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

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