Stereocontrolled synthesis of 5-azaspiro[2.3]hexane derivatives as conformationally “frozen” analogues of L-glutamic acid

• Beatrice Bechi,
• David Amantini,
• Cristina Tintori,
• Maurizio Botta and
• Romano di Fabio

Beilstein J. Org. Chem. 2014, 10, 1114–1120, doi:10.3762/bjoc.10.110

• intermediate 16. The two most abundant diastereoisomers were isolated in pure form by semi-preparative chiral HPLC and their stereochemistry was elucidated by NOE studies [40]. In principle, as shown in Figure 2, the attack of the carbene intermediate to the olefin moiety 18 can occur at both the re and si

• -azaspiro[2.3]hexane. Relative energy values (kcal/mol) of the four diastereoisomer 20a–d calculated by the HF/631G* method. Supporting Information Experimental section comprising the synthesis of all newly synthesized compounds and intermediates, NOE studies and HPLC analysis on compounds 20a and 20c

• , Gaussian input files for QM calculations for compounds 20a, 20b, 20c and 20d, and copies of 1H and 13C NMR spectra for all new compounds. Supporting Information File 257: Experimental section. Supporting Information File 258: NOe studies and HPLC analysis on compounds 20a and 20c. Supporting Information

Cuevaenes C–E: Three new triene carboxylic derivatives from Streptomyces sp. LZ35ΔgdmAI

• Jing-Jing Deng,
• Chun-Hua Lu,
• Yao-Yao Li,
• Shan-Ren Li and
• Yue-Mao Shen

Beilstein J. Org. Chem. 2014, 10, 858–862, doi:10.3762/bjoc.10.82

• constitution of 1. The relative configuration of 3 was determined by the proton coupling constants and NOE correlations observed in NOESY experiments. The geometrical configuration of the triene side chain moiety in 3 was established to be 2E, 4E, and 6E by the proton spin coupling constant between 2-H and 3-H

• (J = 15.4 Hz) and the strong NOE correlations from 3-H to 6a-H3, 7-H and19-H, and from 4a-H3 to 5-H. Two conformations were observed in the NOE spectrum of 3 due to the rotation around the C-5/C-6 single bond (Figure 2). Therefore, compound 3 was determined to be the geometrical isomer of 1

• constitution of 4 and 5 were determined to be the amides of 1 and 3, respectively. The geometrical configuration of the triene side chain of 4 was established to be 2E, 4Z, and 6E by the proton spin coupling constant between 2-H and 3-H (J = 15.2 Hz) and the strong NOE correlations from 3-H to 5-H and from 4a

Use of activated enol ethers in the synthesis of pyrazoles: reactions with hydrazine and a study of pyrazole tautomerism

• Denisa Tarabová,
• Stanislava Šoralová,
• Martin Breza,
• Marek Fronc,
• Wolfgang Holzer and
• Viktor Milata

Beilstein J. Org. Chem. 2014, 10, 752–760, doi:10.3762/bjoc.10.70

• -carbonitrile (δ C3 139.8 ppm, δ C4 72.1 ppm, δ C5 151.4 ppm). Thus, it can be assumed that isomer 5aA2 provides a marked contribution to the tautomeric mixture. However, NOE measurement between the pyrazole-CH and pyrazole NH hints at the simultaneous presence of species 5aA1, where the protons involved are

Conformation of dehydropentapeptides containing four achiral amino acid residues – controlling the role of L-valine

• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Maciej Makowski,
• Rafał Latajka and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 660–666, doi:10.3762/bjoc.10.58

• based on the NOEs effects [33]. Characteristically strong NOE signals between the alpha proton from i and the amide proton from the consecutive i+1 residues indicate the type II β-turn [34]. This type of secondary structure is also confirmed by weak NOE signals from interactions between the amide

• determination of the preferred conformation. The reason for this may be the simultaneous coexistence of two types of conformations in solution – we observed NOE signals from both of them. In the case of peptide 3, structural calculations based on a much smaller number of structural constraints led to only one

• well-defined conformation. As shown in Figure 4 peptide 3 has a helical conformation. Both α- and 310-helix give a similar vicinity of the backbone protons of nonconsecutive residues between Hαi–HNi+2 and Hαi–HNi+3 [35]. Inai and Hirabayashi showed that the presence of NOE signals between Hαi–HNi+4

An oxidative amidation and heterocyclization approach for the synthesis of β-carbolines and dihydroeudistomin Y

• Suresh Babu Meruva,
• Akula Raghunadh,
• Raghavendra Rao Kamaraju,
• U. K. Syam Kumar and
• P. K. Dubey

Beilstein J. Org. Chem. 2014, 10, 471–480, doi:10.3762/bjoc.10.45

• , whereas the OH proton in 8a shows a high nOe (Scheme 6). Dihydro-β-carboline 7 was then subjected to an aromatization reaction to obtain eudistomin Y (6). The aromatization reaction was attempted with oxidizing agents such as DDQ and MnO2 as per the reported conditions in literature. The formation of

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• 44%, demonstrating the scalability and high practicability of our sequence. The relative configurations of compounds 9 and 11 were proven by NOE spectroscopy of piperidinols cis-11a–d, trans-11a, cis- and trans-16c, L-733,060.HCl and of oxazolidinones trans-10a and trans-10c (see Supporting

Efficient carbon-Ferrier rearrangement on glycals mediated by ceric ammonium nitrate: Application to the synthesis of 2-deoxy-2-amino-C-glycoside

• Alafia A. Ansari,
• Y. Suman Reddy and
• Yashwant D. Vankar

Beilstein J. Org. Chem. 2014, 10, 300–306, doi:10.3762/bjoc.10.27

• compound 12 was determined with the help of 1H NMR, COSY, nOe and decoupling experiments (Figure 1). Thus, the irradiation of the signal at δ 3.93 corresponding to H-3 led to an enhancement of the H-5 signal at δ 4.25 by 2.5%, while the peak at δ 4.63, corresponding to H-1, was not enhanced. This implies

• rearrangement of glycals by using ceric ammonium nitrate and several carbon nucleophiles. We have successfully employed the obtained C-allyl glycoside 2a for the stereoselective synthesis of a orthogonally protected 2-deoxy-2-amino-C-glycoside 12 via an Overman rearrangement as a key step. nOe and decoupling

Decandrinin, an unprecedented C₉-spiro-fused 7,8-seco-ent-abietane from the Godavari mangrove Ceriops decandra

• Hui Wang,
• Min-Yi Li,
• Félix Zongwe Katele,
• Tirumani Satyanandamurty,
• Jun Wu and
• Gerhard Bringmann

Beilstein J. Org. Chem. 2014, 10, 276–281, doi:10.3762/bjoc.10.23

• carbonyl carbon (δC 170.9) of a δ-lactone suggested its location at C-7, while those from H2-11, H-14, and H3-20 to the quaternary carbon (δC 88.3) placed it at C-9 (Figure 2). The NOE interactions for the two methyl groups at C-4 suggested that one methyl group is located at the same side as H-5, while

• experimentally were done with SpecDis 1.61 [41]. Structure of decandrinin (1). Selected 1H–1H COSY and HMBC correlations for decandrinin (1). Diagnostic NOE interactions for decandrinin (1, B97D/TZVP-optimized structure): arbitrarily the 5R,9R,10S-enantiomer is shown. Determination of the absolute configuration

• decandrinin (1), NOE interactions for the B97D/TZVP-optimized structure diagnostic for the 9-epimer of decandrinin (1), and comparison of the calculated ORD with the experimental one. Acknowledgements This work was financially supported by NSFC (31100258, 31170331, and 81125022), the Guangdong Key Science

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