Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• , affording 4 in 64% yield (Table 1, entry 2). However, at a higher concentration (0.5 g/L), a significant amount of starting compound 5 remained unconverted even after 4 days, and only 30% of 4 was isolated (Table 1, entry 3). To our delight, upon adding 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) [29] as the

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• -cyclodextrin [123]. An attempt was made to synthesize compound 3a in water under the reaction conditions specified in Table 1, entry 10. TLC analysis after 10 minutes revealed the presence of the starting nitrone in the reaction medium. The isolation of the product was achieved through extraction with EtOAc

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• isomerization (Figure 2) [29]. In 1997, Nakashima and co-workers reported the first rotaxane where the azobenzene was located on the axle, acting as a recognition site for a β-cyclodextrin macrocycle. Photoisomerization of the azobenzene controlled the shuttling of the macrocycle [30]. Later, Stoddart and co

• reported the first [3]rotaxane with three azobenzene units in the axle and two α-cyclodextrins as the macrocycle. The rotaxane was obtained as a single stereoisomer, where the two narrow rings of the cyclodextrin point to each other. Although no photoswitching studies were conducted, 1H NMR results showed

• include systems employing CBPQT4+ [43], cucurbit[7]uril [44], tetralactam [45], and pillar[5]arene [46]. Moreover, Qu and co-workers synthesized [2]rotaxanes with a biphenyl and an azobenzene acting as recognition units for an α-cyclodextrin macrocycle, which has two distinct fluorescent bulky groups as

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• known antidote that counteracts the effects of opioid overdose by interacting with the opioid receptor, whereas the γ-cyclodextrin derivative sugammadex (Figure 1) is an in vivo sequestrant for neuromuscular blocking agents rocuronium and vecuronium and blocks their action at the nicotinic acetylcholine

• that β-cyclodextrin (Figure 1)-based polymers could remove organic micropollutants from water [15][16]. For example, in 2021, Sessler and co-workers reported the synthesis of a calix[4]pyrrole (Figure 1)-based porous organic polymer, which exhibits the rapid uptake of dyes from water [17]. In addition

• , graphene functionalized with β-cyclodextrins [18], a starch-based β-cyclodextrin polymer [19], and pillar[5]arene-based crosslinked polymers have also been investigated as sequestrants for dyes [20]. The Isaacs group has a longstanding interest in the synthesis and mechanism of formation of macrocyclic

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• vesicles, micelles and nanoparticles, overcoming the difficulties in modifying cyclodextrin and cucurbituril. These features make CAs and PAs promising candidates for stimulus responsive drug release systems [46]. Their structural diversity and functional designability offer broad prospects for targeted

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• spontaneous complex formation between α-CD and tetrabromoaurate and its current status of use in a few mining sites in the United States. Keywords: bromoaurate; cyanoaurate; cyclodextrin inclusion; self-assembly; supramolecular interactions; Introduction Gold has allured and captivated humankind ever since

• sections of this review. The combination of interactions linking cyclodextrin channels with infinite polymer chains of tetrahaloaurate ions and their counterions affords a highly specific and stable superstructure that is the working pillar for the efficient and selective process of gold recovery from

• complex matrices such as ores and industrial waste. Review Isolating gold with α-cyclodextrin Process discovery and the role of self-assembly The discovery that α-CD could be used to isolate gold was made serendipitously [37]. A young researcher of the Stoddart group, Zhichang Liu, was trying to prepare

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• cyclodextrin) can promote enantioselectivity [76], although turnover from augmented macrocycles is not always achieved [26]. The affinity of generic hydrophobic pockets for a hydrophobic product often leads to product inhibition, since binding a single large product is entropically favored over binding two

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• cucurbituril [18], cyclodextrin [19], and calix[4]pyrrole [20], as well as flexible crown ethers [10][21]. Few two-dimensional (2D) shape-persistent macrocyclic compounds are used for this purpose. One difficulty in realizing 2D macrocycle-based orthogonal assembly is that the construction motif must be

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• challenge, cyclodextrin (CD) can be employed as a promising alternative owing to its low production cost. Thus, this study presents an overview of the precise synthesis of CD-based rotaxane and its application to polymers to simultaneously ensure inexpensive production and realize defined structures

• . Keywords: cyclodextrin; defined structure; precise synthesis; rotaxanes; stimuli-responsive material; Introduction Stimuli-responsive materials can satisfy the existing high demands on such materials owing to their multiple functionalities (e.g., for effective energy storage or as decomposables under mild

• maintaining a structural control that is as high as that in the small-molecule system, where complicated synthesis is more accepted. Employing cyclodextrin (CD) as a ring unit represents a reasonable option for reducing the synthetic cost because of its lower production cost compared with those of other

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

• of interactions (i.e., water–water and/or water–CD walls) contribute to the stability of the water assemble; (iv) how does the mechanism of the γ-CD hydration compare with those of its α-CD and β-CD counterparts. Keywords: cyclodextrin; DFT calculation; DSC/TG; hydration; thermodynamic

• ) that the number of "true" hydrating water molecules in the γ-CD pore is about 7. Effect of the addition of pre-formed water clusters (bulk binding) The stepwise binding of water molecules to the cyclodextrin host appears to be a favorable process. As indicated in our previous studies on α- and β-CDs

• in the cavity of the CD (with which the hydration reaction is thermodynamically favorable) is a particularly important result. Thermal dehydration of γ-CD γ-CD molecules in the crystal are stacked in such a pattern to form cage-type packing [24]. Both ends (rims) of the cyclodextrin cavity are closed

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• interaction interfaces with other proteins, nucleic acids, lipids, small molecules, and ions, starting from a protein structure. PeSTo-Carbs is specifically trained to predict carbohydrate and cyclodextrin binding interfaces on proteins. Two different modules are available: a general model PS-G for a wide

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• solvents (DES) [83]. Catalysis can also be achieved using molecular iodine [84], AlCl3 [85], sodium ascorbate [86], and even solid-state and nanoparticle-mediated catalysts like CuO/ZrO2 [87], Fe3O4@Si@MoO2 [88], caspacin-cyclodextrin functionalized magnetite nanoparticles (CPS CD) [89], and Mg-Fe

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

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• ]. It is important to note that we are not aware of any catalytic enantioselective hydrochlorination reactions of alkenes. Conjugate additions of HCl to a complex of α,β-unsaturated acids, incorporated in an α-cyclodextrin, which corresponds to a formal hydrochlorination was reported by Tanaka and co

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• solubility [14][15]. As early examples of the latter approach in the 1990s, Wennerström and co-workers reported the study of supramolecular BiCAP complexation of C60 with γ-cyclodextrin (γ-CD) [16]. Shinkai and co-workers synthesized water-soluble calixarene derivatives to form water-soluble complexes with

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• 2026/5, 121 16 Praha, Czech Republic Department of Inorganic Chemistry, Faculty of Science, Charles University, Hlavova 8, 128 43 Praha, Czech Republic 10.3762/bjoc.20.33 Abstract 13C NMR spectroscopic analyses of Cs symmetric guest molecules in the cyclodextrin host cavity, combined with molecular

• modelling and solid-state X-ray analysis, provides a detailed description of the spatial arrangement of cyclodextrin host–guest complexes in solution. The chiral cavity of the cyclodextrin molecule creates an anisotropic environment for the guest molecule resulting in a splitting of its prochiral carbon

• crystallization of host–guest complexes and their crystallographic analysis. Keywords: anisotropy; 13C NMR; cyclodextrin; host–guest complexes; Introduction Complexation of organic and inorganic compounds with α-, β-, or γ-cyclodextrins and their derivatives [1] is an established tool used in medicine for drug

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• encapsulated in the aqueous core of liposomes which is generally known as “drug-in-cyclodextrin-in-liposomes” (DCL) [6]. This novel delivery system has gained popularity in the past few decades and many publications proved its importance and significance. Actually, the use of the two delivery systems

• combined delivery system “drug-in-cyclodextrin-in-liposomes” (DCL) where CD–drug inclusion complexes are in contact with the membrane. The choice of CD in such a system does not only depend on the drug affinity towards the CD cavity, but should also take into consideration the affinity of the selected CD

• of the native CDs, their three-dimensional structure, and their dimensions (n = 6, 7, and 8 glucopyranose units for α-, β-, and γ-CD, respectively). This figure was reused by permission from Springer Nature from [21]. (“130 years of cyclodextrin discovery for health, food, agriculture, and the

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• low reactivity of these phthalimides, 10 mol % of catalyst was required. Cross-coupling reaction of sulfoximines 44 with N‑(arylthio)succinimides 1 catalyzed by a nanomaterial containing hexagonal boron nitride (h-BN) and γ-cyclodextrin-supported copper(II) acetate (h-BN@γ-CD@Cu(OAc)2) was developed

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• , are studied as potential CO2 capture agents due to their unique molecular structures and high selectivity towards CO2. In this paper we have investigated binding efficiency of a number of cyclodextrins towards CO2. It is found that the crystal structure of α-cyclodextrin with CO2 has a 1:1

• stoichioimetry and that a number of simple and modified cyclodextrins bind CO2 in water with a Kg of 0.18–1.2 bar−1 (7–35 M−1) with per-O-methyl α-cyclodextrin having the highest CO2 affinity. Keywords: carbon dioxide; crystals; cyclodextrin; gas binding; Introduction The concentration of carbon dioxide (CO2

• CO2 is captured by non-covalent binding. Henglein and Cramer showed many years ago that α-cyclodextrin (1, Figure 1), when treated with CO2 under pressure for several days gave crystals with the gas trapped inside [8]. According to Cramer only 1 was able to form crystals, while larger cyclodextrins

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ] demonstrated a mild and environmentally friendly biomimetic Clauson–Kaas synthesis of N-substituted pyrroles 37 through the reaction between various arylamines 36 and 2,5-DMTHF (2) using a sustainable catalyst β-cyclodextrin-SO3H in the nontoxic green solvent H2O without the formation of side products (Scheme

•  17a). In this protocol, cyclodextrin (CD) plays a dual role as an acid catalyst as well as a phase-transfer agent that facilitates the smooth conversion of reactants into products. Most importantly, this catalyst can be easily recovered and used again for up to five cycles (Figure 4), with almost no

• different areas of chemistry. Various pyrrole containing molecules. A tree-diagram showing various conventional and green protocols for Clauson-Kaas pyrrole synthesis. Reusability of catalyst γ-Fe2O3@SiO2-Sb-IL in six cycles. Recyclability of β-cyclodextrin-SO3H. Plausible mechanism for the formation of N

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• , Polytechnic University of Timişoara, Carol Telbisz 6, 30001 Timişoara, Romania 10.3762/bjoc.19.30 Abstract The goal of the study was the discrimination of β-cyclodextrin (β-CD)/hazelnut (Corylus avellana L.) oil/antioxidant ternary complexes through Fourier-transform infrared spectroscopy coupled with

• cheap method for the evaluation of quality and similarity/characteristics of these new types of cyclodextrin-based ternary complexes having enhanced properties and stability. Keywords: antioxidant; cyclodextrin; flavonoid; hazelnut vegetable oil; ternary supramolecular inclusion complex; Introduction

• –S23 and Tables S10–S12). Hypothetical interactions between the β-cyclodextrin host and guest molecules (flavonoid glycoside/flavonolignan and a fatty acid triglyceride from the hazelnut oil), not explicitly proven in this study. (a) Both triolein from hazelnut oil and hesperidin interact with β

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• triplet quenching pathways. The construction of water-soluble porphyrin nanospheres was reported by Zhang et al. in 2014 [54] by intramolecular host–guest interactions using porphyrin 126 containing two permethyl-β-cyclodextrin (PM-β-CD) and two dicarboxylatophenyl arms at meso-positions. The synthesis of

• presence of CuSO4 and sodium ascorbate in THF/H2O furnished the bis-triazole-bridged porphyrin-cyclodextrin conjugate 125 in 65% yield. Finally, porphyrin 126 was obtained from porphyrin 125 after ester hydrolysis with KOH and demetallation with concentrated HCl. After the successful synthesis of porphyrin

• from an amphiphilic 1,2,3-triazole-bridged porphyrin-permethyl-β-CD conjugates 131a,b was reported by Liu et al. [56] in 2015. First the porphyrin-cyclodextrin conjugates 131a,b were obtained in 90% and 70% yields, respectively, by the CuAAC click reaction between zinc(II) meso-tris(ethynylphenyl

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• of Science, Charles University, 128 43 Prague 2, Czech Republic 10.3762/bjoc.19.25 Abstract The first continuous flow method was developed for the synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin starting from native β-cyclodextrin through three reaction steps, such as monotosylation, azidation

• reduction steps were compatible to be coupled in one flow system obtaining 6-monoamino-6-monodeoxy-β-cyclodextrin in a high yield. Our flow method developed is safer and faster than the batch approaches. Keywords: azidation; continuous flow; β-cyclodextrin; H-cube; 6-monoamino-6-monodeoxy-β-cyclodextrin

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• amounts of β-cyclodextrin (β-CD) [81] under aqueous conditions at room temperature as well as under heating at 100 °C (entries 1 and 2, Table 1). Unfortunately, the model reactants remained unreacted and similar observations were recorded using a mixture of H2O/MeOH 1:4, and methanol as a reaction medium

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• in cancer-related deaths. With the current treatment possibilities, a definitive, safe, and effective treatment approach for CRC has not been presented yet. However, new drug delivery systems show promise in this field. Amphiphilic cyclodextrin-based nanocarriers are innovative and interesting

• , and furthermore in vivo antitumoral and antimetastatic efficacy in early and late-stage colon cancer models and biodistribution after single dose oral administration. This study was carried out to further elucidate oral camptothecin (CPT)-loaded amphiphilic cyclodextrin nanoparticles for the local

• -loaded polycationic-β-cyclodextrin nanoparticles caused reduced cell viability in CT26 and HT29 colon carcinoma spheroid tumors of mice and human origin, respectively. In addition, the release profile, which is one of the critical quality parameters in new drug delivery systems, was investigated