Skeletocutins M–Q: biologically active compounds from the fruiting bodies of the basidiomycete Skeletocutis sp. collected in Africa

• Tian Cheng,
• Clara Chepkirui,
• Cony Decock,
• Josphat C. Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2782–2789, doi:10.3762/bjoc.15.270

• , solvent A: H2O + 0.1% formic acid, solvent B: acetonitrile + 0.1% formic acid, elution gradient: 5% solvent B for 0.5 min, increasing solvent B to 100% within 19.5 min, 100% solvent B for 5 min, flow rate: 0.6 mL/min, UV–vis detection at λ = 200–600 nm) and ESI–TOF–MS analysis (maXis™ system, Bruker, scan

• ), respectively, were used as mobile phases (elution gradient: 50% solvent B, increasing solvent B to 100% within 60 min, 100% solvent B for 5 min, flow rate: 40 mL/min, UV–vis detection at 210, 254, and 350 nm). Eight fractions (F1–F8) were collected, in accordance with the observed signals. F1 was further

• purified by RPC using solvent A and solvent B (elution gradient: 45% solvent B for 3 min, increasing solvent B to 100% within 18 min, 100% solvent B for 4 min). A Kromasil® C18 HPLC column (Nouryon, column size: 250 mm⋅20 mm, packing: 7 μm, flow rate: 15 mL/min) was used as stationary phase. This led to

Diversity-oriented synthesis of spirothiazolidinediones and their biological evaluation

• Sambasivarao Kotha,
• Gaddamedi Sreevani,
• Lilya U. Dzhemileva,
• Milyausha M. Yunusbaeva,
• Usein M. Dzhemilev and
• Vladimir A. D’yakonov

Beilstein J. Org. Chem. 2019, 15, 2774–2781, doi:10.3762/bjoc.15.269

• spirothiazolidinediones via a [2 + 2 + 2] cyclotrimerization reaction and the derivatives were further functionalized through DA chemistry and click reaction. Using flow cytometry, it was shown for the first time that the new benzyl alcohol derivatives of thiazolidine-2,4-dione generated here are efficient apoptosis

• inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell lines. Keywords: apoptosis; biologically active; [2 + 2 + 2] cycloaddition; flow cytometry; spiro thiazolidinedione; Introduction Heterocyclic compounds play a vital role in the metabolism of all living cells. Thus, most of the biologically active

• the culture of Jurkat cells at a concentration of 0.75 nM and was 68.65%. Under similar conditions, compound 20 showed about 95% in K562 cells of late apoptosis and compound 17 about 30.28% for cell line U937. The results of flow cytometry showed that in all three cell lines, Jurkat, K562 and U937, a

Progress in metathesis chemistry

• Karol Grela and
• Anna Kajetanowicz

Beilstein J. Org. Chem. 2019, 15, 2765–2766, doi:10.3762/bjoc.15.267

• pills are now truly user friendly. Olefin metathesis catalysts can work under homo- or heterogeneous conditions, as well as under continuous flow. The stability of Ru–methylidene species (an attribute important for a successful ethenolysis process) has been significantly improved. Importantly, we have

A photochemical determination of luminescence efficiency of upconverting nanoparticles

• Baptiste Amouroux,
• Clément Roux,
• Jean-Claude Micheau,
• Fabienne Gauffre and
• Christophe Coudret

Beilstein J. Org. Chem. 2019, 15, 2671–2677, doi:10.3762/bjoc.15.260

• run with limited lab equipment. The technique is robust and simple to operate. Concerning the use of single-UCNP as nanolight sources, the emitted flow of photon is rather sparse but yet relevant biological signals could be triggered. This study shows the interest to use P-photochromic dyes as

Unexpected one-pot formation of the 1H-6a,8a-epiminotricyclopenta[a,c,e][8]annulene system from cyclopentanone, ammonia and dimethyl fumarate. Synthesis of highly strained polycyclic nitroxide and EPR study

• Sergey A. Dobrynin,
• Igor A. Kirilyuk,
• Yuri V. Gatilov,
• Andrey A. Kuzhelev,
• Olesya A. Krumkacheva,
• Matvey V. Fedin,
• Michael K. Bowman and
• Elena G. Bagryanskaya

Beilstein J. Org. Chem. 2019, 15, 2664–2670, doi:10.3762/bjoc.15.259

• using a commercial Bruker Elexsys E580 X/Q-band spectrometer equipped with an Oxford helium flow cryostat and temperature control system. An ER 4118X-MD5W resonator was used for X-band measurements. Tm was measured using a two-pulse electron spin echo (ESE) sequence; T1 was measured using the inversion

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• (300 mL) and defatted using hexanes (2 × 500 mL) to give the crude extract. Initial fractionation of culture A (13.5 g) was achieved using Sephadex LH-20 size-exclusion chromatography in methanol (25 × 600 mm). The crude extract was loaded onto the column and eluted with methanol at a flow rate of 4 mL

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• vinylphosphonium ion, and a proton transfer finally yields the 1,4-betaine. A kinetic study of the PPh3/DMAD/Meldrum’s acid reaction by spectrophotometric and stopped-flow methods has been published [14]. The initial 1,3-betaine has also been trapped with other electrophiles. The stable 1,4-betaines betaines III

Synthetic terpenoids in the world of fragrances: Iso E Super^® is the showcase

• Alexey Stepanyuk and
• Andreas Kirschning

Beilstein J. Org. Chem. 2019, 15, 2590–2602, doi:10.3762/bjoc.15.252

• ; march 2019), a low-priced counterpart from TOP2BASE (middle, 20 € per 100 mL) and product produced in our laboratories under flow conditions. Note, although both samples provide a similar smell, the olfactory effects slightly vary because of different proportions of products and isomers produced in very

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• explosive azide chemistry involved in a proposed Tamiflu route by taking advantage of the continuous-flow technology. The azide intermediates were safely synthesised in full conversions and >89% isolated yields. Keywords: azide chemistry; continuous flow synthesis; hazardous; safe; Tamiflu; Introduction

• 1a is a potentially explosive compound because of its nitro and azide moieties [14] and its safety concerns need to be dealt with for large scale synthesis. Safety in this reaction was achieved by in situ formation and consumption in flow of the hazardous intermediates (azide 1a and isocyanate 1b

• ) (Scheme 1 and Figure 1). Continuous-flow synthesis offers the generation and consumption of dangerous intermediates in situ preventing their accumulation, thus it represents a potential solution for dealing with hazardous reaction intermediates and products [15]. Additionally, microreactors can handle

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• -acetylation using NaOMe in MeOH followed by hydrogenolysis in a ThalesNano continuous flow hydrogenation assembly using a 10% Pd-C cartridge [29]. After three cycles of hydrogenation, formation of the target pentasaccharide 1 was evident from the mass spectrum (Scheme 4). Conclusion In conclusion, the

α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA

• Shital K. Chattopadhyay,
• Subhankar Ghosh,
• Sarita Sarkar and
• Kakali Bhadra

Beilstein J. Org. Chem. 2019, 15, 2524–2533, doi:10.3762/bjoc.15.245

• 11b has been studied since it was the most cytotoxic among all. FITC (fluorescein-5-isothiocyanate)–annexin V/PI flow cytometry of HepG2 cells On HeLa cells, the efficacy of 11b was measured through the application of other apoptotic parameters like phosphatidylserine (PS) externalization, a known

• treated with 11b of 2.5 and 4.0 μg/mL concentrations at 37 °C for 24 h. Quantification of ROS by FACS Cells (2 × 105) were treated with SAHA, 11b, 11f, 11g at GI25, GI50 and GI75 concentrations for 24 h and the levels of intracellular ROS were assessed by flow cytometry after incubating with DCFH-DA (25

• ]. Percent of cell death by LDH assay at GI50 dose after 24 h incubation. Comparison between quantitative assays of ROSa generation induced by four compounds by DCFH-DA in HeLa cells through flow cytometric analysis. Percent apoptotic cellsa in presence and absence of 11b by FITC-Annexin-V/PI staining by

Indium-mediated C-allylation of melibiose

• Christian Denner,
• Manuel Gintner,
• Hanspeter Kählig and
• Walther Schmid

Beilstein J. Org. Chem. 2019, 15, 2458–2464, doi:10.3762/bjoc.15.238

• :1, v/v) and subsequently cooled to −78 °C. Ozone was bubbled through the reaction with a gas inlet tube until a clear blue color was observed (2 min). Subsequently, the O3 generation was stopped allowing the gas flow to purge the reaction mixture for additional 15 min. PPh3 (80 mg, 0.305 mmol, 2

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• dehydrogenation process to afford the target product. Also in 2015, Li and co-workers [146] developed a mild and fast Cu(I/II)-catalyzed trifluoromethylation procedure to obtain 3-trifluoromethylcoumarins. The reaction was carried out with a CuCl/CF3SO2Na/TBHP system under continuous-flow conditions, affording

Isolation of fungi using the diffusion chamber device FIND technology

• Benjamin Libor,
• Henrik Harms,
• Stefan Kehraus,
• Ekaterina Egereva,
• Max Crüsemann and
• Gabriele M. König

Beilstein J. Org. Chem. 2019, 15, 2191–2203, doi:10.3762/bjoc.15.216

• with autoclaved deionized water to remove sediment and soil and opened under a laminar air flow cabinet. Each agar plug was transferred to a corresponding agar plate for cultivation. The agar plates contained the same minimal nutrient medium as the agar solution into which the central plate was dipped

• remove sediment and soil and opened under a laminar air flow cabinet to transfer each agar plug to a corresponding agar plate for cultivation. For transfer into 96 well plates a Boekel replica plater was used to punch all agar plugs from the central plate into the corresponding wells containing liquid

Characterization of two new degradation products of atorvastatin calcium formed upon treatment with strong acids

• Jürgen Krauß,
• Monika Klimt,
• Markus Luber,
• Peter Mayer and
• Franz Bracher

Beilstein J. Org. Chem. 2019, 15, 2085–2091, doi:10.3762/bjoc.15.206

• an RP18 stationary phase (Eurospher 100–C18), isocratic elution with 0.01 M ammonium acetate buffer (pH 4)-acetonitrile 54:46 (v/v) at a flow rate of 1 mL/min at 40 °C, with UV detection at 246 nm (Figure 3). Discussion In this investigation we first confirmed some pathways of decomposition of

α-Photooxygenation of chiral aldehydes with singlet oxygen

• Dominika J. Walaszek,
• Magdalena Jawiczuk,
• Jakub Durka,
• Olga Drapała and
• Dorota Gryko

Beilstein J. Org. Chem. 2019, 15, 2076–2084, doi:10.3762/bjoc.15.205

• , with the flow rate set at 1.5 mL/min. The retention times were 7.3; 7.9; 9.4 and 13.4 min for (2S,3R), (2R,3S), (2R,3R) and (2S,3S), respectively. Alcohol 9 was obtained as a colorless oil, 25 mg, 45%. 1H NMR (400 MHz, CDCl3) δH 7.30–7.25 (m, 2H, ArH), 7.22–7.10 (m, 6H, ArH), 7.06–7.04 (m, 2H, ArH

• -6, 14 mg, 23%), diastereosomer anti-6 (2S,3R-6, 22 mg, 36%), respectively. The relative ratio of stereoisomers was determined by HPLC analysis: Daicel Chiralpak ID (250 mm × 4.6 mm), hexane/AcOEt, 80:20 (v/v) flow rate 1.5 mL/min. The retention times were 7.3; 7.9; 9.4 and 13.4 min for (2S,3R), (2R

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

• separated by preparative LC–MS. The sample was dissolved in MeOH to a concentration of 15 mg/mL. 100 µL was injected per run. A separation gradient was used [solvent A: H2O + 0.05% formic acid; solvent B: acetonitrile + 0.045% formic acid; gradient: 10% to 90% B over 10 min, 20 mL/min]. The post-column flow

• was split (100:1) and the minority flow made up to 1 mL/min with MeOH + 0.045% formic acid for in-line analysis by UV, ELSD and MS. The majority flow was collected. The following peaks were collected and identified by NMR: tR = 5.8–6.0 min (irinan A (2), 6 mg); 7.2–8.0 min (4β-hydroxywithanolide E (1

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• −1 to 245 °C (5 min). The injector was operated at 250 °C in the splitless mode. Helium was used as carrier gas at a constant flow of 1.0 mL min−1 and an initial inlet pressure of 166 kPa. The transfer line was maintained at 250 °C and the analytes were ionized by operating in electron impact (EI

Tautomerism as primary signaling mechanism in metal sensing: the case of amide group

• Vera Deneva,
• Georgi Dobrikov,
• Aurelien Crochet,
• Daniela Nedeltcheva,
• Katharina M. Fromm and
• Liudmil Antonov

Beilstein J. Org. Chem. 2019, 15, 1898–1906, doi:10.3762/bjoc.15.185

• Kα1 radiation (λ = 1.54186 Å). The crystal was kept at 250(2) K during data collection by an Oxford Cryosystem open-flow cryostat. Using Olex2 [30], the structure was solved with the ShelXT [31] structure solution program using Intrinsic Phasing and refined with the ShelXL [31] refinement package

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• ; flow rate = 4.0 mL/min; temperature 25 °C). (d) CD and (e) UV–vis spectra of racemic P5A-DPA, the first and second fractions (10 μM) in CHCl3 at 25 °C. (a) CD, (b) UV–vis and (c) fluorescence spectra of the RP5A-DPA (20 μM) in THF and THF/H2O solvent mixtures; inset: the normalized fluorescence

Water inside β-cyclodextrin cavity: amount, stability and mechanism of binding

• Stiliyana Pereva,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2019, 15, 1592–1600, doi:10.3762/bjoc.15.163

• flow calibration of the DSC was made by evaluating the melting peak of pure In and Zn. Dry nitrogen was used as purge gas at a fixed flow rate of 20 mL min−1. All DSC and DTA/TG measurements were repeated three times to ensure reproducibility and accuracy of the determined quantities. Computational

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

• Proteo 90 Å column (C12; 250 × 4.60 mm). Flow rate 1 mL min−1. Eluent A: H2O/CH3CN/TFA (trifluoroacetic acid – TFA) (95:4.9:0.1), eluent B: CH3CN/H2O/TFA (95:4.9:0.1). Preparative RP-HPLC was carried out with a Thermo Separation Products system consisting of a UV-1000 detector and a P-4000 pump equipped

• 300 Å column (C18; 250 × 21.20 mm). Flow rate 7.5 mL min−1. Eluent A: H2O/CH3CN/TFA (95:4.9:0.1), eluent B: CH3CN/H2O/TFA (95:4.9:0.1) Synthesis The synthesis of glycosylated threonine building blocks containing ʟ- or ᴅ-Thr residues was performed according to a previously published route [26]. The

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• /water (supplemented with 0.05% TFA) at a flow rate of 1 mL/min. The product 6 was isolated at tR = 24 min, which was consistent with the metabolic experiment’s data. 1H NMR (500 MHz, chloroform-d) δH 7.65 (d, J = 8.9 Hz, 2H), 7.08 (d, J = 8.9 Hz, 2H), 3.89 (s, 1H), 1.81 (t, J = 18.4 Hz, 1H); 19F NMR

• achieved by reversed-phase HPLC in a Phenomenex Luna SP column, with 60:40 AcCN/water (supplemented with 0.05% TFA) at a flow rate of 1 mL/min, which afforded 11 in 30% yield. The product 11 was isolated at tR = 37 min, which was consistent with the metabolic experiments’ data. 1H NMR (500 MHz, chloroform

• detector and CVM-20A controller module), equipped with a Phenomenex semi-preparative Luna C18 column. Purification of the metabolites was carried out by HPLC, using an eluent system of 60:40 AcCN/water (both supplemented with 0.05% TFA), at a flow rate of 1 mL/min. For this, the extracts were redissolved

Efficiency Eff_syn of complex syntheses as multicomponent reactions, its algorithm and calculations based on concrete criteria

• Heiner Eckert

Beilstein J. Org. Chem. 2019, 15, 1425–1433, doi:10.3762/bjoc.15.142

• soft criteria. Case study All listed and possible constellations of reactions and reaction groups in a complex synthesis are shown in a flow diagram (Scheme 1) and are presented in a detailed case study; the data were inserted into the general efficiency algorithm [2][3]. Although publications usually

Formation of an unexpected 3,3-diphenyl-3H-indazole through a facile intramolecular [2 + 3] cycloaddition of the diazo intermediate

• Andrew T. King,
• Hugh G. Hiscocks,
• Lidia Matesic,
• Mohan Bhadbhade,
• Roger Bishop and
• Alison T. Ung

Beilstein J. Org. Chem. 2019, 15, 1347–1354, doi:10.3762/bjoc.15.134

• of sulfur dioxide. DABSO was selected as it would provide a facile method and is a safer alternative to sulfur dioxide gas [7][8][9][10]. The target molecule 4 was envisaged via the diazonium salt of 5 [11] and 6 and was a modification of the microfluidic flow reaction reported by Malet-Sanz et al