HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• ]; and 3) access to larger macrocycles with n > 4 is not a trivial task usually leading to reaction yields <10% [21][38][42][60]. Herein, we report 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as an efficient solvent to speed up reaction times and also capable of tolerating electron-deficient and halogenated

• translated to the formation of other macrocycles as long as they share a similar reaction mechanism. (a) Control experiment testing deiodination of 2-iodoresorcinol. (b) Molecular crystal structure of chlorinated resorcin[4]arenes 1h and 1i, and carboxylic acid-containing 1s at 100 K. Thermal ellipsoids are

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• the importance of DPMs in mind due to their utmost significance as a building block in the construction of porphyrinogens, related polypyrrolic macrocycles, and pigments [39][40][41]. As shown in Figure 1, these DPMs and many more have fruitfully been used by several research groups in sensing/binding

Radical reactivity of antiaromatic Ni(II) norcorroles with azo radical initiators

• Siham Asyiqin Shafie,
• Ryo Nozawa,
• Hideaki Takano and
• Hiroshi Shinokubo

Beilstein J. Org. Chem. 2024, 20, 1967–1972, doi:10.3762/bjoc.20.172

• species has remained unexplored. Here, we disclose the radical functionalization of Ni(II) norcorroles with simple and frequently used azo radical initiators to furnish nonconjugated macrocycles with bowl-shaped structures [27]. The photophysical and electronic properties of the obtained products are also

• subsequent demetallation. Conclusion In conclusion, we have investigated the addition reaction of electrophilic alkyl radicals derived from azo radical initiators to antiaromatic Ni(II) norcorroles. The reaction smoothly proceeded to afford bowl-shaped nonconjugated macrocycles 2a in excellent yield, which

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

Discovery of antimicrobial peptides clostrisin and cellulosin from Clostridium: insights into their structures, co-localized biosynthetic gene clusters, and antibiotic activity

• Moisés Alejandro Alejo Hernandez,
• Katia Pamela Villavicencio Sánchez,
• Rosendo Sánchez Morales,
• Karla Georgina Hernández-Magro Gil,
• David Silverio Moreno-Gutiérrez,
• Eddie Guillermo Sanchez-Rueda,
• Yanet Teresa-Cruz,
• Brian Choi,
• Armando Hernández Garcia,
• Alba Romero-Rodríguez,
• Oscar Juárez,
• Siseth Martínez-Caballero,
• Mario Figueroa and
• Corina-Diana Ceapă

Beilstein J. Org. Chem. 2024, 20, 1800–1816, doi:10.3762/bjoc.20.159

• ). Furthermore, analysis of the MS2 experiment post-iodoacetamide reaction indicated the absence of free cysteines between C30 and C39, supported by alkylated y35 and y24 ions, implying macrocyclization, and proposed the presence of three macrocycles between G41 and the C-terminus (Figure S3 in Supporting

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• aldehyde at the C6 sidechain. Furthermore, the fusion protein, JuvD-RhFRED, enabled regio- and diastereoselective epoxidation of the C12 double bond of macrocycles 80–82, culminating in the total synthesis of M-4365 A1 (83), M-4365 A3 (juvenimicin A4, 84), and M-4365 A2 (juvenimicin A3, 85), respectively

Introduction of peripheral nitrogen atoms to cyclo-meta-phenylenes

• Koki Ikemoto and
• Hiroyuki Isobe

Beilstein J. Org. Chem. 2024, 20, 1207–1212, doi:10.3762/bjoc.20.103

• biased charges on the peripheral nitrogen atoms. Keywords: cross coupling; macrocycles; nitrogen doping; UV–vis spectroscopy; X-ray charge density analysis; Introduction Graphitic carbonaceous sheets of graphene continue to attract considerable attention, which lead us to explore structural defects

• 3a and 3b resembled those of the hydrocarbon congeners, forming one-dimensional columns of stacked macrocycles (Figure 3b). The electronic effects of the nitrogen dopants in 3a were examined with X-ray charge density analyses [10][16]. For the crystal structures shown in Figure 3, we used a standard

• configurations preferred over T-shaped stackings [22]. In our study, we observed that pyridine–pyridine stacks were preferred in the crystal stacking (Figure 3), which might be attributed to the biased ESPs on the macrocycles. Finally, we found that nitrogen locations altered chemical characteristics of nitrogen

Chemoenzymatic synthesis of macrocyclic peptides and polyketides via thioesterase-catalyzed macrocyclization

• Senze Qiao,
• Zhongyu Cheng and
• Fuzhuo Li

Beilstein J. Org. Chem. 2024, 20, 721–733, doi:10.3762/bjoc.20.66

• polyketides; thioesterase; Introduction Nonribosomal peptides, polyketides, and their hybrids exhibit significant diversity and a broad spectrum of bioactivities [1][2][3]. Particularly, macrocycles from these three categories of natural products are vital resources for developing pharmaceuticals and drug

• possible and provides a potential to construct the analogs library of these bioactive macrocycles for further biological investigations. This review presents representative examples of chemoenzymatic approaches for macrocyclic peptides, polyketides, and their hybrids employing TE domains, and particular

• aforementioned NPRS macrocycles, the synthesis of macrocylic polyketides and PKS/NRPS hybrids is more challenging due to the absence of a streamlined preparation strategy such as solid-phase peptide synthesis (SPPS). In enzymology studies, it was common to hydrolyze the cyclic natural products in order to obtain

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• beautiful structures and intriguing properties. We present herein a new synthetic strategy to access [2]rotaxanes, namely active-metal template clipping. We discuss the design of the target [2]rotaxanes, synthesis and characterization of the axle, macrocycle precursors and macrocycles as well as preparation

• CuAAC click chemistry [38][39][40]. The choice of CuAAC as key step to accomplish the synthesis of the [2]rotaxanes was motivated by its high efficiency [41]. In addition, this reaction proved its versatility for rotaxanes synthesis [15], including chiral [2]rotaxanes [42]. The macrocycles M1 and M2

• -functonalized stopper 3 after substitution of bromine with azide. The dialkyne-decorated pyridine 5 was prepared starting from 2,6-bis(bromomethyl)pyridine that was reacted with compound 4, under phase transfer catalysis (Scheme 1). Finally, the axle 6, as well as the reference macrocycles M1 and M2 [44], were

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• materials science [10]. These two classes of molecules seem particularly remarkable among the endless family of macrocyclic compounds due to their unique features and easy accessibility. The popularity of porphyrins and crown ethers has been so extensive that the whole range of these macrocycles is even

• macrocycles is shown. As several topics were reviewed earlier, we did not intend to present an exhaustive overview but instead focused on presenting selected examples of molecules of fundamental importance in this research area. The more interested readers are referred to excellent review articles focused on

• specific classes of macrocycles, such as crowned porphyrins [22], calixpyrroles [26][27][28][29], Schiff porphyrinoids [30], expanded porphyrinoids [31][32], or carbaporphyrinoids [33][34], and a selection of articles dedicated to crown ether chemistry [17][20][35][36][37]. Historical Perspective Various

Unravelling a trichloroacetic acid-catalyzed cascade access to benzo[f]chromeno[2,3-h]quinoxalinoporphyrins

• Chandra Sekhar Tekuri,
• Pargat Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2023, 19, 1216–1224, doi:10.3762/bjoc.19.89

• ; multicomponent synthesis; one-pot reaction; trichloroacetic acid; Introduction π-Conjugated porphyrin macrocycles are known for their applications in numerous areas ranging from oxygen transport, photosynthesis, catalysis and medicine [1][2][3]. In the past several years, diverse organic scaffolds have been

• incorporated at the porphyrin periphery and different metal ions in the porphyrin core to modulate ground-state and excited-state characteristics of easily accessible meso-tetraarylporphyrins. Some of these π-extended tetrapyrrolic macrocycles have emerged as potential candidates in photodynamic therapy and

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• publications carried out on cyclodextrins (CDs) and their market growth are clear evidence of the undying interest in these macrocycles discovered in 1891 [1]. It seems that these supramolecules still have not revealed all their secrets and are still stimulating curiosity in fundamental and applied research

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• supramolecular gels (Figure 2a) [52]. Upon irradiation using a UV-light-emitting diode (LED) and a visible LED as sources, the reversible cleavage of the trithiocarbonate stoppers was accomplished, thus allowing the dethreading [53] of the wheels to take place by the shuttling of the macrocycles along the thread

• cyclobutanes (Figure 4b). Interestingly, the changes in the crystalline array as a consequence of this photodimerization within the cucurbituril macrocycles also induced a macroscopic deformation of the metal-organic material, promoting a photomechanical bending of the crystals. This photomechanical

pH-Responsive fluorescent supramolecular nanoparticles based on tetraphenylethylene-labelled chitosan and a six-fold carboxylated tribenzotriquinacene

• Nan Yang,
• Yi-Yan Zhu,
• Wei-Xiu Lin,
• Yi-Long Lu and
• Wen-Rong Xu

Beilstein J. Org. Chem. 2023, 19, 635–645, doi:10.3762/bjoc.19.45

• supramolecular systems derived from water-soluble macrocycles, including cyclodextrins (CDs), calix[n]arenes (CXs), cucurbiturils (CBs), and pillararenes have been widely studied [2][6][7][8]. Similar to those macrocyclic acceptors, tribenzotriquinacene (TBTQ) derivatives, a class of versatile host molecules

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• Jorge de Lima Neto Paulo Henrique Menezes Universidade Federal de Pernambuco, Departamento de Química Fundamental, Recife-PE, 50740-560, Brazil 10.3762/bjoc.19.31 Abstract The combretastatin D series and its analogues, corniculatolides and isocorniculatolides belong to a class of macrocycles

• ; macrocycles; Introduction Conceptually, cyclic molecules containing more than 12 covalently connected atoms are called macrocycles and this class comprises several structurally distinct compounds [1]. Due to their structural characteristics and their different biological activities, the isolation of new

• macrocycles and their synthesis finds several examples described in the literature and has already been the subject of review articles [2][3][4]. More recently, cyclic diaryl ether heptanoids (DAEH) [5], another class of macrocycles has been attracting attention not only because of their structural and

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• supramolecular catalysts were based on covalent hosts, typically cyclodextrin macrocycles [1], which had an interior hydrophobic cavity decorated with catalytically useful functional groups. Recently, increased emphasis has been placed on catalysis that takes use of noncovalent hosts, including self-assembled

• of novel supramolecular catalysts. In their contribution Wang and co-workers [17] reported an interesting example of chalcogen bonding catalysis approach for the synthesis of calix[4]pyrrole macrocycles. The Se···O=C chalcogen bonding interactions between a selenide-based catalyst and the carbonyl

• tetraaminobisthiourea chiral macrocycles as catalysts in decarboxylative Mannich reactions. Low macrocycle loading was used to catalyze the decarboxylative addition of malonic acid half thioesters to isatin-derived ketimines with excellent yields and good enantioselectivity. It was reported that effective activation

Synthesis of meso-pyrrole-substituted corroles by condensation of 1,9-diformyldipyrromethanes with pyrrole

• Baris Temelli and
• Pinar Kapci

Beilstein J. Org. Chem. 2022, 18, 1403–1409, doi:10.3762/bjoc.18.145

• amount of pyrrole is presented for the first time. This procedure is a simple and efficient way for the preparation of corroles with a polymerizable substituent on meso-positions. Keywords: corrole; dipyrromethane; macrocycles; metal triflates; pyrrole; Introduction Corroles, a member of contracted

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• can be highly beneficial. Therefore, Skowerski and co-workers constructed a tube-in-tube reactor for the ring-closing metathesis of dienes 62 and 63 to macrocycles 65 or 66, respectively, mediated by ruthenium catalyst 64 (Scheme 15) [53]. The substrate and the catalyst are mixed in a Q-piece and

• temperature of 70 °C and a residence time of 30 min, macrocycles 65 and 66 are obtained in excellent yields with a preference for the E-isomers as determined by GC/MS analysis. Although, macrocycles 65 and 66 are, to the best of our knowledge, not used as musks in perfumery, this work demonstrates the value

• cyclohexanone in flow. Synthesis of macrocyclic olefine 60 by ring-closing metathesis of diene 58 in a continuously stirred tank reactor (CSTR). Synthesis of macrocycles 65 and 66 by ring-closing metathesis of dienes 62 or 63, respectively, in a tube-in-tube reactor removing the formed ethylene. Z-Selective

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