Synthesis of constrained analogues of tryptophan

• Elisabetta Rossi,
• Valentina Pirovano,
• Marco Negrato,
• Giorgio Abbiati and
• Monica Dell’Acqua

Beilstein J. Org. Chem. 2015, 11, 1997–2006, doi:10.3762/bjoc.11.216

• reasonably assigned on the basis of NOE interactions between H-5 and the two H-4 hydrogens, Figure 3. Furthermore, for compound 3a it was possible to observe diagnostic NOE interactions between NH and the three cis hydrogens in position 1, 2 and 4, Figure 3. On the contrary, for compound 3'a in Figure 3, NH

• NOE interactions involve cis hydrogens at positions 1 and 4 and the aromatic p-tolyl hydrogens, Figure 3. Finally, tetrahydrocarbazoles 3a,b,d and 3'a were selected as substrates to test the reactivity of our compounds under hydrolytic conditions to obtain the deprotection of indole nitrogen and the

Investigation of the role of stereoelectronic effects in the conformation of piperidones by NMR spectroscopy and X-ray diffraction

• Cesar Garcias-Morales,
• David Ortegón-Reyna and
• Armando Ariza-Castolo

Beilstein J. Org. Chem. 2015, 11, 1973–1984, doi:10.3762/bjoc.11.213

• mass spectrometry. The H,H and H,C connectivities were determined by COSY and HSQC experiments, while the conformation was determined by nOe through t-ROESY experiments. Figure 5 shows the 1H NMR spectrum of 1. Three signals are present in the aliphatic region: H(2,4)ax protons as a double signal at δ

• through nOe (Figure 6a). In 4, nOe was observed among H(4)ax, H(5)eq, and H(2)ax, and for H(7)ax with H(6)eq and H(8)eq. Furthermore, nOe was observed among H(5)eq, H(6)ax, and H(6)eq (Figure 6b). Based on the nOe values and 3JH,H coupling constants, the solution conformation was determined using the

• decoupling experiment both with and without nOe at 125.76 MHz using a spectral width of 31446.54 Hz, an acquisition time of 0.8 s, 32678 points, 2052 scans, and a recycle delay of 0.1 s. The non-decoupled 13C NMR spectra with nOe were recorded with a spectral width of 39308.17 Hz, a resolution of 0.9 Hz, and

SmI₂-mediated dimerization of indolylbutenones and synthesis of the myxobacterial natural product indiacen B

• Nils Marsch,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2015, 11, 1700–1706, doi:10.3762/bjoc.11.184

• be too distant from each other to show an nOe. In any cyclopentane conformation this would be the case for hydrogen atoms located in 1,3-trans-position. Thus, the presence of a NOESY cross peak would exclude 1,3-trans-orientation of the respective hydrogens. In diastereomers 6, 7, and 8 there were

Towards inhibitors of glycosyltransferases: A novel approach to the synthesis of 3-acetamido-3-deoxy-D-psicofuranose derivatives

• Maroš Bella,
• Miroslav Koóš and
• Chun-Hung Lin

Beilstein J. Org. Chem. 2015, 11, 1547–1552, doi:10.3762/bjoc.11.170

• -psicofuranose (11) as the suitable substrate for thioglycosylation. Attempts to determine the configuration at the anomeric center in compounds 10 or 11 by employing NOE NMR technique were ambiguous. Although both derivatives 10 and 11 were crystalline solids, it was not possible to obtain suitable crystals for

Tandem cross enyne metathesis (CEYM)–intramolecular Diels–Alder reaction (IMDAR). An easy entry to linear bicyclic scaffolds

• Javier Miró,
• María Sánchez-Roselló,
• Álvaro Sanz,
• Fernando Rabasa,
• Carlos del Pozo and
• Santos Fustero

Beilstein J. Org. Chem. 2015, 11, 1486–1493, doi:10.3762/bjoc.11.161

• -exo. After chromatographic separation, NOESY experiments indicated that 10b-endo shows two nOe correlations: one between H1 and H2 (which indicates the cis-fusion of the two cycles) and another one between H1 and the aromatic proton H3. These two nOe interactions, together with the absence of a

• correlation between H1 and H4 indicated that the phenyl ring and H1 display a cis relationship. Additionally, compound 10b-exo only showed an nOe correlation between H1 and H3 (Figure 1). For the rest of compounds 10, an analogous stereochemical outcome was assumed. Conclusion In conclusion, a new tandem CEYM

Structure and conformational analysis of spiroketals from 6-O-methyl-9(E)-hydroxyiminoerythronolide A

• Ana Čikoš,
• Irena Ćaleta,
• Dinko Žiher,
• Mark B. Vine,
• Ivaylo J. Elenkov,
• Marko Dukši,
• Dubravka Gembarovski,
• Marina Ilijaš,
• Snježana Dragojević,
• Ivica Malnar and
• Sulejman Alihodžić

Beilstein J. Org. Chem. 2015, 11, 1447–1457, doi:10.3762/bjoc.11.157

• less stable nonanomeric form [23]. To determine the configuration at 9-C and elucidate the conformation of 2, nOe analysis was performed (Tables SI1 and SI2, in Supporting Information File 1), followed by molecular modelling. Very strong nOe correlations between 2-H, 5-H and 10-H observed in both DMSO

• -d6 and CDCl3 attest to their close spatial proximity (2.0–2.6 Å). Other characteristic observed nOe interactions are: very strong 4-H↔6-Me, 8-Me↔10-Me, 3-H↔4-Me, 5-H↔7-Hax, 5-H↔6-Me, 5-H↔10-Me correlations and a weak interaction between 4-Me and 5-H. To simplify the generation of the three

• 5C8 conformation which explains the observed system of nOe correlations between 2-H, 5-H and 10-Me (2.2–2.9 Å), as well as 8-Me↔10-Me (2.7 Å) and 11-H ↔14b-H (2.8 Å) interactions, all shown in Table SI3, in Supporting Information File 1. The coupling constants 3J8-H,7-Ha and 3J8-H,7-Hb (one strong

Novel carbocationic rearrangements of 1-styrylpropargyl alcohols

• Christine Basmadjian,
• Fan Zhang and
• Laurent Désaubry

Beilstein J. Org. Chem. 2015, 11, 1017–1022, doi:10.3762/bjoc.11.114

• could not detect any cyclopentenone. Instead, we were amazed to isolate the rearranged ketone 17 (entry 3, Table 1). Indeed, 4,4-diarylnaphthalen-1-ones are highly unusual compounds, whose synthesis is rarely described in literature [11]. The structure of 17 was confirmed by NOE and key HMBC

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• integration of the aromatic protons and benzylic protons to 15 and 4, respectively, indicate the abstraction of the H-2 and elimination of the benzyloxy group at C-3. The absence of a coupling between H-1 and H-5 in the NOE NMR spectrum confirmed the α-configuration of the glycosidic bond at C-1. The

Further exploration of the heterocyclic diversity accessible from the allylation chemistry of indigo

• Alireza Shakoori,
• John B. Bremner,
• Mohammed K. Abdel-Hamid,
• Anthony C. Willis,
• Rachada Haritakun and
• Paul A. Keller

Beilstein J. Org. Chem. 2015, 11, 481–492, doi:10.3762/bjoc.11.54

• structure about the 2,2’-double bond of these compounds was presumed to be transoid based on the retention of the intense blue colour which arises from the presence of at least one H-bond between the NH and carbonyl, as well as the absence of a nOe interaction between the N-methylene and the NH present

• cinnamyl methylene (H1''). Appearance of a multiplet at 2.98–3.10 ppm assigned to the C–CH2 revealed the 2.4 ppm shift compared to the chemical shift of deshielded O–CH2 protons in the spiro product. Another signal appearing at 7.87 ppm, assigned to an NH, and its nOe correlation with H7 from the aromatic

C-5’-Triazolyl-2’-oxa-3’-aza-4’a-carbanucleosides: Synthesis and biological evaluation

• Roberto Romeo,
• Caterina Carnovale,
• Salvatore V. Giofrè,
• Maria A. Chiacchio,
• Adriana Garozzo,
• Emanuele Amata,
• Giovanni Romeo and
• Ugo Chiacchio

Beilstein J. Org. Chem. 2015, 11, 328–334, doi:10.3762/bjoc.11.38

• , predominates. The structure of the obtained compounds was determined by spectroscopic data and MS analysis: the main product of the reaction was the cis derivative. NOE measurements confirm the assigned stereochemistry. For compound 11, the cis isomer, irradiation of the H-5 resonance at 5.99 ppm (as doublet

• of doublets) induced a positive NOE effect on H-3 resonance at 3.85–4.00 ppm (as a multiplet) and on H-4b proton (2.34–2.42 ppm, multiplet) (Scheme 1). Accordingly, in the trans derivative 12, on irradiating H-5 resonance (6.14 ppm; doublet of doublets), a positive NOE effect was detected only for

Visible-light-induced bromoetherification of alkenols for the synthesis of β-bromotetrahydrofurans and -tetrahydropyrans

• Run Lin,
• Hongnan Sun,
• Chao Yang,
• Youdong Yang,
• Xinxin Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2015, 11, 31–36, doi:10.3762/bjoc.11.5

• conditions. Moreover, the stereochemistry of the bromotetrahydrofurans compound 2a was misidentified before. Herein, the stereochemistry of the bromotetrahydrofurans compound 2a was determined by NOE spectra, for details see Supporting Information File 1. After a screening of selected solvents, we found

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• revealed interesting 1H NMR and NOESY data which are summarized in Figure 3 (A and B). A strong nOe between the protons 8-H and 1-H (A), 5-H and 8a-H, 1-H and 2-H as well as the absence of a nOe between 8a-H and 1-H led us to conclude that dihydroxylation has taken place from the α-face as expected. The 1H

• = 17.4, 4.8 Hz) protons as well as strong nOe between the protons on 6-H and 9a-H, 6-H and 8-H, 8-H and 9a-H, 1-H and 2-H and 2-H and 3-H as indicated in Figure 5. These studies led us to believe [38] the molecular conformation of 23 to be 5C8. Conclusion In conclusion, we have developed an efficient

• complement to those existing in the literature. The prepared compounds may also prove to be biologically important. Selected polyhydroxyindolizidine and quinolizidines of importance. Target bicyclic imino sugars Ia and Ib from a common intermediate IV. Selected nOe correlations (A) and coupling constants (B

Stereoselective synthesis of perillaldehyde-based chiral β-amino acid derivatives through conjugate addition of lithium amides

• Zsolt Szakonyi,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2014, 10, 2738–2742, doi:10.3762/bjoc.10.289

• determined by 2D NMR techniques. Remarkable nOe correlations were observed between C2-H and C9-Me (10A and 10D), between C1-H and C8-H (10A), and a weak effect was found between C1-H and C8-H (10B) (see Figure 1 for numbering). Amino esters 7A–D were transformed to the appropriate amino acids 10A–D in three

Preparation of neuroprotective condensed 1,4-benzoxazepines by regio- and diastereoselective domino Knoevenagel–[1,5]-hydride shift cyclization reaction

• László Tóth,
• Yan Fu,
• Hai Yan Zhang,
• Attila Mándi,
• Katalin E. Kövér,
• Tünde-Zita Illyés,
• Attila Kiss-Szikszai,
• Balázs Balogh,
• Tibor Kurtán,
• Sándor Antus and
• Péter Mátyus

Beilstein J. Org. Chem. 2014, 10, 2594–2602, doi:10.3762/bjoc.10.272

• same side of the molecules, the analysis of the computed solution conformers of cis-7a,b revealed that the orientation and distance (>4.6 Å) of these methine protons (Figure 3) does not allow for the detection of their NOE contact, rendering the NOE-based assignment of the relative configuration

• ambiguous. Similarly, no NOE correlation is expected between 2-H and 15a-H of trans-7a,b, which was also evident from the structures of their computed lowest-energy conformers (Figure 2). Accordingly, no characteristic NOE was observed between these methine protons for 7a,b, which did not help for the

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• spectrometry analysis and a mutual NOE between H18 and H20. The relative Z stereochemistry of tetrabromo derivative 7 was unambiguously established by X-ray analysis; however, there is a disordered carbon–bromine bond and the structure could not be completely refined. The ratio of 5 and 6 was determined as 1

New highlights of the syntheses of pyrrolo[1,2-a]quinoxalin-4-ones

• Emilian Georgescu,
• Alina Nicolescu,
• Florentina Georgescu,
• Florina Teodorescu,
• Daniela Marinescu,
• Ana-Maria Macsim and
• Calin Deleanu

Beilstein J. Org. Chem. 2014, 10, 2377–2387, doi:10.3762/bjoc.10.248

• allowing for the determination of chemical shifts, multiplicities, and coupling constants. For compounds 4h, 4i, 5b and 5e, the carbomethoxy respectively carbethoxy residues were assigned based on their NOE response. Thus, for compounds 4h,i the methyl protons from carbomethoxy groups situated in positions

• 2 and 3 were differentiated based on their NOE cross peak with the proton in position 1. For compounds 5b,e the protons from carbethoxy groups situated in positions 1 and 3 were assigned based on their NOE cross peaks with the proton in position 8, an example for 5b is shown in Figure 3. Based on

• the NOE assignments of various ethyl groups, we suppose that the preferred conformation in solution for the carbethoxy group in position 1 in compounds 5b,e,h is oriented towards the benzo-annelated nucleus, thus the aromatic ring current inducing a deshielding effect on the CH2 and CH3 groups. On the

Photochemical approach to functionalized benzobicyclo[3.2.1]octene structures via fused oxazoline derivatives from 4- and 5-(o-vinylstyryl)oxazoles

• Ivana Šagud,
• Simona Božić,
• Željko Marinić and
• Marija Šindler-Kulyk

Beilstein J. Org. Chem. 2014, 10, 2222–2229, doi:10.3762/bjoc.10.230

• 1740 and 1714 cm–1. No signal for a NH proton was found in the 1H NMR (Figure 2: (a)) nor the NH band in the IR spectrum. Its HRMS also confirmed the compound without the presence of nitrogen. The NOE interaction between protons HA and HG proved that the HA proton is facing to the methano bridge and

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds

• Miroslav Palík,
• Jozef Kožíšek,
• Peter Koóš and
• Tibor Gracza

Beilstein J. Org. Chem. 2014, 10, 2077–2086, doi:10.3762/bjoc.10.216

• arrangement of the substituents at C4/C7 in the product of the 6-endo-trig cyclisation was determined by means of 1H NMR and NOE interactions. In conclusion, we have also shown the possibility to construct interesting bicyclic intermediates in a 2 step sequence combining the PdII-catalysed cyclisation [36][37

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• provide NOE contacts to protons on both sides of the pyrrolidine ring, suggesting an exchange of deuterium connected to the pyrrolidine nitrogen. NMR study of phosphonoformyl derivatives In contrast to 7–10, an amidic pyrrolidine nitrogen atom in phosphonoformyl derivatives 11–14 is not involved in

Facile synthesis of 1-alkoxy-1H-benzo- and 7-azabenzotriazoles from peptide coupling agents, mechanistic studies, and synthetic applications

• Mahesh K. Lakshman,
• Manish K. Singh,
• Mukesh Kumar,
• Raghu Ram Chamala,
• Vijayender R. Yedulla,
• Domenick Wagner,
• Evan Leung,
• Lijia Yang,
• Asha Matin and
• Sadia Ahmad

Beilstein J. Org. Chem. 2014, 10, 1919–1932, doi:10.3762/bjoc.10.200

• moiety could be ascertained relative to the aromatic protons via NOE experiments (Scheme 4). Reaction of At-OTs with MeOH yielded a 1-methoxyazabenzotriazole (At-OMe), and the 1H NMR spectrum of the crude reaction mixture indicated the presence of only one product. Comparison of the 1H NMR data of the

• purified material to those reported [35] for 1-methoxy-1H-4-azabenzotriazole (1-methoxy-1H-[1,2,3]triazolo[4,5-b]pyridine) and 1-methoxy-1H-7-azabenzotriazole (3-methoxy-3H-[1,2,3]triazolo[4,5-b]pyridine) did not allow for ready identification. A NOE experiment did not result in observable interactions of

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• component of polyoxins A, F, H, and K, which exhibit antibiotic properties [72]. Originally, the stereochemistry of the exocyclic double bond of polyoximic acid was incorrectly assigned as E based on a low resolution nOe experiment (Figure 3). The total synthesis of polyoximic acid (9) by Hanessian and co

Sacrolide A, a new antimicrobial and cytotoxic oxylipin macrolide from the edible cyanobacterium Aphanothece sacrum

• Naoya Oku,
• Miyako Matsumoto,
• Kohsuke Yonejima,
• Keijiroh Tansei and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2014, 10, 1808–1816, doi:10.3762/bjoc.10.190

• as evidenced by one-to-one NOE correlations between the acetonide methyl groups and oxymethine protons. Therefore, it was concluded that C13 has an R-configuration. Sacrolide A (1) is apparently a member of the oxylipins, lipid oxidation products reported from all organisms, and its biosynthesis

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• , HMQC, gs-HSQC, gs-HMBC, COSY, TOCSY, NOESY and NOE-difference spectroscopy. In compounds 4–7 the trifluoromethyl group exhibits very consistent chemical shifts, ranging from δ(F) −60.8 to −61.9 ppm. The fluorine resonance is split into a doublet by a small coupling (0.5–0.9 Hz) due to a through-space

Concise total synthesis of two marine natural nucleosides: trachycladines A and B

• Haixin Ding,
• Wei Li,
• Zhizhong Ruan,
• Ruchun Yang,
• Zhijie Mao,
• Qiang Xiao and
• Jun Wu

Beilstein J. Org. Chem. 2014, 10, 1681–1685, doi:10.3762/bjoc.10.176

• cleavage of the 2-O-benzyl group at perbenzylated 1-O-methylribofuranose analogues. Dess–Martin oxidation of compound 9 provided ketone 10 in 92% yield. Next, the addition reaction with CH3MgBr in dry ether gave 11 exclusively with the requisite β-methyl configuration at C-2. NOE experiments showed correct

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• sequence, which incorporates a regioselective pyrrole alkylation, an electrophilic aromatic nitration and a regio- and stereoselective Corey–Noe–Lin dihydroxylation [18], has previously been described (in the total synthesis of heronapyrrole C) [3]. The procedure of Shi et al. [19][20][21] was then used to