Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• , photocatalysts, and electrocatalysts are presented here. The effect of macrocyclic structural modifications such as their functionalization with different substituents, distortion from planarity, conformational flexibility and rigidity towards catalytic activity are presented, highlighting the potential of these

• and separation technology [3][4][5][6][7][8]. Conversely, porphyrins are connected via methine (=CH-) bridges, resulting in an 18 π-electron macrocyclic system affording macrocyclic planarity as well as unique photophysical and electrochemical properties (Figure 1b). While corroles share similarities

• these macrocyclic catalysts is in a very nascent stage. In this review, the recent advancement in the field of metal-free macrocycles for catalysis will be summarized; mainly focused on porphyrins and calix[4]pyrroles and in the field of organocatalysis, photocatalysis, and electrocatalysis. Review 1

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• light on the mechanism of the γ-CD hydration and to address some unanswered questions: (i) what are the preferable locations for water molecules in the macrocyclic cavity (“hot spots”); (ii) what are the major factors contributing to the stability of the water cluster in the CD interior; (iii) what type

• characteristic; Introduction Cyclodextrins (CDs), the remarkable macrocyclic molecules with significant impact on our daily life, have completed their 130th anniversary in 2021 [1]. These cavitands are made of 6–9 glucose fragments, linked with 1-4 α-glycosidic bonds. Most common is the β-CD with 7 glucose

• substituted/modified CDs. Recent studies combining experimental methods with molecular modeling have revealed that the maximum number of water molecules entrapped inside the macrocyclic cavity is 6 for α-CD [13] and 10 for β-CD [14]. Notably, the exact number of the encapsulated water molecules by γ-CD and

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

• -shaped conformation it precipitates out of solution acting as a thermodynamic sink [5][6]. Shortly after, Cram et al. recognized the potential of resorcin[n]arenes as compounds large enough to encapsulate other simple molecules or ions and group them with other known macrocyclic arene compounds, e.g

• reported herein may impact the synthesis of other macrocyclic arene species, e.g., calix[n]arenes, calix[4]pyrroles, pillar[n]arenes, and cucurbit[n]urils [90][91][92]. Perspective Supramolecular chemistry is a mature field that has crossed boundaries into many other scientific areas. However, the work

• area to analyze ingrained synthetic protocols towards macrocyclic arenes and challenge them as there may be many gems awaiting discovery. Conclusion Introduction of HFIP to the synthesis of resorcin[n]arenes accelerates their reaction time significantly to under one hour for simple and commonly used

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

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

• using an enzyme or at what stage in a synthesis the enzyme is employed: 1) regio- and stereoselective late-stage functionalization of core scaffolds, 2) in situ generation of highly reactive intermediates, and 3) the one-step construction of macrocyclic or fused multicyclic scaffolds via regio- and

• carboxylic acids followed by intramolecular condensation. As a chemo-enzymatic complementary strategy, thioesterase (TE) domains of NRPS and PKS gene clusters have been utilized as enzymes for macrolactone formation to produce a wide range of natural/non-natural macrocyclic compounds [58][59][60][61][62][63

• categorized into three distinct classifications based on the type of enzymatic conversions: 1) regio- and stereoselective late-stage functionalization of core scaffolds, 2) in situ generation of highly reactive intermediates, and 3) one-step construction of macrocyclic or fused multicyclic scaffolds. This

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• modifications have been observed during the maturation of different RiPPs. One example is the biosynthesis of thiopeptide GE2270, which is produced by the actinomycete Planobispora rosea ATCC53733 as a complex of related metabolites that differ in the number of methyl groups installed on the macrocyclic core

• aspartimide intermediates (Figure 6). The activity of most PAMTs depends on a cyclised precursor peptide. Modification of the aspartate/isoaspartate residue was found only in a hairpin-like or the macrocyclic region [71][78]. The underlying purpose of this structural requirement of PAMTs has not yet been

Diameter-selective extraction of single-walled carbon nanotubes by interlocking with Cu-tethered square nanobrackets

• Guoqing Cheng and
• Naoki Komatsu

Beilstein J. Org. Chem. 2024, 20, 1298–1307, doi:10.3762/bjoc.20.113

• Guoqing Cheng Naoki Komatsu Graduate School of Human and Environmental Studies, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan 10.3762/bjoc.20.113 Abstract We have been working with carbon nanotube separation through host–guest chemistry. Herein, a new macrocyclic host molecule, Cu-tethered

• , recently, a rigid metal-tethered macrocyclic host molecule “M-nanobrackets” (M = Cu, Co and Pd) [11]. While the concept of the mechanically interlocked carbon nanotubes (MINTs) has been established by Pérez and López [12][13], Cu-tethered tetragonal nanobrackets 1a not only interlocked SWNTs, but also

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

• Koki Ikemoto Hiroyuki Isobe Department of Chemistry, The University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan 10.3762/bjoc.20.103 Abstract Cyclo-meta-phenylenes doped with nitrogen atoms at the periphery were designed and synthesized. The syntheses of the macrocyclic structures were

• nitrogen-doped [n]CMPs (3) containing outward-radiating nitrogen dopants. The properties and structures were investigated with UV–vis spectroscopy and X-ray crystallography, which revealed the fundamental properties of the nitrogen dopants in the macrocyclic structures. Results and Discussion Nitrogen

• structural features of nitrogen-doped [n]CMPs. The crystal molecular structures of 3a and 3b are shown in Figure 3. The hexagonal macrocyclic structure of 3a showed a chair-like conformation with alternating biaryl dihedral angles showing +/– values. The octagonal structure of 3b exhibited a saddle-like

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• terpenoids. LcTPS2 from Leucosceptrum canum was characterized as a versatile TS that generated six macrocyclic sesterterpenoids (11–16) and two macrocyclic diterpenoids (17,18), representing the first macrocyclic terpenoids isolated from plants (Table 1, Figure 2) [19]. In addition to linear prenyl

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• , achieving 52.5% higher production than controls without pH shock [67]. Conversely, the present authors were able to increase the production of antarlides, which have a 22-membered ring macrocyclic structure, by adding disodium hydrogen phosphate to the culture medium of Streptomyces sp. BB47 to prevent the

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

• .20.66 Abstract Chemoenzymatic strategies that combine synthetic and enzymatic transformations offer efficient approaches to yield target molecules, which have been increasingly employed in the synthesis of bioactive natural products. In the biosynthesis of macrocyclic nonribosomal peptides, polyketides

• for these natural products that aim to address the common issues in classical synthetic approaches and increase synthetic efficiencies, which have the potential to facilitate further pharmaceutical research. Keywords: biosynthesis; chemoenzymatic synthesis; macrocyclic peptides; macrocyclic

• increase the ratio of intramolecular nucleophilic attack, resulting in macrocyclic products via preorganization of substrate and enzyme in an active conformation [17][18]. Chemoenzymatic strategies, which merge practical enzymatic transformations with modern organic synthetic methods to increase the

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

• solution. This concept was further developed with a bis-acridinium cyclophane [31] as a multiresponsive receptor for selective phase transfer. In organic media, this macrocyclic receptor presented an affinity for polyaromatic guests with strong selectivity for perylene. A reversible guest release was

• macrocyclic units. As shown previously, the tweezers adopt an open “W” form that can be switched to a closed “U” form by Zn2+ complexation. However, in this system, depending on the zinc counter ions either a bis(terpy) 2:1 complex or a 1:1 complex is obtained (Figure 11). With non-coordinating triflate

Multi-redox indenofluorene chromophores incorporating dithiafulvene donor and ene/enediyne acceptor units

• Christina Schøttler,
• Kasper Lund-Rasmussen,
• Line Broløs,
• Philip Vinterberg,
• Ema Bazikova,
• Viktor B. R. Pedersen and
• Mogens Brøndsted Nielsen

Beilstein J. Org. Chem. 2024, 20, 59–73, doi:10.3762/bjoc.20.8

• the terminal alkynes afforded the macrocyclic DTF-IF-RA scaffold 23. Molecular sieves (4 Å) were added to the reaction mixture as this has previously been shown to significantly promote the Glaser–Hay coupling [28]. Compounds 20 and 21 were unfortunately very sensitive compounds that were found to

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• (Figure 1C). Elongation of the tether in fullerenes 10 and 11 reduced product ratios to still significant A/D10/9 ~ A/D11/9 = 2.1. The origin of this decrease in anion–π catalysis is likely to include increasing entropy losses in pseudo-macrocyclic transition states. Normalized against the fullerene-free

• pseudo-macrocyclic transition states, bound non-covalently to both the active π surface and the ammonium cation of the tether. Normalized against the fullerene-free control 20, the most preorganized dyad 21 gave a new record A/D21/20 = 4.1. This value was much higher than the previous best A/D8/9 = 2.6

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

• , 29.2, 23.7 ppm; HRESI(+)-MS (m/z): [M + H]+ calcd for C140H171N10O15: 2233.2953; found, 2233.2883. a. Active-metal template (reported in the literature) and b. active-metal template clipping (used in this work) methods. Macrocyclic components of the [2]rotaxanes. Top: HRESI(+)-MS spectrum of the

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• advantages for tailoring new catalysts to specific reactions and optimize selectivity [22][27]. Cobalt catalysts successfully employed in CO2 reduction are mainly based on macrocyclic ligands, such as tetraazacyclodecene and its derivatives [3][28][29], porphyrins [30][31][32][33][34], or phthalocyanines [35

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• deviation of 0.054 Å from the mean-square plane. The nuclear-independent chemical shift (NICS) [48][49][50] values of 5 in its optimized conformation were used as a magnetic criterion of aromaticity. The NICS(0) value for the macrocyclic ring (+2.23 ppm in DMSO), calculated at the HF/6-31+G(d) level, shows

• ]. Moreover, the size of internal cavity formed by the nitrogen atoms N5, N8, N13, and N16 (≈2.6 Å × 2.8 Å according to the DFT calculations) enables to chelate various metal cations. Herein, we attempted to prepare compounds 11 and 12 by annulation of two 1,2,4-triazole rings onto the macrocyclic core of 5

• macrocyclic derivatives (e.g., 12) were formed from 5 under reflux in AcOH for 7 h. The only isolated product was pyrazolopyrimidine 14 (38%) whose structure was assigned based on NMR and HRMS (ESI+) data. It should be noted that all signals in the 1H and 13C NMR spectra of 14 in DMSO-d6 except N–CH3 and C3–H

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

• metals. In this perspective article, the overview of both the early designs of porphyrin-crown ether hybrids, as well as the most recent advances in the synthesis and characterisation of this remarkable group of macrocyclic systems, are addressed. The discussion covers the strategies employed in

• the possible future directions. Keywords: crown ethers; porphyrinoids; self-assembly; sensors; supramolecular chemistry; Introduction Many areas of modern supramolecular chemistry, organic, inorganic, materials and coordination chemistry, are based upon macrocyclic compounds of specifically-designed

• structures and tailored functions [1][2][3]. The design of novel macrocyclic compounds has laid the ground for phenomenal developments constituting supramolecular chemistry as a branch of chemical sciences. These fundamental developments included the discovery of crown ethers by Pedersen [4], followed by the

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• Waldemar Iwanek Bydgoszcz University of Science and Technology, Faculty of Chemical Technology and Engineering, Seminaryjna 3, 85-326 Bydgoszcz, Poland 10.3762/bjoc.19.109 Abstract Resorcin[4]arenes (R[4]A) are macrocyclic compounds with a cavity structure. Despite a relatively small cavity

• ; Introduction Resorcin[4]arenes are macrocyclic compounds with a cavity structure formed from resorcinol and aldehydes [1]. Of particular significance is their crown conformation, which stems from the presence of 8 hydroxy groups on the upper rim and a hydrophobic cavity [2]. This property plays an important

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• functionalization via the canonical organometallic steps of oxidative addition/reductive elimination was ruled out via catalytic reaction of the macrocyclic Groves-type porphyrin catalyst V, a species that is unable to accommodate the mutual cis-orientation of ligands for metal-centered reductive elimination. The

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

• , and catalysis [2][5][12]. Molecular encapsulation is not the only application area for these macrocyclic components at present. CDs are versatile molecules. Their 3D structure makes them exceptional building blocks for the design of innovative supramolecular architectures due to the differential

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

• rotation rate of the threads by a light-driven exchange between geometric isomers of a rotaxane scaffold; and (ii) a macroscopic bending of the crystalline array by a photo-triggered dimerization reaction of two identical linear components within the macrocyclic counterpart. Thus, in all the discussed

A fluorescent probe for detection of Hg²⁺ ions constructed by tetramethyl cucurbit[6]uril and 1,2-bis(4-pyridyl)ethene

• Xiaoqian Chen,
• Naqin Yang,
• Yue Ma,
• Xinan Yang and
• Peihua Ma

Beilstein J. Org. Chem. 2023, 19, 864–872, doi:10.3762/bjoc.19.63

• Xiaoqian Chen Naqin Yang Yue Ma Xinan Yang Peihua Ma Key Laboratory of Macrocyclic and Supramolecular Chemistry of Guizhou Province, Guizhou University, Guiyang 550025, China Guiyang College of Humanities and Science, Guiyang 550025, China 10.3762/bjoc.19.63 Abstract In this paper, tetramethyl

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• chemical synthesis of macrocyclic lactones which are the key structural motifs in some biologically active compounds, 14-methyl-2-phenoxy-1-oxa-2-phosphacyclotetradecane 2-oxide (74) was synthesized as the hapten from phenyl hydrogen (12-hydroxytridecyl)phosphonate (73) via Mitsunobu reaction. The

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