Identification of volatiles from six marine Celeribacter strains

• Anuj Kumar Chhalodia,
• Jan Rinkel,
• Dorota Konvalinkova,
• Jörn Petersen and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 420–430, doi:10.3762/bjoc.17.38

• mass spectra to library spectra and of retention indices [38] to tabulated literature data (Table 1), or by a direct comparison to authentic standards. The structures of the identified compounds are shown in Figure 2. While the headspace extracts from C. marinus, C. neptunius and C. manganoxidans were

• 41 showed strong similarities to the library mass spectrum of 2-mercaptobenzothiazole that has a molecular weight of 167 Da. The isotope pattern of the molecular ion at m/z = 213 indicated the presence of three sulfur atoms. The strong base peak at m/z = 167 in the mass spectrum of 41 suggested a

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• library of these versatile carbamate building blocks (3, ca. 1 mmol scale), we decided to apply a scavenger column to perform in-line purification. This was achieved as previously reported [22] based on a mixture of Amberlyst A21 (a tertiary amine, ca. 2 equiv) and Amberlyst A15 (a sulfonic acid, ca. 2

• purification of a small library of valuable Cbz-carbamates (see Figure 1). Furthermore, the CALB column was effectively used over several days after purging with toluene to prevent cross contamination. The scale-up of this flow process was demonstrated on a 100 mmol scale showcasing the robust nature of this

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• , protein folding, and potentially small-molecule library screening, as it can broaden the accessibility of quantitative NMR spectroscopy to a wider range of laboratories. Ligand-observed protein binding interactions In addition to protein-observed fluorine (PrOF) NMR spectroscopy, ligand-observed fluorine

• ] which is a binding assay, and fluorine atoms for biochemical screening (n-FABS) methodology which is a functional assay [39][40]. Both of these methods have been successfully used for ligand-based screening, fragment-based functional screening and dynamic library screening, and have been recently

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

• Michael Andresini,
• Leonardo Degannaro and
• Renzo Luisi

Beilstein J. Org. Chem. 2021, 17, 203–209, doi:10.3762/bjoc.17.20

• corresponding 2H-azirines in a microfluidic reactor, overcoming the hazards associated with this transformation under batch conditions. A small library of functionalized aryl and alkyl-substituted NH-aziridines has been created under operationally simple conditions. Notably, the addition reaction was found to

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• hours in neat P(OEt)3 at 160 °C. With the experimental conditions in hand, the SNAr–Arbuzov reaction between 2,6-bistriazolylpurines 6a–i and P(OEt)3 provided a library of novel purine phosphonates 4a–i in 27–82% yield (Table 3). The products 4a, 4d, 4e, and 4i were easily precipitated from hexane left

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• investment in route scouting and optimization. This full paper focuses on the synthesis issues that we encountered during our route exploration and the original solutions we found that helped us to identify two optimized library-style processes to prepare our large kinase inhibitor library. Keywords: 7

• -azabenzotriazole; hinge-binder; ionic hydrogenation; library; pyridine-2(1H)-one; Introduction During a recent medicinal chemistry program targeting a kinase to treat skin disorders, we identified the 4-amino-3-carboxamide disubstituted pyridine-2(1H)-one motif (1) as an interesting starting point. Recently, both

• library building block acid chloride 2. The libraries were prepared in a 3-step manner: 1) amide coupling; 2) deprotection of the 2-methoxypyridine through hydrolysis at elevated temperatures; and 3) the final SNAr or Ullman step to introduce the amine vector with variable yields and chromatographic

Regioselective synthesis of heterocyclic N-sulfonyl amidines from heteroaromatic thioamides and sulfonyl azides

• Vladimir Ilkin,
• Vera Berseneva,
• Tetyana Beryozkina,
• Tatiana Glukhareva,
• Lidia Dianova,
• Wim Dehaen,
• Eugenia Seliverstova and
• Vasiliy Bakulev

Beilstein J. Org. Chem. 2020, 16, 2937–2947, doi:10.3762/bjoc.16.243

• (Table 1, entry 11 and Table 2, entry 14). Thus solvent-free conditions, a temperature of 88 °C and a thioamide/azide ratio of 1:2.5 are optimal to prepare N-sulfonyl amidine 1c (entry 11, Table 1). Next, these optimized conditions were used for the synthesis of a small library of 1-alkyl-1,2,3-triazoles

• amidines 3t–aa in good yields (Scheme 3). Thus, a library of N-sulfonyl amidines bearing differently substituted 1,2,3-triazoles was successfully prepared. Among them are compounds bearing an NH-unsubstituted 1,2,3-triazole ring which gives extra possibilities for the modification of the molecules by the

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• -sorting, and integrative vs non-integrative self-sorting. A completive self-sorting makes full use of all constituents in a given library, whereas an incomplete self-sorting describes mixtures containing one or several aggregates along with unused components. The integrative self-sorting [30] on the other

• -interlocked catenanes. When both cages were mixed without C70, the dynamic combinatorial library (DCL) of seven compositionally distinct mixed-ligand Zn4L6 cages was observed (Figure 5b). An efficient self-sorting was only observed after the addition of the guest C70. As expected, the cage [Zn4(8')6]8

• . e) A solvent change from CDCl3 to [d8]-toluene leads to a 2-fold completive self-sorting upon treatment with C60. (a) Two new Zn4L6-type cages. (b) The encapsulation of C70 induced distinct reconstitutions within a dynamic library of mixed ligand Zn4L6 cages. The formation of octahedral cages (a

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• identification of terpenes requires either the direct comparison to an authentic standard, or, since such a standard is not always available, a very good match of the measured mass spectrum to a library spectrum and of the measured retention index to literature data. Mass spectrometric fragmentations proceed

Ring-closing metathesis of prochiral oxaenediynes to racemic 4-alkenyl-2-alkynyl-3,6-dihydro-2H-pyrans

• Viola Kolaříková,
• Markéta Rybáčková,
• Martin Svoboda and
• Jaroslav Kvíčala

Beilstein J. Org. Chem. 2020, 16, 2757–2768, doi:10.3762/bjoc.16.226

• substrate failed (Scheme 7). Next, the alkylated diynols 7b, 7c, and 8b–d were deprotected using standard methodologies affording the products in moderate to good yields (Scheme 8). With the diynols 4a–d in hand, we were able to synthesize a small library of allylated oxaenediynes 2 by the alkylation of the

Leveraging glycomics data in glycoprotein 3D structure validation with Privateer

• Haroldas Bagdonas,
• Daniel Ungar and
• Jon Agirre

Beilstein J. Org. Chem. 2020, 16, 2523–2533, doi:10.3762/bjoc.16.204

• intermediate interconversion library. A foundation for such interconversion libraries exists in the form of the carbohydrate validation software Privateer. The program is able to compute individual monosaccharide conformations from a glycoprotein model, check whether the modelled carbohydrates atomistic

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• protein–protein interactions, Valenti et al. used 1H,15N-TROSY-HSQC spectra of 15N,2H-labeled 14-3-3ΔC in combination with ligand-based WaterLOGSY experiments for the screening of a compound fragment library [107]. Screening by HSQC NMR spectra is more robust compared to ligand-detected NMR methods or

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• monosaccharides, substituents and linkages from the list of symbols. However, some wrong combinations of choices can block the interface, resulting in the need to re-start the process (SugarSketcher is on version beta 1.3). Alternatively, SugarSketcher also uses GlycoCT or a native template library as an input. A

• ][20] to define the input of these tools. Technically, the tool provides an interactive interface which allows an automated glycan rendering using a library of individual monosaccharides or pre-built template structures (Figure 6, middle). GlycanBuilder provides access to 41 templates. They include N

• ] (available at https://jcggdb.jp/idb/flash/GlycoEditor.jsp) is an online software for drawing glycans. Through a straightforward interface, three ways of input are possible: by JCGGDB ID, through a library of common oligosaccharides and by direct input. A list of most common monosaccharides is presented, and

GlypNirO: An automated workflow for quantitative N- and O-linked glycoproteomic data analysis

• Toan K. Phung,
• Cassandra L. Pegg and
• Benjamin L. Schulz

Beilstein J. Org. Chem. 2020, 16, 2127–2135, doi:10.3762/bjoc.16.180

• robustness and throughput. Our workflow uses a collection of scripts built on an in-house sequence string handling library and the scientific Python data handling package pandas [24], and integrates outputs of two commonly used software packages in glycoproteomic MS data analysis, Proteome Discoverer (Thermo

• included, parsed from the online UniProtKB database using an inhouse Python library. Statistical analyses Significant differences in glycoform abundances between healthy and diseased samples were evaluated using an unpaired two-tailed t-test without corrections for multiple comparisons. Missing values were

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

• Mysore Bhyrappa Harisha,
• Pandi Dhanalakshmi,
• Rajendran Suresh,
• Raju Ranjith Kumar and
• Shanmugam Muthusubramanian

Beilstein J. Org. Chem. 2020, 16, 2108–2118, doi:10.3762/bjoc.16.178

• just at the start of the reaction and b is the photograph after the completion of the reaction. Further, the utility of the thiol group in 3 for the generation of a library of compounds was demonstrated by the simple acetylation and alkylation (Scheme 4 and Scheme 5). The acetylation of the thiol group

Automated high-content imaging for cellular uptake, from the Schmuck cation to the latest cyclic oligochalcogenides

• Rémi Martinent,
• Javier López-Andarias,
• Dimitri Moreau,
• Yangyang Cheng,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2020, 16, 2007–2016, doi:10.3762/bjoc.16.167

• library of 259 molecular tweezers through an ethidium bromide (EB) displacement assay, show a negligible DNA transfection efficiency (Figure 3). However, the derivative 15, with two lipophilic hydrocarbon chains, results in a remarkable DNA delivery and transfection [35]. These two hydrocarbon chains

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• species are GL4, the product of GlfT1 and GL5, the product of GlfT2. In the presence of 10 mM 1bα the predominant bands are GL3 and GL4, the products of GlfT1, which could point to a GlfT2 inhibition. Conclusion In summary, a small library of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones 1‒3 was

• structures do not include the uridine mimicking part which can increase the binding affinity significantly. Attaching of this part is a topic of further synthesis and second-generation compound library preparation. We believe that our further efforts, both in synthetic and computational fields, will point to

Pauson–Khand reaction of fluorinated compounds

• Jorge Escorihuela,
• Daniel M. Sedgwick,
• Alberto Llobat,
• Mercedes Medio-Simón,
• Pablo Barrio and
• Santos Fustero

Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138

• and co-workers [73] allowed the efficient preparation of a small library of substrates bearing aryl, alkyl, and alkenyl substitutents. These were isolated after complexation to Co2(CO)8 as the corresponding adducts 64, due to difficulties in their isolation. Subsequent heating with norbornadiene

• afforded the corresponding products 59 in good to excellent yields (Scheme 36). The authors then studied the elimination of the trifluoromethyl group from this library of PK adducts, building upon their own experience in the field (vide supra, Scheme 34). Thus, by subjecting enones 59 to treatment with DBU

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• ) spectrometer equipped with a Prodigy cryo-probehead. The pulse programs were taken from the Bruker software library (TopSpin 3.5) and full 1H and 13C assignments were achieved with widely accepted strategies [34][35]. 1H NMR assignments were accomplished using general knowledge of chemical shift dispersion

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• for peptides can be powerful tools for labeling or inhibition. Finding those binding motifs, especially in water which competes for intermolecular H-bonds, poses an enormous challenge. A dynamic combinatorial library can be a powerful method to overcome this issue. We previously reported artificial

• receptors emerging form a dynamic combinatorial library of peptide building blocks. In this study we aimed to broaden this scope towards recognition of small peptides. Employing CXC peptide building blocks, we found that cyclic dimers of oxidized CFC bind to the aromatic peptides FF and YY (K ≈ 229–702 M−1

• . A more general approach for the development of artificial receptors can be the use of a dynamic combinatorial library (DCL). In a DCL a large variety of molecules is generated by a dynamic exchange of building blocks. The dynamic nature of those exchange reactions is essential since it allows the

Photocatalyzed syntheses of phenanthrenes and their aza-analogues. A review

• Alessandra Del Tito,
• Havall Othman Abdulla,
• Davide Ravelli,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 1476–1488, doi:10.3762/bjoc.16.123

• the bromoalkanes through an oxidative quenching mechanism [48]. Phenanthridines may be also formed by the initial addition of an electrophilic radical onto isonitriles. Thus, a library of 6-alkylated phenanthridines (5.2a–d in Scheme 5) and other nitrogen-based heterocycles have been prepared from

• highly regioselective strategy for the synthesis of a library of polyheteroaromatic compounds under photocatalytic conditions was reported (Scheme 13). The process made use of fac-Ir(ppy)3 (0.3 mol %) as the photoredox catalyst and occurred at room temperature under extremely mild conditions. The

Anthelmintic drug discovery: target identification, screening methods and the role of open science

• Frederick A. Partridge,
• Ruth Forman,
• Carole J. R. Bataille,
• Graham M. Wynne,
• Marina Nick,
• Angela J. Russell,
• Kathryn J. Else and
• David B. Sattelle

Beilstein J. Org. Chem. 2020, 16, 1203–1224, doi:10.3762/bjoc.16.105

• compound screening efforts, and participating in distributed open library screening projects such as the Medicines for Malaria Venture Pathogen Box. The point has recently been made by Tim Geary and colleagues that millions of compounds have been screened in industrial and academic labs on isolated

• . They screened a compound library against both adult and free-living larval stages (egg to L3i larval development assay, E2L) of the human hookworm parasite Ancylostoma ceylanicum and against C. elegans. They found that the A. ceylanicum E2L assay was more successful at identifying compounds active

• interest [116]. WormScan is a method that uses a flatbed scanner to capture sequential images, where the scanner high-intensity light usefully stimulates the worm movement [117]. This system has been utilised to screen a 26000 compound library in a C. elegans growth assay [119]. An updated version of this

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

• Dragana Vuk,
• Irena Škorić,
• Valentina Milašinović,
• Krešimir Molčanov and
• Željko Marinić

Beilstein J. Org. Chem. 2020, 16, 1092–1099, doi:10.3762/bjoc.16.96

• methodology [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. By using a simple photochemical procedure, it was possible to obtain a whole library of novel bicyclo[3.2.1]octadiene derivatives, available for further functionalization, which could enable the easier investigation of the relationship

• bicyclo[3.2.1]octadiene derivatives with a structure convenient for the introduction of new functional groups. Further on, the study aimed at expanding the compound library and at creating preconditions for further biological investigations. This work represents a rational continuation of the research [17

Accelerating fragment-based library generation by coupling high-performance photoreactors with benchtop analysis

• Quentin Lefebvre,
• Christophe Salomé and
• Thomas C. Fessard

Beilstein J. Org. Chem. 2020, 16, 982–988, doi:10.3762/bjoc.16.87

• thus be rapidly accessed, identifying privileged or challenging scaffolds and paving the way for further exploration. Keywords: benchtop analytics; fragment-based library; heterocyclic sp2–sp3 fragments; N-arylation; photoredox-nickel dual catalysis; Introduction Heterocyclic sp2–sp3 fragments are

• initiated a high-throughput program of fragment-based library generation and after shortcomings using more classical cross-coupling conditions, we turned our attention to the photoredox-nickel dual-catalysis strategy recently reported by MacMillan and Buchwald [10]. The reported conditions use lower

• temperatures and a mild base. Inspired by work at Merck on chemical informers, we decided to exploit our library of spirocyclic amines and strained scaffolds to generate a focused list of potential products [13]. We wanted to perform parallel reactions on small scale to gain further knowledge on the reactivity

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

• /secondary amine oxidation under continuous-flow conditions using TPP as photocatalyst for singlet oxygen generation, and subsequently, the product imines were trapped with trimethylsilyl cyanide (TMSCN) for producing the α-aminonitriles (Scheme 56) [105]. A library of α-aminonitriles was produced by this