Isolation and characterisation of irinans, androstane-type withanolides from Physalis peruviana L.

• Annika Stein,
• Dave Compera,
• Bianka Karge,
• Mark Brönstrup and
• Jakob Franke

Beilstein J. Org. Chem. 2019, 15, 2003–2012, doi:10.3762/bjoc.15.196

• Withanolides are steroidal lactones widespread in Nightshade plants with often potent antiproliferative activities. Additionally, the structural diversity of this compound class holds much potential for the discovery of novel biological activity. Here, we report two newly characterised withanolides, named

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• syntheses of this compound the general approach which employs the aziridine ester (2R,1'R)-5b as a starting material allows to also obtain its 5'-epimer and norfuranomycin (2S,2'R)-133 [87]. To construct the 2,5-dihydrofurane ring the aziridine alcohol (2R,1'R,1''R)-134 (Scheme 35) [88] was converted to the

Host–guest interactions in nor-seco-cucurbit[10]uril: novel guest-dependent molecular recognition and stereoisomerism

• Xiaodong Zhang,
• Wei Wu,
• Zhu Tao and
• Xin-Long Ni

Beilstein J. Org. Chem. 2019, 15, 1705–1711, doi:10.3762/bjoc.15.166

• designed and prepared the ADA-benzyl-based ammonium guest molecules G1. We synthesized this compound because ADA can form a highly stable complex with Q[7] (the highest reported K value for the ADA·Q[7] complex is 1012 M−1) [29]; while benzylammonium ions can be included in both cavities of Q[7] and Q[6

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

•  2). This compound in reaction with AlCl3 without benzene afforded a mixture of allyl alcohol Z-9 and diene E-10a after aqueous work-up (Table 2, entries 1 and 2). The amount of 2.1 equivalents of AlCl3 is sufficient for activation of this transformation (compared to the amount of AlCl3 in entries 1

Synthesis of pyrrolo[1,2-a]quinolines by formal 1,3-dipolar cycloaddition reactions of quinolinium salts

• Anthony Choi,
• Rebecca M. Morley and
• Iain Coldham

Beilstein J. Org. Chem. 2019, 15, 1480–1484, doi:10.3762/bjoc.15.149

• reaction of quinolinium salts bearing electron-withdrawing groups other than ketones, we prepared ester 4 [55] and amide 5 by alkylation of quinoline. Arylidenemalononitriles such as 6a are known to undergo related chemistry [41], so we heated this compound with the quinolinium salts in the presence of

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• elaborated derivatives [58][59] and the ease of a recently established large-scale synthesis reported by Rousseau and co-workers [60]. Hence, we decided to revisit this compound in order to improve the separation in terms of both better resolution of the enantiomeric bowl-shaped conformers and isolation of

• details). Analysis of the data gave a racemization barrier of 114.3 kJ mol−1 which is in good agreement with the value of 114.0 kJ mol−1 reported by Collet for his experiments in dioxane [62]. Perhaps equally interesting for anyone planning to work with this compound this translates into the following

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• coupling in a low yield of 10% alongside with phthalocyanine byproducts. The triisopropylsilyl-protected derivative 12b could be obtained in a slightly higher yield of 21%, presumably due to the bulkier TIPS-groups. A crystal structure of this compound was obtained (see Supporting Information File 2). To

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

• -producing bacterium Massilia sp. NR 4-1 and predicted to direct the biosynthesis of a molecule that is structurally related to the thiazoline-containing siderophore micacocidin. In order to track this compound, we analyzed the metabolic profiles of Massilia cultures grown under different iron concentrations

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• library of androstanic derivatives 21 (Figure 2B) and their reduced analogues bearing the 3β-hydroxy group were biologically tested showing antifungal activity against Fusarium virguliforme and Fusarium solani. The generation of this compound library suffered from the formation of the Passerini reaction

Novel (2-amino-4-arylimidazolyl)propanoic acids and pyrrolo[1,2-c]imidazoles via the domino reactions of 2-amino-4-arylimidazoles with carbonyl and methylene active compounds

• Victoria V. Lipson,
• Tetiana L. Pavlovska,
• Nataliya V. Svetlichnaya,
• Anna A. Poryvai,
• Nikolay Yu. Gorobets,
• Erik V. Van der Eycken,
• Irina S. Konovalova,
• Svetlana V. Shiskina,
• Alexander V. Borisov,
• Vladimir I. Musatov and
• Alexander V. Mazepa

Beilstein J. Org. Chem. 2019, 15, 1032–1045, doi:10.3762/bjoc.15.101

• (CYP11B2) and 11β-hydroxylase (CYP11B1), which is responsible for cortisol production [35]. This compound is under development for the treatment of Cushing's syndrome and pituitary ACTH hypersecretion [36]. From this point of view the approach to pyrrolo[1,2-c]imidazole moiety by using acyclic methylene

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• comparison with commercially available standards (Figures S6–S9, Supporting Information File 1). The non-enzymatic degradation of GPP as a background reaction to 15 resulted in a substantial loss of stereoinformation for this compound (7% ee). Also the cyclised products 10, 11 and 13 where not obtained in

• most products. However, in the side product 7 C-1 remains untouched after 1,11-cyclisation, which allows to investigate the stereochemical course of the first cyclisation step for this compound. First, the absolute configuration of 7 was assigned as shown in Figure 2 from the incubation experiments

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• of the wavelengths, the electron-withdrawing ALA-amide unit was electronically decoupled from the DAT chromophore by introducing a propylene spacer. Thus, diethyl DAT was first equipped with an N-Alloc-protected 3-aminopropyl side chain at one nitrogen function following a literature protocol. This

• compound, 5, was then submitted to reductive amination with para-(trifluoromethyl)benzaldehyde. After Alloc deprotection, the side chain was amidated with ALA following the same COMU–DIPEA protocol as described for 3. The second target compound 7 was obtained in 59% yield over three steps. Indeed, the

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• 8 showed the highest inhibitory effect of this study with an IC50 of 11 µM corresponding to a 3000-fold improvement compared to the monomer control. This result suggests a higher participation of sugar units in the lectin binding for this compound. Docking calculation for model glycolipids To

A diastereoselective approach to axially chiral biaryls via electrochemically enabled cyclization cascade

• Hong Yan,
• Zhong-Yi Mao,
• Zhong-Wei Hou,
• Jinshuai Song and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2019, 15, 795–800, doi:10.3762/bjoc.15.76

• stereoselectivity of the reaction was not controlled by relative thermodynamic stability of the diastereomers. The major isomer of 3c, which contained a sterically less demanding Ph group at the R1 position (cf. Table 1), did not isomerize at room temperature for 1 year. However, heating a solution of this compound

Synthesis of polydicyclopentadiene using the Cp₂TiCl₂/Et₂AlCl catalytic system and thin-layer oxidation of the polymer in air

• Zhargolma B. Bazarova,
• Ludmila S. Soroka,
• Alex A. Lyapkov,
• Мekhman S. Yusubov and
• Francis Verpoort

Beilstein J. Org. Chem. 2019, 15, 733–745, doi:10.3762/bjoc.15.69

• . Indeed, as reported in previously published papers [15][16], the colored blue complex under these conditions is caused by a compound containing Ti(III) or Ti(IV). This compound corresponds to the final [Cp2TiEt]+·[AlEtCl3]− complex. The presence of an isosbestic point at 656 nm indicates the presence of

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• give α-methoxy carbonyl compound 7. The isolation of this compound supports our mechanistic proposal as shown in Scheme 2 and it shows that sterically very hindered carboxylic acids are probably poor components in the route to β-ketoenamides. A systematic study of this possible limitation was not

• (see Scheme 10). This compound was converted into PM59 by the standard cyclocondensation reaction (Scheme 15) leading to a pyridin-4-ol moiety that was converted to the nonaflate. Compound PM60 bears a pyrimidyl and a pyridinyl substituent at the 2,2’-position of the biphenyl part [41]. Synthesis of

• approach to complex heterocycles. The aldehyde PM69 was further converted into the terminal alkyne PM73 by employing the Bestmann–Ohira protocol (Scheme 21). After its Sonogashira reaction with iodobenzene to the intermediate disubstituted alkyne PM74 this compound was converted into furopyrimidine

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• high importance. Until now, the carbamate-linked methylcyclopropenes Ac4GlcNCyoc and Ac4GalNCyoc are the only cyclopropene derivatives that were examined in this context [25][26]. Ac4GlcNCyoc was used to visualize protein-specific glycosylation inside living cells [32]. However, this compound is

Synthesis and SAR of the antistaphylococcal natural product nematophin from Xenorhabdus nematophila

• Frank Wesche,
• Hélène Adihou,
• Thomas A. Wichelhaus and
• Helge B. Bode

Beilstein J. Org. Chem. 2019, 15, 535–541, doi:10.3762/bjoc.15.47

• that showed nanomolar activity against S. aureus [20]. To the detriment of this compound class, all derivatives lose their antibacterial activity in the presence of serum in vitro in serial broth and agar dilution method [16][20]. Even with the use of charged groups as modifiers, serum-protein binding

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• (Scheme 11B). This compound does not react under the initial reaction conditions, but can be forced to do so in a Joullié MCR with a new isocyanide/carboxylic acid pair [47]. Incidentally, this last process is also remarkably stereoselective, something very unusual in Ugi-type reactions. Finally, to

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• (TFDA) [68] to a solution of propargyl glycolates 64a–n containing NaF in diglyme at 120 °C. Difluorocyclopropene 65a could be purified by flash chromatography on silica gel and was isolated in 86% yield but this compound rapidly underwent decomposition upon storage. The instability of glycolates 65a–n

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

• summer season in the highland areas of Japan (e.g., Nagano and Iwate prefectures) was isolated. The structure of a toxin produced by this organism was analyzed based on the detailed evaluation of its 2D NMR and FABMS spectra, and this compound has not been reported previously. We propose the name

• compound has not been reported previously; we propose the name cichorinotoxin for this compound. Very recently, Huang et al. reported new phytotoxins, named cichopeptin A and B, from P. cichorii SF1-54 [14], which cause midrib rot disease in lettuce much like cichorinotoxin. However, cichorinotoxin is

• subjected to reversed-phase HPLC (the same ODS column) using MeOH/H2O (58:42) with 0.3% NH3 and afforded 6 major peaks. After purification, only one peak remained in the HPLC chromatogram, and this compound was analyzed by FABMS. To clarify the stereochemistry of the amino acids present, Marfey’s method was

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• a protected serinal (R)-23 [54]. Wittig olefination extended the alkyl chain by two carbon atoms and simultaneously installed the C=C bond which was subjected to the intramolecular epoxidation to give a >20:1 mixture of aminoepoxides with the isomer (2S,3R,4R)-117 dominating. Without isolation this

• compound underwent another intramolecular cyclization in the 5-exo mode to form the oxazolidinone 118. To complete the synthesis of (2S,3S,4S)-4 the secondary hydroxy group was protected as a pivalate, the hydroxymethyl fragment was oxidized after hydrolysis of the silyl ether and finally all protecting

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• NMe-3I-HHQ (10), however, the resulting NMe-PQS derivative 12 was only isolated in low yield (14%). Presumably, this compound is not too stable during the final oxidation step as significant amounts of oxidative side products including N-methylisatin were obtained, which also impeded the isolation of

• the desired product 12. Nevertheless, enough material could be obtained to enable biological investigations on this compound. Growth inhibition of S. aureus To get a better understanding of the influence of methylation on the antibiotic properties of AQ compounds, their effect on the growth of S