Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• requires very mild reaction conditions in only three steps, with moderate to high yields in short reaction times under flow conditions [29], and it is compatible with substituents with different electronic properties (electron-releasing or electron-withdrawing) in the 4-arylidene ring. In addition, the

• source and a Q-ToF mass analyzer. Acetonitrile and methanol were used as solvents. Samples were introduced at a continuous flow of 0.2 mL/min, and nitrogen served both as the nebulizer gas and the dry gas. Infrared spectra were recorded on a Spectrum 100 Perkin-Elmer FTIR spectrophotometer, with a

Synthesis of novel multifunctional carbazole-based molecules and their thermal, electrochemical and optical properties

• Nuray Altinolcek,
• Ahmet Battal,
• Mustafa Tavasli,
• William J. Peveler,
• Holly A. Yu and
• Peter J. Skabara

Beilstein J. Org. Chem. 2020, 16, 1066–1074, doi:10.3762/bjoc.16.93

• 602E electrochemical workstation with iR compensation using dry dichloromethane. Thermogravimetric analysis was conducted using a Netzsch TG 209 F3 Tarsus Thermogravimetric Analyser under a constant flow of nitrogen. Differential scanning calorimetry was determined on a Netzsch DSC 214 Polyma

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• -phenylalanine (70) was prepared by direct fluorination of 4-borono-ʟ-phenylalanine (BPA, 69) with [18F]AcOF or [18F]F2. The reaction was followed by a HPLC separation using a Delta-Pak Cl8 cartridge 0.1% acetic acid as the mobile phase at a flow rate of 10 mL/min. The product was isolated in radiochemical

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• conjugated photosensitizers show increasing potential in photocatalysis since they combine both photo- and electrochemical properties which can substitute available metalloorganic photocatalysts. Batch and continuous-flow approaches are presented highlighting the relevance of enabling technologies for the

• ) [1][2][3]. This effect limits the penetration of photons to only a short distance into the reaction vessel, provoking increases of the reaction time, photocatalyst loading, byproducts, overheating and so on. Notably, the use of continuous-flow reactors for photochemical applications allows us to

• continuous-flow photochemistry a sustainable alternative approach being applied already by the chemical and pharmaceutical industries. Porphyrinoid is the term given for a class of organic compounds containing four pyrrole rings connected by four methylene bridges, and include porphyrin, chlorin

A method to determine the correct photocatalyst concentration for photooxidation reactions conducted in continuous flow reactors

• Clemens R. Horn and
• Sylvain Gremetz

Beilstein J. Org. Chem. 2020, 16, 871–879, doi:10.3762/bjoc.16.78

• maxima close to the absorption maximum of each catalyst. Keywords: catalyst concentration; channel height; flow chemistry; photooxidation; Introduction The renaissance of photochemistry that occurred over the last decade has been described as “old light through new windows”, and much of this work

• centered on the combination of light with continuous flow reactors [1][2][3][4][5][6]. The reason for this increased interest is that continuous flow photochemical reactors can overcome various limitations that occur when the same reaction run in batch reactors [7]. For example, the flow reactor can

• little as possible” [8]. This phrase describes the approach used to scale up flow reactors to an industrial scale [9][10]. This is particularly true when it comes to biphasic reactions, like a gas/liquid reaction as is the case for photooxidations [11]. An interesting aspect of photooxidations is that

Photocatalytic deaminative benzylation and alkylation of tetrahydroisoquinolines with N-alkylpyrydinium salts

• David Schönbauer,
• Carlo Sambiagio,
• Timothy Noël and
• Michael Schnürch

Beilstein J. Org. Chem. 2020, 16, 809–817, doi:10.3762/bjoc.16.74

• David Schonbauer Carlo Sambiagio Timothy Noel Michael Schnurch Institute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163, 1060 Vienna, Austria Department of Chemical Engineering and Chemistry, Micro Flow Chemistry and Synthetic Methodology, Eindhoven University of Technology, Den

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• peroxide bridge, has been subject of extensive scientific investigations during the last decade [53][54][55][56][57][58][59][60][61][62][63]. In this context, Seeberger and co-workers successfully developed an ingenious continuous-flow process for the hemisynthesis of pure artemisinin from

Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition

• Sivaraman Balasubramaniam,
• Sajith Vijayan,
• Liam V. Goldman,
• Xavier A. May,
• Kyra Dodson,
• Sweta Adhikari,
• Fatima Rivas,
• Davita L. Watkins and
• Shana V. Stoddard

Beilstein J. Org. Chem. 2020, 16, 628–637, doi:10.3762/bjoc.16.59

• an ESI–TOF mass spectrometer (Agilent 6220 Time-of-Flight), gas temperature – 350 °C, drying gas (N2) – 8.0 L/min, mobile phase(s): methanol with 0.1% formic acid, flow rate: 0.2 mL/min, sample preparation: The sample was dissolved in 1 drop of chloroform and diluted with 1 mL methanol. Additional

Synthesis of disparlure and monachalure enantiomers from 2,3-butanediacetals

• Adam Drop,
• Hubert Wojtasek and
• Bożena Frąckowiak-Wojtasek

Beilstein J. Org. Chem. 2020, 16, 616–620, doi:10.3762/bjoc.16.57

• -2,3-Disubstituted butanediacetal derivatives of dimethyl tartrates 9–11 can be converted to cis-isomers 12–14 (Scheme 2) [32]. Compound 12 can be obtained from trans-dimethyl ester 9 in a two-step procedure either following a traditional way or using continuous flow chemistry [32][33][34]. The

Opening up connectivity between documents, structures and bioactivity

• Christopher Southan

Beilstein J. Org. Chem. 2020, 16, 596–606, doi:10.3762/bjoc.16.54

• millions effectively burying these relationships in PDFs over many decades but must now spend millions more trying to get them back out. The key imperative for this is to increase the flow into structured open databases. The positive impacts will include expanded data mining opportunities for drug

• in minutes. Unfortunately, no journals have yet instigated a flow of author-specified DARCP directly into open databases. Progress may come from trends such as open science, open access (OA), findable, accessible, interoperable and reusable (FAIR), resource description framework (RDF) and WikiData

• accelerate the progress and impact of medicinal chemistry. To achieve this the community needs to increase the outward flow of experimental results locked-up in millions of published PDFs into structured open databases that explicitly capture the connectivity between structures, documents and bioactivity

KOt-Bu-promoted selective ring-opening N-alkylation of 2-oxazolines to access 2-aminoethyl acetates and N-substituted thiazolidinones

• Qiao Lin,
• Shiling Zhang and
• Bin Li

Beilstein J. Org. Chem. 2020, 16, 492–501, doi:10.3762/bjoc.16.44

• synthesis of β-nitrate ester carboxamides using tert-butyl nitrite as the nitro source and oxygen as the oxidant through the ring opening of 2-oxazolines [9] (Scheme 1a). Kappe reported a two-step continuous-flow synthesis of N-(2-aminoethyl)acylamides through ring opening/hydrogenation of oxazolines with

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• moderate to good yields. Notably, alkyl iodides were also suitable substrates. The methodology proved to be compatible with a broad range of functional groups. To demonstrate the synthetic utility of the process, the reaction was developed under continuous flow conditions to afford an easy and

• synthesized in 57% yield. Importantly, the reaction scale was increased to 1 g under continuous flow conditions. Then, the reaction was extended to the cyclization of a stilbene derivative into phenanthrene in a moderate 23% isolated yield. To explain the reaction pathway, the authors suggested an oxidative

• mechanism. One year later, 2013, Collins and co-workers extended this concept to the synthesis of carbazole derivatives under continuous flow conditions (Scheme 30) [44]. Using, the [Cu(I)(dmp)(xantphos)]BF4 catalyst, the oxidative cyclization of various triarylamines was carried out in the presence of I2

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

Visible-light-induced addition of carboxymethanide to styrene from monochloroacetic acid

• Kaj M. van Vliet,
• Nicole S. van Leeuwen,
• Albert M. Brouwer and
• Bas de Bruin

Beilstein J. Org. Chem. 2020, 16, 398–408, doi:10.3762/bjoc.16.38

• under the applied reaction conditions. The photoredox activation of monochloroacetic acid leads to the formation of precipitate during the reaction (see Figure 4), again indicating catalyst precipitation/deactivation. Works in the group of Noël and others have revealed that flow chemistry can increase

• shell. We anticipated that in a flow setup using tubing with a small internal diameter (0.71 mm) the photocatalyzed reaction pathways could be more efficient. However, in this case, performing the reaction under flow conditions did not lead to better results. The reaction performed in a flow reactor led

• to a combined yield of 32% within 1 hour. Furthermore, as in a normal reactor, we also observed formation of precipitate in the flow setup, forming clusters of solids. These solids presumably consist of the oxidized or otherwise deactivated photocatalyst. More insight into the selectivity for either

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• -accessible chemical space. Experimental General procedure (A) for the KA2 coupling reaction. CuI (0.2 equiv) was added in a dry sealed vial for microwave synthesis under a nitrogen flow. Then, ketone (1 equiv), alkyne (1.2 equiv) and amine (1.2 equiv) were successively added under a nitrogen flow, and the

• Pauson–Khand (C) reaction. In a dry round bottom flask under a nitrogen flow Co2(CO)8 (0.1 equiv), N,N,N’,N’-tetramethylthiourea (0.6 equiv) and a solution of the enyne compound (1 equiv) were successively added in dry toluene (20 mL/mmol). Then, the reaction mixture was kept under a CO atmosphere and

Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst

• Abhijit Paul,
• Debnath Chatterjee,
• Srirupa Banerjee and
• Somnath Yadav

Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16

• ]. Noël and co-workers reported the C3–H olefination of indoles using Pd(OAc)2 as a catalyst and molecular oxygen as the oxidant under continuous flow conditions [29]. Jia et al. reported the synthesis of 3-alkenylindoles using Pd(OAc)2 as the catalyst and MnO2 as the oxidant under ball milling conditions

Potent hemithioindigo-based antimitotics photocontrol the microtubule cytoskeleton in cellulo

• Alexander Sailer,
• Franziska Ermer,
• Yvonne Kraus,
• Rebekkah Bingham,
• Ferdinand H. Lutter,
• Julia Ahlfeld and
• Oliver Thorn-Seshold

Beilstein J. Org. Chem. 2020, 16, 125–134, doi:10.3762/bjoc.16.14

• cycle arrest in the G2/M phase by preventing the completion of mitosis [1]. We examined cell cycle repartition by quantification of cellular DNA content via propidium iodide (PI) incorporation, which was analysed by flow cytometry (Supporting Information File 1, Figure S7). HeLa cells were treated for

Reversible photoswitching of the DNA-binding properties of styrylquinolizinium derivatives through photochromic [2 + 2] cycloaddition and cycloreversion

• Sarah Kölsch,
• Heiko Ihmels,
• Jochen Mattay,
• Norbert Sewald and
• Brian O. Patrick

Beilstein J. Org. Chem. 2020, 16, 111–124, doi:10.3762/bjoc.16.13

• –d were further investigated by circular dichroism (CD) and flow linear dichroism (LD) spectroscopy [74][75] in phosphate buffer at different ligand-to-DNA ratios (LDR). The mixtures of compounds 3a–d with ct DNA showed clear induced circular dichroism (ICD) and LD bands in the absorption region of

• at 473 nm and 583 nm, respectively, in the presence of DNA, along with a weaker positive signal at 346 nm (Figure 4A1). For LD spectroscopic analysis, the DNA molecules were oriented in a hydrodynamic field of a rotating couette (flow linear dichroism). The corresponding LD spectra were the result of

Functionalization of the imidazo[1,2-a]pyridine ring in α-phosphonoacrylates and α-phosphonopropionates via microwave-assisted Mizoroki–Heck reaction

• Damian Kusy,
• Agata Wojciechowska,
• Joanna Małolepsza and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 15–21, doi:10.3762/bjoc.16.3

• heterogeneous and homogeneous catalysts, as well as continuous-flow conditions [13][14][15]. Therefore, we tested microwave heating, a technique which is known for significant acceleration of the C–C coupling reaction [16]. We carried out the optimization studies using model substrates – compound 1a and benzyl

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• 100% solvent B for 5 min, with a flow rate of 20 mL/min. Thereby, UV detection was performed at 210, 280, and 354 nm. Fractions were collected and pooled according to the observed peaks. The separation yielded two fractions including compound 1 (5.4 mg) and 2 (2.4 mg) at retention times tR 43–44 and

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• to dryness. The residual solid (53 mg) was applied to the preparative HPLC (Cosmosil Cholester Packed Column, 10 × 250 mm, Nacalai Tesque) using a linear gradient of 40 to 70% MeCN in 0.1% HCO2H over 25 min at a flow rate of 4 mL/min, yielding karimunone A (1, 7.3 mg, tR 15.6 min) and B (2, 4.2 mg

• isolated from fraction 4 of ODS chromatography (5:5), which was derived from fraction 3 of silica gel fractionation (10:1), using a linear gradient of 40 to 70% MeCN in 0.1% HCO2H over 25 min at a flow rate of 4 mL/min. Physicochemical data including 1H and 13C NMR spectroscopic data of compounds 3–7 were

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• lipoarabinomannan (LAM) analogs in urine samples using the Alere lateral flow urine (LF)-LAM assay [13]. However, the low sensitivity of the Alere assay limits its scope. Glycan array screening of more than 100 monoclonal antibodies against more than 60 synthetic glycans related to the mycobacterial cell wall

• protecting groups, whereby Fmoc was cleaved by piperidine (20 vol % in DMF), while Lev was removed using hydrazine acetate. Iterative cycles continued until the desired structure was obtained. The oligosaccharide products were cleaved from the solid support using a flow UV photoreactor, followed by a two

Carbazole-functionalized hyper-cross-linked polymers for CO₂ uptake based on Friedel–Crafts polymerization on 9-phenylcarbazole

• Dandan Fang,
• Xiaodong Li,
• Meishuai Zou,
• Xiaoyan Guo and
• Aijuan Zhang

Beilstein J. Org. Chem. 2019, 15, 2856–2863, doi:10.3762/bjoc.15.279

• NETZSCH TG 209F1 TG analyzer for 40–800 °C at a heating rate of 10 °C min−1 under a nitrogen flow of 50 mL min−1. The X-ray diffraction (XRD) patterns of the as prepared polymers were collected using a PANalytical X’pert Pro MPD diffractometer with Cu Kα radiation at room temperature, with step size of

Photoreversible stretching of a BAPTA chelator marshalling Ca²⁺-binding in aqueous media

• Aurélien Ducrot,
• Arnaud Tron,
• Robin Bofinger,
• Ingrid Sanz Beguer,
• Jean-Luc Pozzo and
• Nathan D. McClenaghan

Beilstein J. Org. Chem. 2019, 15, 2801–2811, doi:10.3762/bjoc.15.273

• operated at room temperature. Samples were introduced by injection through a 20 μL sample loop into a 4500 μL/min flow of methanol from the LC pump. Electronic absorption spectra were measured on a Varian Cary 5000 UV–vis–NIR spectrophotometer. Steady-state emission spectra were recorded on a

An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent

• Nicky J. Willis,
• Elliott D. Bayle,
• George Papageorgiou,
• David Steadman,
• Benjamin N. Atkinson,
• William Mahy and
• Paul V. Fish

Beilstein J. Org. Chem. 2019, 15, 2790–2797, doi:10.3762/bjoc.15.271

• ]. Following single oral dose (p.o.) of 10 mg/kg, plasma exposure was high and plasma clearance was low relative to liver blood flow resulting in a plasma elimination half-life of 8.8 hours. The plasma parameters from these mouse PK experiments (Cmax and AUC) are consistent with published preclinical PK data