Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• is a three-step flow-through protocol leading to macrocycles with musk-like olfactoric properties, which was realized under extreme conditions. These include the use of safety-hazardous reaction mixtures, the handling of explosive intermediates, and their pyrolysis at high temperatures (Scheme 17

• . Inductively heated continuous flow protocol for the synthesis of Iso E Super (88) [91][92]. Three-step continuous flow synthesis of macrocycles 89 and 90 with musk-like olfactoric properties. Acknowledgements We thank Dr. J. Panten (Symrise AG, Holzminden, Germany) and Dr. H. Herzog (EVONIK Degussa GmbH

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• differently sized triangles (S)-40 and (S)-41 depending on the length of the organic spacer in the acceptor unit (Figure 9) [75]. Since the interior cavity of the homochiral macrocycles was equipped with BINOL units, they were utilized as catalysts for the asymmetric conjugate addition of chalcone 42 with

Synthesis of a new water-soluble hexacarboxylated tribenzotriquinacene derivative and its competitive host–guest interaction for drug delivery

• Man-Ping Li,
• Nan Yang and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2022, 18, 539–548, doi:10.3762/bjoc.18.56

• , supramolecular chemotherapy has received considerable attention by utilizing a supramolecular strategy to decrease the cytotoxicity of anticancer drugs to normal cells while preserving their cytotoxicity against cancer cells [11]. Supramolecular systems derived from macrocycles [12][13], such as calix[n]arenes

• ) derivatives are a class of molecules possessing a rigid bowl-shaped structure and a C3v-symmetric skeleton [21]. Bearing similarity with macrocycles in general, they can act as versatile hosts for encapsulating guest molecules. Over the past two decades, host–guest interactions and self-assembly based on TBTQ

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• thread also leads to a desymmetrization of the BINOL-based macrocycle (loss of C2 symmetry), as seen by 13C NMR spectroscopy. Stoddart and co-workers also used their π–π-recognition approach for the synthesis of BINOL-containing cationic catenanes [47][48]. They employed BINOL-based macrocycles

• containing electron-rich hydroquinone or 1,5-dioxynaphthalene units (macrocycles 15/21/23), together with suitable dicationic bis-bipyridinium precursors (16/19). Self-assembly of the corresponding pseudorotaxanes by π–π stacking, following by capping with dibromo-p-xylene 17 gave rise to a series of chiral

• ). Next, the authors showed that the application of the chiral BINOL-based bisbipyridinium precursor 19 (in combination with 15 and 17) leads to the corresponding catenane 20, which contains two BINOL-based macrocycles (see Figure 5b). When using (rac)-15 and (R)-19, the (S,R)-diastereomer of the product

Bioinspired tetraamino-bisthiourea chiral macrocycles in catalyzing decarboxylative Mannich reactions

• Hao Guo,
• Yu-Fei Ao,
• De-Xian Wang and
• Qi-Qiang Wang

Beilstein J. Org. Chem. 2022, 18, 486–496, doi:10.3762/bjoc.18.51

• 10.3762/bjoc.18.51 Abstract A series of tetraamino-bisthiourea chiral macrocycles containing two diarylthiourea and two chiral diamine units were synthesized by a fragment-coupling approach in high yields. Different chiral diamine units, including cyclohexanediamines and diphenylethanediamines were

• readily incorporated by both homo and hetero [1 + 1] macrocyclic condensation of bisamine and bisisothiocyanate fragments. With the easy synthesis, gram-scale of macrocycle products can be readily obtained. These chiral macrocycles were applied in catalyzing bioinspired decarboxylative Mannich reactions

• tertiary amine sites were found to be crucial for achieving efficient activation and stereocontrol. As shown in control experiments, catalysis with the acyclic analogues having the same structural motifs were non-selective. Keywords: chiral macrocycles; cooperative asymmetric catalysis; decarboxylative

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• the bonded metal. This crucial aspect prompted their application in supramolecular chemistry as well. Thus, a recent evolution of their chemistry concerns the development of novel architectures in which P(III) compounds are incorporated in cavity-shaped macrocycles [5][6][7][8]. In this scenario

• macrocycles are less exploited in catalysis [28]. The larger macrocycle size, its conformational adaptability, and the possibility to selectively functionalize the macrocycle offered several opportunities to design synthetic receptors and prototypes of nanodevices, instead [29]. In this context, we recently

• via conventional protocols using (Me2S)AuCl. Notably, the organometallic macrocycles A,B,C(AuCl)2 could be isolated via column chromatography separation. Gold(I) catalysts were subsequently fully characterized by NMR analysis and high-resolution mass spectrometry. The conformation of the catalysts, in

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• of macrocycles [49]. The macrocyclisation technique by tryptophan C2–H activation has been further improved showing structurally constrained peptides bearing a side chain connection of tryptophan and phenylalanine or tyrosine [50]. Moreover, a similar Pd-mediated approach for C(sp3)–H activation of

• shown to be a highly effective tool to sample the conformational space of polypeptides made of sequences of 10 to 30 amino acids [87][88] and of macrocycles [89]. Our simulation strategy, mainly adapted from the latter references, made use of 15 independent 700 ns-long aMD simulation runs for each

• the macrocycles was analysed via principal component analysis (PCA) of the non-hydrogen atoms forming the cycle, and the structure of the peptide backbone was investigated via secondary structure analysis and backbone root mean square deviation (RMSD) clustering including amino acids Pro3 to Met15

Synthesis of a novel aminobenzene-containing hemicucurbituril and its fluorescence spectral properties with ions

• Qingkai Zeng,
• Qiumeng Long,
• Jihong Lu,
• Li Wang,
• Yuting You,
• Xiaoting Yuan,
• Qianjun Zhang,
• Qingmei Ge,
• Hang Cong and
• Mao Liu

Beilstein J. Org. Chem. 2021, 17, 2840–2847, doi:10.3762/bjoc.17.195

• Macrocycles with converging binding sites and functional groups hold a key position in supramolecular chemistry, which has been repeatedly confirmed by classic macrocyclic molecules, such as crown ethers, cyclodextrins, calixarenes, cucurbiturils and their homologues [1]. For the past decades, numerous

• intriguing macrocycles have come into our sight, cycloparaphenylenes [2][3][4][5][6][7][8], pillararenes [9][10][11][12], tiaraarenes [13][14], coronaarenes [15][16][17], heteracalixaromatics [18][19], and hemicucurbiturils [20] for instance, and these modified macrocycles have been applied into practical

• . These adverse properties have impeded the development of hemicucurbit[n]urils to some extent. Introducing aromatic fragments into macrocycles which have no chromophore is a viable strategy to expand the scope of their application. Ganin et al. [34] reported the synthesis and formation of several

A study on selective transformation of norbornadiene into fluorinated cyclopentane-fused isoxazolines

• Zsanett Benke,
• Attila M. Remete and
• Loránd Kiss

Beilstein J. Org. Chem. 2021, 17, 2051–2066, doi:10.3762/bjoc.17.132

• of natural products (especially macrocycles) [12], alkaloids [13], amino acids and functionalized biomolecules such as peptides [14][15][16][17][18][19][20] or various drugs [21]. Due to the ring strain, bicyclic systems and derivatives, such as norbornadiene derivatives can easily be converted

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• activity for iodoethynyl groups [63]. Intramolecular cyclization In 2009, Swager’s research group published the synthesis of fluorescent macrocycles based on 1,3-butadiyne-bridged dibenzo[a,j]anthracene subunits via a multistep route (Scheme 30) [64]. They synthesized substituted dibenzo[a,j]anthracenes

Design, synthesis and photophysical properties of novel star-shaped truxene-based heterocycles utilizing ring-closing metathesis, Clauson–Kaas, Van Leusen and Ullmann-type reactions as key tools

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2021, 17, 1374–1384, doi:10.3762/bjoc.17.96

• macrocycles [31][32]. Moreover, polypyrrolic systems are of extensive interest in numerous areas namely optics, medicine, and supramolecular chemistry in addition to the materials sciences and technology. Fascinatingly, in luminescence as well as fluorescence-based sensors, pyrrole derivatives play a vital

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• need of crystallization, using DFT calculations with a high degree of accuracy. Keywords: conformational analysis; crystal engineering; halogenation; macrocycles; porphyrins; Introduction Crystal engineering using porphyrins as a scaffolding unit has been a topic of increasing interest over the past

• the porphyrin macrocycles are stacked with hexyl chains aggregating with each other (6, 3.270(5) Å, Figure 12C) (7, 3.316(4) Å, Figure 12D). Looking at the bond lengths and angles (Supporting Information File 2, Table S2) there are common changes observed when introducing a nickel(II) metal center

• Information File 1, Figure S30) establish the packing pattern seen in Supporting Information File 1, Figure S23. As with compound 1, the stacking between the porphyrin layers is organized with the bromine atoms overlapping with each other at a separation of 3.306(3) Å among the porphyrin macrocycles. In

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• the strategy has further been successfully applied in the total synthesis of bioactive macrocycles and related natural products. In this context, hundreds of valuable contributions have already been made in this area, and the present review is intended to provide the systematic assortment of diverse

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• Minzan Zuo Krishnasamy Velmurugan Kaiya Wang Xueqi Tian Xiao-Yu Hu College of Materials Science and Technology, Nanjing University of Aeronautics and Astronautics, Nanjing, 211106, China 10.3762/bjoc.17.15 Abstract Due to the unique characteristics of macrocycles (e.g., the ease of modification

• with various macrocyclic hosts as well as on the role of macrocyclic-hosts-assisted hybrid materials in energy transfer. To keep the clarity of this review, the macrocycles are categorized into the most commonly used supramolecular hosts, including crown ethers, cyclodextrins, cucurbiturils

• , calixarenes, and pillararenes. This minireview not only summarizes the role that macrocycles play in photocatalytic reactions but also clarifies the photocatalytic mechanisms. Finally, the future research efforts and new pathways to apply macrocycles and supramolecular hybrid materials in photocatalysis are

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• , yielding TTFC7 in one step and with good yield of 69% from the diiodide 1, and exTTFC7 with a good yield (31% over 4 steps) from BC7 (Scheme 1, for the detailed synthetic procedure and characterization data, see Supporting Information File 1, section 1). Both NDI macrocycles NDIC8 and NDIC7 were

• binding entropies in pseudo[2]rotaxanes of A2·PF6 as compared to those formed from A1·PF6. Furthermore, the three crown-7 macrocycles BC7, exTTFC7, and TTFC7 bind A2·PF6 with a binding energy (entries 1, 2, and 4 in Table 1) slightly higher than the crown-8 analogs (entries 5, 6, and 8 in Table 1

• results in a 10–20-fold increase of the binding constants as observed for the weaker binding macrocycles TTFC8 and NDIC8 (Table 1, entries 13 and 14). A1·BArF24 even allows the formation of a pseudo[2]rotaxane with the bisTTFC8 macrocycle (Table 1, entry 15), to which A1·PF6 binds too weakly to determine

Water-soluble host–guest complexes between fullerenes and a sugar-functionalized tribenzotriquinacene assembling to microspheres

• Si-Yuan Liu,
• Xin-Rui Wang,
• Man-Ping Li,
• Wen-Rong Xu and
• Dietmar Kuck

Beilstein J. Org. Chem. 2020, 16, 2551–2561, doi:10.3762/bjoc.16.207

• C60 and C70 [1][2][3][4][5]. It is generally accepted that good complexation of fullerenes requires host molecules with bowl or basket-like shapes, such as calixarenes [6], corannulenes [7][8][9][10], cyclodextrins [11][12][13], cyclotriveratrylenes [14][15][16], and similar macrocycles [17][18][19

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• . Keywords: alkynes; azides; host–guest; macrocycles; molecular knots; Introduction Macrocycles have played a central role in the development of molecular recognition, self-assembled molecular devices, and molecular topology [1][2][3][4][5][6]. For example, early work by Pedersen on crown ethers [1], Lehn

• on cryptands [2], and Cram on hemicarcerands [3] demonstrated that preorganized macrocycles have the ability to act as hosts for various guest cations and compounds. Their seminal work was recognized with the 1987 Nobel Prize in Chemistry. More recently, the 2016 Nobel Prize in Chemistry was won by

• Sauvage, Stoddart, and Feringa for their work on molecular machines [4]. Sauvage [5] and Stoddart [6] extensively used macrocycles in their ground-breaking work on catenanes, rotaxanes, knots, and other topologically novel compounds. Exciting advances in the field of molecular topology continue with novel

The B & B approach: Ball-milling conjugation of dextran with phenylboronic acid (PBA)-functionalized BODIPY

• Patrizia Andreozzi,
• Lorenza Tamberi,
• Elisamaria Tasca,
• Gina Elena Giacomazzo,
• Marta Martinez,
• Mirko Severi,
• Marco Marradi,
• Stefano Cicchi,
• Sergio Moya,
• Giacomo Biagiotti and
• Barbara Richichi

Beilstein J. Org. Chem. 2020, 16, 2272–2281, doi:10.3762/bjoc.16.188

• synthesis of boronic esters. Indeed, ball milling has been successfully exploited for the synthesis of small molecules [4] as well as macrocycles [5][22][23] conjugated with boronic esters and this methodology proved to be by far superior over solution-based methods. In this framework, we decided to exploit

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• silico ionophore design to functional sensor characterization. The biscarbazolylurea moiety was used to synthesize methylene-bridged macrocycles of different ring size aiming to fine tune selectivity towards different carboxylates. Cyclization was achieved with two separate strategies, using either amide

• synthesis to access up to –[CH2]10– macrocycles or acyl halides to access up to –[CH2]14– macrocycles. Seventy-five receptor–anion complexes were modelled and studied with COSMO-RS, in addition to all free host molecules. In order to predict initial selectivity towards carboxylates, 1H NMR relative

• sensor development, the results obtained in this work emphasize the importance of evaluating the binding behavior of receptors in real sensor membranes. Keywords: anion sensors; carboxylates; ionophores; macrocycles; sensor prototype; Introduction In 2013, Otto S. Wolfbeis asked the supramolecular

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• the porphyrin rings are both possible. However, due to the sever 74.1(7)° rotation between the two 24-atom mean planes of the porphyrin macrocycles and the space occupied by the triptycene, creating a hetero π-stacking would form larger voids in the crystals structure. This would be less favored than

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• -tethered BODIPY derivatives serve as a substrate in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, which is known as “click” reaction, allowing for a biological tissue labelling [35][36]. In addition, ethynyl-substituted BODIPYs yield unique π-conjugated BODIPY-based macrocycles by

Light-controllable dithienylethene-modified cyclic peptides: photoswitching the in vivo toxicity in zebrafish embryos

• Sergii Afonin,
• Oleg Babii,
• Aline Reuter,
• Volker Middel,
• Masanari Takamiya,
• Uwe Strähle,
• Igor V. Komarov and
• Anne S. Ulrich

Beilstein J. Org. Chem. 2020, 16, 39–49, doi:10.3762/bjoc.16.6

• , in Figure 3A the peptides 19 and 20 are from series v (homodimers), compounds 16–18 have larger (extended) macrocycles and together with 5 possess a higher net charge and charge density than the rest of the peptides. For the most hydrophobic peptide 11 in the ring-open form, which deviates from the

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

• observed in the 1H NMR spectra of the azobenzene-containing macrocycles 1f and 1 at 25 °C (Supporting Information File 1, Figures S13 and S14). Next, in the absence of Ca2+ ions, 1E was subjected to irradiation into the π–π* band (λmax = 362 nm) and photoisomerization of 1E to 1Z took place, as evidenced