Synthesis of a [6]rotaxane with singly threaded γ-cyclodextrins as a single stereoisomer

• Jason Yin Hei Man and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2019, 15, 1829–1837, doi:10.3762/bjoc.15.177

• . The 1H spectrum of 6R contains one set of sharp signals, suggesting that the [6]rotaxane is adopting a relatively rigid and symmetrical structure in solution (Figure 2a). NOE cross peaks between the triazole and CB[6] protons, and also Ha of the anthracene stoppers and CB[6] protons were observed

• , suggesting that the two CB[6] are interlocking at the triazole which is consistent with the strong binding of the CB[6] to the ammoniums (Figure S18 in Supporting Information File 1). Due to the severe peak overlapping in the aliphatic region at 3.5–4.5 ppm, NOE cross peaks in that regions cannot be

• elucidating the origin of the stereoselectivity in the synthesis of 6R. The 1H spectrum of 4R is generally similar to that of 6R and strong NOE cross peaks between the triazole and CB[6], and also Ha of the anthracene and CB[6] protons were observed (Figure S10 in Supporting Information File 1), confirming

The cyclopropylcarbinyl route to γ-silyl carbocations

• Xavier Creary

Beilstein J. Org. Chem. 2019, 15, 1769–1780, doi:10.3762/bjoc.15.170

• and 18. Additionally, nOe studies on 17 confirm the stereochemical assignment. Conversion to mesylates 19 and 20 using mesyl chloride and triethylamine was straightforward. Mesylate 19 reacts readily in CD3CO2D at 20 °C (Table 1) to give the substituted cyclobutyl acetate 21 (92%) as the major product

• borohydride reduction of the ester functionality of 63 gave a separable mixture of alcohols 64 and 65. The stereochemistry of the product 65 was established using nOe studies. Cyano to carbomethoxy conversion in 65 to give alcohol 66 was straightforward. Triflate derivatives 67 and 68 were prepared since

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• GalNAc and a carbonyl oxygen in the peptide main chain [33]. These conclusions had been based on the intensity of the observed NOE signals between main chain amide protons and α-protons. They conclude that the presence of strong NOE signals between Hαi and HNi+I protons (dHαi−HNi+1) together with the

• weak one between HNi and HNi+I protons (dHNi-HNi+1) or similar intensity of NOE signals between Hαi and HNi (dHα−HN1) as well as HNi+I (dHαi−HNi+1) is a sufficient evidence for the presence of the extended structure. However, a similar analysis of the determined NOE interactions did not provide enough

• peptide 3 (see Table 3 and Figure 4). Such situation is the result of numerous well defined intra- and interresidual NOE signals of sugar moiety protons (see Table S6, Supporting Information File 1). Although the orientation of the galactose ring is highly ordered, as shown the value of the temperature

Genomics-inspired discovery of massiliachelin, an agrochelin epimer from Massilia sp. NR 4-1

• Jan Diettrich,
• Hirokazu Kage and
• Markus Nett

Beilstein J. Org. Chem. 2019, 15, 1298–1303, doi:10.3762/bjoc.15.128

• spectrum of 1. Cañedo and co-workers had previously reported a (14R,15S,17R,19S) relative configuration for 2 [18]. As opposed to the NMR analysis of 2, we detected only a weak NOE correlation between H-14 and H-15. Furthermore, strong NOEs were observed from the N-methyl protons (H3-18) to both, H-17 and

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• allows to correlate the exchanging signals in both slow and fast exchange regimes. The measured ROESY spectrum featured both NOE interactions of the opposite phase and EXSY peaks of the same phase as diagonal peaks. The EXSY cross-peaks indicate the chemical exchange between methylene protons (H4), the

• aromatic protons (H1) and methyl protons (H6, Figure 4). The NOE interaction between the glycoluril methine protons (H5) and aromatic proton (H1, Figure 4) also confirmed the assignment of 1a-1. The integration of signals in 1H NMR spectra at −40 °C revealed uneven populations of conformers in a 4:3 ratio

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• imines 99 to furnish complex spirocyclic γ-lactams 101 (Scheme 29) [107]. These products show a trans orientation of the benzene moiety in the isoindolinone and the substituent in R2, according to NOE experiments and crystal structure analysis. The proposed mechanism involves an initial palladium

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• -oriented. Besides, the trisubstituted olefin (Δ3/15) was determined to be in E configuration due to the clear NOE correlations of H-15 with H3-13 and H3-14. In view of the above evidences, the relative configuration of compound 1 was determined as 1R*,2R*, the same as 1a [16][17]. Compound 2 was isolated

• ], was established by HR-ESIMS ion peaks at m/z 370.9654, [M − H]− (calcd for C15H17OBr2, 370.9646). The 1H and 13C NMR data of 4 were identical to those of 4a, a C-10 bromonated analogue of 3a. In addition, the NOE correlations between H3-13 (δH 1.21, s) with H-2 (δH 3.34, q, J = 7.3 Hz) and H-5a (δH

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• -hydroxy esters 9, 10 and 11 (dr = 1.74:0:38:0.24) in a total yield of 84% (Scheme 2). Gratifyingly, the percentage of derivatives 9 and 10 that show the desired stereochemistry at carbon center 5a is around 90%. The structure of all these isomers was confirmed by NOE experiments (see Supporting

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• moiety had clear correlations with the double bond carbons (δc 132.8, s, αC and δc 123.3, d, βC), and the βH exhibited clear HMBC correlations with the αC and carbonyl carbon (δc 168.8, s, CO). These NMR data clearly indicate the presence of a dhThr moiety (Figure 3), and the strong NOE between the γCH3

• amino acid sequence of cichorinotoxin; the NOESY data are shown in Figures S10A–S10F (Supporting Information File 1), and the HMBC data are shown in Figures S12A–S12C. Figures S10B and S10C highlight the NOE correlations of αNiH/αNi+1H. Figures S10D and S10E mainly depict the NOE correlations of αNiH

• , COSY and NOESY spectra of the tetraacetate are shown in Figures S13E–S13N (Supporting Information File 1). The NOE data indicated that the amino acid sequence of the tetraacetate is as shown in Figure S14 (Supporting Information File 1). The positions of the acetates were determined mainly from the

Ruthenium-based olefin metathesis catalysts with monodentate unsymmetrical NHC ligands

• Veronica Paradiso,
• Chiara Costabile and
• Fabia Grisi

Beilstein J. Org. Chem. 2018, 14, 3122–3149, doi:10.3762/bjoc.14.292

• , one of the N-aryl substituents was replaced with the smaller methyl group. Complex 164 was obtained in poor yield (30%) and characterized through NOE and X-ray analysis, revealing the exclusive formation of the rotational isomer in which the N-methyl lies over the carbene unit (the syn isomer, Figure

• case of 172, the Hoveyda-type analogue of 164 (Figure 32), for which a room temperature interconversion between syn and anti rotamers, observed at a ratio of 7.8:1, was revealed by NOE experiments. Surprisingly, despite such rotation the reactivity profiles and the enantioselectivities observed for 164

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• reaction described in this work occurred with high atom efficiency (atom economy of 90%) and produced only stoichiometric H2O as waste (E-factor of 0.1). Stereochemistry and mechanism The stereochemistries of 5a–m were ascribed by NOE NMR experiments. By example using 5a depicted in Figure 2, the 1H NMR

• spectrum showed that H(1) appears at 5.95 ppm as a singlet and H(4) at 4.72 ppm as a quadruplet. No distinct NOE effect was observed between H(1) and H(4), when either H(1) or H(4) was irradiated. A significant positive NOE effect was observed between H(1) and H(20). Thus, NOE analysis assumed that H(1) is

• between H(1) and H(4) in the NOE experiment. The structure contains two carbonyl moieties C(6)–O(2) and C(3)–O(1) with similar distances of 1.222 and 1.218 Å, respectively. The intramolecular hydrogen bond O(1)–H(13) remains strong in the nitrogenated tricycle (2.579 Å) vis-à-vis of the starting hydrazide

Synthesis of a water-soluble 2,2′-biphen[4]arene and its efficient complexation and sensitive fluorescence enhancement towards palmatine and berberine

• Xiayang Huang,
• Xinghua Zhang,
• Tianxin Qian,
• Junwei Ma,
• Lei Cui and
• Chunju Li

Beilstein J. Org. Chem. 2018, 14, 2236–2241, doi:10.3762/bjoc.14.198

• . For example, in the 2D NOESY spectra of host–guest mixture of 2,2’-CBP4 and B, NOE correlations were clearly observed between the middle protons H1 and H10 of B with the methylene Hc of 2,2’-CBP4, and between the aromatic protons (Hb) of 2,2’-CBP4 and H2 of B (Supporting Information File 1, Figure S11

A switchable [2]rotaxane with two active alkenyl groups

• Xiu-Li Zheng,
• Rong-Rong Tao,
• Rui-Rui Gu,
• Wen-Zhi Wang and
• Da-Hui Qu

Beilstein J. Org. Chem. 2018, 14, 2074–2081, doi:10.3762/bjoc.14.181

• ), H11 (peak C) (around the DBA recognition site) and methylene protons on the functional crown ether indicate that the DB24C8 macrocycle was located on the DBA site, corresponding to the structure of [2]rotaxane R1. After addition of 2 equiv DBU to the solution of R1, the NOE correlations between the

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• interactions are preserved under the MS conditions. Inclusion of the triazole in the CB[6] cavity was evidenced by the upfield shifted triazole resonance from 8.5 ppm to 6.4 ppm when compared with that of free triazole in non-interlocked system [22][24][25]. NOE cross peaks between the triazole and CB[6

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• -substituted phenol 126 to tricyclic spiroketals 127a,b in 56% yield using PIDA (15) as electrophilic species in acetonitrile at room temperature (Scheme 47). The mixture of both isomers was separated by flash column chromatography and the stereochemistry of major isomer 127a was assigned on the basis of NOE

Synthesis of diamido-bridged bis-pillar[5]arenes and tris-pillar[5]arenes for construction of unique [1]rotaxanes and bis-[1]rotaxanes

• Ying Han,
• Li-Ming Xu,
• Cui-Yun Nie,
• Shuo Jiang,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2018, 14, 1660–1667, doi:10.3762/bjoc.14.142

• cavity of one molecular pillar[5]arene, while another pillar[5]arene as the bigger stopper. Additionally, 2D NOESY spectra of the compound 5d provided more strong evidence for the formation of [1]rotaxane (Figure 3). The NOE correlations were clearly observed between Ha, Hb, Hc, Hd, and He protons of the

• be seen that the NOE correlations were clearly observed between Ha, Hb, Hc, Hd, Hf, Hg, Hh protons of the bridging diaminohexylene chain and the protons Hi, Hj in the core of pillar[5]arene. Additionally, some correlations exists between protons Ha, He, Hd and Hh and active amino (N–H) group. These

• NOE correlations clearly indicated the two bridged diaminohexylene chain threading into the cavity of the two pillar[5]arenes to form the bis-[1]rotaxane. The similar correlations were also observed in the NOESY spectra of the tris-pillar[5]arene 9b and 9c (see Supporting Information File 1, Figures

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• their macrolactone ring was assigned based on NOE and vicinal 1H NMR coupling constants and by calculation of a 3D model. Lanyamycin inhibited HCV infection into mammalian liver cells with an IC50 value of 11.8 µM, and exhibited a moderate cytotoxic activity against the mouse fibroblast cell line L929

• , i.e., 0.57 ppm, for C-43*. This allowed to observe a strong NOE between C-43 and 25OH, while the NOE between C-43* and 25*OH was only weak. Similarly, only the aromatic 35*/31* proton signals had an NOE with H-24* while the corresponding correlation was absent in isomer 1. Thus, the high-field shift

• = 9.5 Hz and J14/15 = 8 Hz indicated the trans orientation of their protons in the macrolactone ring with torsion angles of 177° and 170°. Further, the distances between proton pairs showing NOE interactions in the ROESY spectra of 1/2 were analyzed (Table 2). These distances showed a very good relation

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• ). This has been attributed to strong self-association (dimerization) in an antiparallel, head-to-tail orientation in aqueous solution during complex formation with duplex DNA oligomers verified via NOE experiments [61]. They further reported several structurally diverse MGBs, derived from distamycin, in

Cross-coupling of dissimilar ketone enolates via enolonium species to afford non-symmetrical 1,4-diketones

• Keshaba N. Parida,
• Gulab K. Pathe,
• Shimon Maksymenko and
• Alex M. Szpilman

Beilstein J. Org. Chem. 2018, 14, 992–997, doi:10.3762/bjoc.14.84

• based on 2D-NOE NMR (Scheme 3). The enolate 21 was then converted into enolonium species 22 and cross-coupled with a second equivalent of 21 to give the two separable diastereoisomers of 23 one meso and one rac in 6:1 diastereoselectivity. This in conjunction with earlier work from our group [34

An efficient and facile access to highly functionalized pyrrole derivatives

• Meng Gao,
• Wenting Zhao,
• Hongyi Zhao,
• Ziyun Lin,
• Dongfeng Zhang and
• Haihong Huang

Beilstein J. Org. Chem. 2018, 14, 884–890, doi:10.3762/bjoc.14.75

• easily attacked by the nucleophilic amine (compared with the carbonyl at the 4-position, shown in Scheme 4) exemplified by the reaction of 12d with ethylamine to afford 13k. NOESY analysis of 13k was used to confirm the relative positions of 3,4-diamide groups formed. NOE correlations between an H of the

Recent developments in the asymmetric Reformatsky-type reaction

• Hélène Pellissier

Beilstein J. Org. Chem. 2018, 14, 325–344, doi:10.3762/bjoc.14.21

• prepiscibactin through five supplementary steps, including Zn(II)-induced thiazolidine formation followed by lactamization. On the basis of NOE methods, the synthetic prebiscibactin was found spectroscopically indistinguishable from the natural product. More recently, excellent results were also reported by

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• ROESY) also did not provide unequivocal structures of the N-adamantylated derivatives [13][14]. For example, the attachment of an adamantyl group to the N1 or N3 atom in the azole ring of compounds 5 and 6 could not be distinguished by NOE data. Similar problems with the unambiguous determination of the

• the studies of N-alkylated heterocyclic compounds with a high abundance of nitrogen nuclei, where 13C chemical shifts and 1H-1H NOE data cannot provide reliable structural information. The incorporation of the 15N-labels also permitted the study of the mechanism of isomerization of N-adamantylated

Synthesis of ergostane-type brassinosteroids with modifications in ring A

• Vladimir N. Zhabinskii,
• Darya A. Osiyuk,
• Yuri V. Ermolovich,
• Natalia M. Chaschina,
• Tatsiana S. Dalidovich,
• Miroslav Strnad and
• Vladimir A. Khripach

Beilstein J. Org. Chem. 2017, 13, 2326–2331, doi:10.3762/bjoc.13.229

• transformed, on treatment with KOH, into the epoxide 24. The structures of isomeric epoxides 22 and 24 were confirmed by their NOESY spectra as shown in Scheme 4. The obvious NOE correlation between H-3 and H-5 in 24 suggested the spatial vicinity of these two protons, thus the epoxide ring was β-oriented. On

Difunctionalization of alkenes with iodine and tert-butyl hydroperoxide (TBHP) at room temperature for the synthesis of 1-(tert-butylperoxy)-2-iodoethanes

• Hao Wang,
• Cui Chen,
• Weibing Liu and
• Zhibo Zhu

Beilstein J. Org. Chem. 2017, 13, 2023–2027, doi:10.3762/bjoc.13.200

• excellent yields. Especially, according to the detection of NMR and NOE analysis, the substrate 1-methylcyclopent-1-ene (1t) affords (1R,2R)-1-(tert-butylperoxy)-2-iodo-1-methylcyclopentane (2t) as the only product. And even more exciting this reaction was easily scaled up to 10 mmol with no obvious loss in

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159