Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• presented a detailed review on continuous crystallizations of pharmaceutical compounds which discusses these approaches [108]. It is in the field of crystallization where the biggest gap between industry and academia is visible. While industry has large downstream platforms to purify APIs, academia is at a

Navigating and expanding the roadmap of natural product genome mining tools

• Friederike Biermann,
• Sebastian L. Wenski and
• Eric J. N. Helfrich

Beilstein J. Org. Chem. 2022, 18, 1656–1671, doi:10.3762/bjoc.18.178

• identify currently overlooked BGCs Genome mining was pivotal for the expansion of NP chemical space in the past two decades. Despite the development of more and more sophisticated genome mining platforms, in many cases where truly novel NP scaffolds were described, the NP was isolated first and only then

• primary or secondary metabolism (both ends of the spectrum) are identified using the strategies listed below the bar and subsequently excluded from further analysis. gcBGC aims at identifying as-of-yet overlooked BGCs that cannot be detected by state-of-the-art bioinformatic platforms, here referred to as

Microelectrode arrays, electrosynthesis, and the optimization of signaling on an inert, stable surface

• Kendra Drayton-White,
• Siyue Liu,
• Yu-Chia Chang,
• Sakashi Uppal and
• Kevin D. Moeller

Beilstein J. Org. Chem. 2022, 18, 1488–1498, doi:10.3762/bjoc.18.156

• ; microelectrode array; Introduction Microelectrode arrays composed of collections of electrodes that can each be individually addressed are powerful platforms for monitoring interactions between a protein target and small molecules [1][2][3][4][5][6][7][8]. In these efforts, molecules are either placed or

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• , however, that the enantiomeric excess increases with an increase in bond length separation between the phosphorus and the R group. From the reaction evaluation we found that dual activation might be required from the catalyst in certain enantioselective reactions. Thus, CPA platforms that reintroduce a

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• -TAADs with acylated amino groups are highly stable. In contrast, unprotected N-TAADs are prone to cage opening and hydrolysis, yet quaternization of the bridge-head nitrogen greatly stabilizes their structure. We have showcased that N-TAADs can serve as platforms for the design of chelating ligands and

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• -catalyzed cross-coupling reactions, such as arylation reactions catalyzed by Pd2(dba)3/CuI, as well as allylation and methylation reactions catalyzed by CuI⋅PPh3. C3-Benzyldimethylsilyl-appended furfurals are thus introduced as versatile platforms, providing a modular access to 3-substituted 2-furyl

• -based protocol for the catalytic C3–H silylation of furfurylimines [15]. This method allows to install a C–Si bond poised for further functionalization on the furfural unit, and thereby leads to synthetic platforms useful to access elaborated furans. This prospect was demonstrated with platforms relying

• activation [19]. Thereby, C3-triorganosilyl-substituted furfurals could be suitable platforms to develop a two-step modular approach to 3-substituted 2-furyl carbinols, entailing nucleophilic addition to the aldehyde function and oxygen-assisted electrophilic substitution of the C–Si bond (Scheme 1). Results

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• sophisticated platforms such as metal nanoparticles, all of which have been reviewed thoroughly in the literature [4][5][6][7][8]. However, the methods referenced so far display one or more of the following setbacks: involvement of harsh oxidants or reductants, use of expensive metal catalysts, need for

Flow synthesis of oxadiazoles coupled with sequential in-line extraction and chromatography

• Kian Donnelly and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 232–239, doi:10.3762/bjoc.18.27

• significant development in continuous flow platforms, particularly in industry [16][17][18][19][20]. 1,3,4-Oxadiazoles are biologically relevant 5-membered heterocyclic compounds with various favourable pharmacokinetic properties and have been investigated as potential candidates for antiviral, antifungal and

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

Enhanced target cell specificity and uptake of lipid nanoparticles using RNA aptamers and peptides

• Roslyn M. Ray,
• Anders Højgaard Hansen,
• Maria Taskova,
• Bernhard Jandl,
• Jonas Hansen,
• Citra Soemardy,
• Kevin V. Morris and
• Kira Astakhova

Beilstein J. Org. Chem. 2021, 17, 891–907, doi:10.3762/bjoc.17.75

• platforms compatible with antiretroviral drugs. Specifically, a productive CNS delivery of such compounds is expected to reduce HIV-1-associated neurological disorders as well as to reduce HIV-1 replication at this sanctuary site [13][50][51]. We investigated the use of T7 and Tat peptides and evaluated the

Optical detection of di- and triphosphate anions with mixed monolayer-protected gold nanoparticles containing zinc(II)–dipicolylamine complexes

• Lena Reinke,
• Julia Bartl,
• Marcus Koch and
• Stefan Kubik

Beilstein J. Org. Chem. 2020, 16, 2687–2700, doi:10.3762/bjoc.16.219

• introducing a method to assess whether certain biologically relevant anions are present in an aqueous solution within a specific concentration range. Keywords: chemosensor; diphosphate; gold nanoparticles; optical sensing; triphosphate; Introduction Gold nanoparticles (AuNPs) are versatile platforms for the

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• software available to assist with the building up of glycosylated biomolecular systems. As opposed to manual preparation, there are glycan-specific tools and toolkits such as doGlycans [27], Glycosylator [28], and online platforms such as GLYCAM-WEB [29] and CHARMM-GUI [30]. In this work, the CHARMM-GUI

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

• ] and EuroCarbDB [49] and GlycomeDB [50] used GlycoCT [51] (Table 1). Thankfully, data from discontinued glycomics projects are not lost but were integrated into newer platforms, often with novel notations. One such example is GlyTouCan [53], which uses both GlycoCT [54] and WURCS [53] as notation

• languages. As a result, tools that interconvert between notations were developed to successfully integrate old data into new platforms. Additionally, the introduction of tools such as GlycanFormatConverter [55] to convert WURCS notations into more human-readable formats has eased the interpretation of

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

• information, coupled with the emergence of new platforms and technologies, has benefitted glycoscience to the point of enabling the detection and high-resolution determination and representation of complex glycans [1]. Increasing numbers of carbohydrate sequences have accumulated throughout extensive work in

• the tools available for the representation of a simple disaccharide: lactose (β-D-Galp-(1→4)-D-Glcp). Figure 2 shows how different web-available platforms rendered it. On the one hand, thanks to the unified nomenclature, there is no ambiguity regarding the nature of the carbohydrate represented. On

• monosaccharides show striking differences across platforms even though the appropriate colours to be used are strictly defined (https://www.ncbi.nlm.nih.gov/glycans/snfg.html#tab2). The colour discrepancy observed here means that some of the tools do not conform to SNFG standards. For some purposes, this

Hierarchically assembled helicates as reaction platform – from stoichiometric Diels–Alder reactions to enamine catalysis

• David Van Craen,
• Jenny Begall,
• Johannes Großkurth,
• Leonard Himmel,
• Oliver Linnenberg,
• Elisabeth Isaak and
• Markus Albrecht

Beilstein J. Org. Chem. 2020, 16, 2338–2345, doi:10.3762/bjoc.16.195

• processes based on the principle to use self-assembled coordination platforms (or as in the present case mixtures thereof) to control stereoselective C–C bond-forming reactions. Stereoinduction usually relies on spatial proximity of the prochiral carbon atoms and a chiral information of, e.g., a chiral

• formed helicates with mixtures of ligands as platforms to control the stereochemistry of C–C bond-forming reactions. However, it would be of great advantage to transfer the findings to catalytic C–C bond-forming reactions which are catalyzed by hierarchical helicates containing chiral ligands for

Tools for generating and analyzing glycan microarray data

• Akul Y. Mehta,
• Jamie Heimburg-Molinaro and
• Richard D. Cummings

Beilstein J. Org. Chem. 2020, 16, 2260–2271, doi:10.3762/bjoc.16.187

• ://glycosciences.med.ic.ac.uk/data.html. Description: Imperial College Microarray Data Online Portal of glycan microarray data (Figure 3B) consists of ≈160 experiments (from ≈36 publications) on a variety of microarray platforms composed of different glycans. The database includes data on antibodies, animal and plant lectins

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

• for help with the high-content microscopy and analysis, J. A. Kritzer (Tufts University) and M. Hensel (Osnabrück University) for providing materials, and the Bioimaging and ACCESS platforms for services. Funding We thank the University of Geneva, the NCCR Chemical Biology, the NCCR Molecular Systems

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

• new anthelmintics, phenotypic screens involving assays of parasites or models in vitro remain important [83]. As a result, several methods and screening platforms have been developed to improve the screening speed and reliability. In this section we discuss recent phenotyping methods and systems, and

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

• conformational entropy penalty upon binding to a protein target, and the approach of constraining the ligand conformation with a ring is widely used in drug design [2]. Accordingly, with increasing interest for sp3-rich molecules, spirocyclic compounds are being considered valuable as molecular platforms for the

• molecular platforms for the generation of high-quality small molecule collections, taking advantage of their three-dimensional shape and structural bias to develop lead compounds. The combination of multicomponent KA2 and Pauson–Khand reactions using representative cyclic ketones, allylamine and

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• comparatively small number of characterized bacterial terpenes can likely be attributed to three factors: 1) the early misconception that bacteria are not capable of producing complex terpenoids, 2) the lack of genome mining platforms for terpene biosynthetic gene clusters and the inability to perform rational

• NRPSs), bacterial TCs show only little overall sequence similarity [1]. The lack of conservation in primary sequence has slowed down our understanding of terpene cyclization and, as a result, hampered the development of efficient genome mining platforms for the detection of bacterial terpene BGCs

• powerful chemoinformatic platforms is likely to assist in detecting putative terpenoids. In the future, synthetic biology will likely allow the expansion of terpene chemical space by efficiently producing novel terpenes in genome-optimized host strains and the generation of non-natural terpenes through the

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• processes has remained underexploited [27]. Thus, we envisioned that the combination of an Ugi-azide-4CR with modern metal-catalyzed C–C bond-forming methods would enable access to structurally novel compounds featuring hybrid heterocycle platforms. We focused on metal-catalyzed annulation approaches that

Norbornadiene-functionalized triazatriangulenium and trioxatriangulenium platforms

• Roland Löw,
• Talina Rusch,
• Tobias Moje,
• Fynn Röhricht,
• Olaf M. Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1815–1821, doi:10.3762/bjoc.15.175

• 10.3762/bjoc.15.175 Abstract Triazatriangulenium (TATA) and trioxatriangulenium (TOTA) ions are particularly suited systems to mount functional molecules onto atomically flat surfaces such as Au(111). The TATA and TOTA units serve as platforms that absorb onto the surface and form ordered monolayers

• (NBD) and quadricyclanes (QC) attached to TATA and TOTA platforms which can be used to check if these accelerated rates and the spin change mechanism also apply to [2 + 2] cycloreversions (QC→NBD). Keywords: [2 + 2] cycloaddition; [2 + 2] cycloreversion; norbornadiene; photochemical isomerization

• ]. Three molecular units are combined in a modular way to achieve a controlled adsorption on the surface: the platform, a spacer and the functional molecule. Triazatriangulenium (TATA) and trioxatriangulenium (TOTA) units are used as molecular platforms. They adsorb on the surface and form ordered

An azobenzene container showing a definite folding – synthesis and structural investigation

• Abdulselam Adam,
• Saber Mehrparvar and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2019, 15, 1534–1544, doi:10.3762/bjoc.15.156

• are determined by the type and size of the macrocyclic platform, e.g., if all of the amino acid side chains are of the same configuration, they are presented on one face of the macrocycle in a convergent manner. The artificial Lissoclinum cyclopeptide platforms feature C2, C3 and C4 symmetry [3]. So

• strategy and we tried to synthesize the chiral foldable container 10 in a one pot reaction. For this purpose, the platforms 2a and 3a and the dibromide 9 were dissolved in acetonitrile in the ratio 1:1:2.2. To this solution potassium carbonate as base was added and the whole mixture was refluxed for one

• -D3 [56][57] as well as the def2-TZVP [60][61] basis set. Some examples for artificial C2- and C3-symmetric platforms based on Lissoclinum cyclopeptide alkaloids. a) Principle of a chiral foldable platform and container based on Lissoclinum cyclopeptide alkaloids. b) Switchable molecular platform 4

Diazocine-functionalized TATA platforms

• Roland Löw,
• Talina Rusch,
• Fynn Röhricht,
• Olaf Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1485–1490, doi:10.3762/bjoc.15.150

• ” (triazatriangulenium) platforms which adsorb on Au(111) surfaces. A spacer, such as an ethynyl group is connected to the central carbon atom like a post and the azobenzene is mounted on top of the spacer. After preparation of an ordered self-assembled monolayer on gold, the azobenzene units are freestanding upright on

• that are more stable in their trans-configurations [23]. To investigate the electronic coupling effects, we synthesized two diazocine derivatized TATA platforms with ethynyl spacers (diazocine-TATAs). In compound 1 the diazocine is connected to the platform with the ethynyl group in para-position to

• different diazocines mounted on TATA platforms (1, 2). The photochemical switching between the stable cis and metastable trans-isomers was investigated. Upon irradiation with light of 405 nm diazocine-TATAs 1 and 2 convert to their trans-configurations in moderate to good yields. The metastable trans

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• -Enynes are also important building blocks in organic syntheses or platforms for further synthesis [19]. Accordingly, significant efforts have been made to develop efficient syntheses of enynes [17][18][19][20]. The most common routes relied on Wittig-type reactions [21][22] and transition-metal-catalyzed