D after 24, 48 and 72 h. NMR data of compounds 2, 3 and 4 in CDCl3. Lethal concentration 50 (μg/ml) of compounds 1 and 2 after 24, 48 and 72 h

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

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