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

Preparation of β-cyclodextrin/polysaccharide foams using saponin

• Max Petitjean and
• José Ramón Isasi

Beilstein J. Org. Chem. 2023, 19, 78–88, doi:10.3762/bjoc.19.7

• polysaccharides. Xanthan gum, locust bean gum or chitosan can be crosslinked using citric acid in the presence of β-cyclodextrin to produce insoluble matrices. In this work, polymeric foams based on those polysaccharides and saponin have been prepared using a green synthesis method to increase the porosity of the

• matrices. The saponin of soapbark (Quillaja saponaria) has been used to obtain foams using different procedures. The influence of the synthesis path on the porosity of the materials and their corresponding sorption capacities in the aqueous phase were evaluated. Keywords: chitosan; cyclodextrin polymers

• potential uses can be either for oral delivery targeting intestine [33] or for an anti-skin cancer treatment [35], for example. This complexation step is also interesting for the synthesis of molecular imprinted polymers containing cyclodextrin [36]. In previous works, we have produced crosslinked

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• : cyclodextrin; complexation; 17β-estradiol; progesterone; solubility; X-ray diffraction; Introduction The insolubility of active pharmaceutical ingredients (APIs) and other bioactive compounds in aqueous media and the associated challenges for effective drug delivery are well known to have beleaguered the

• their chemical instability, adverse side effects such as gastrointestinal irritation, and unpleasant tastes and odours [1][2][3][4][5]. Here we report an investigation of the cyclodextrin (CD) inclusion of two notable bioactive compounds (Figure 1), namely the most potent human estrogen, 17β-estradiol

• ,) with purity >98% and progesterone (C21H30O2) with purity >98% were purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany). β-Cyclodextrin (β-CD; C42H70O35) with purity >98% and water content 13.7(1)% (n = 2) was purchased from Cyclolab (Budapest, Hungary), while γ-cyclodextrin (γ-CD; C48H80O40

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• , 162 06 Prague, Czech Republic 10.3762/bjoc.18.170 Abstract A series of β-cyclodextrin dimers selectively permethylated on the primary or secondary rim with two different types of spacers have been synthesized effectively utilizing conventional and newly developed methods. Their structure analyses by

• better effectiveness than other tested supramolecular hosts. Keywords: cyclodextrin; dimer; methylation; solubilization; tetracene; Introduction Cyclodextrins (CDs) are cyclic oligomers of glucose that play an important role in supramolecular chemistry [1]. The structure of any CD contains a

• pentacene and other larger linear acenes if we would achieve some success with it. In this work, we report on the efficient synthesis of new cyclodextrin supramolecular hosts based on selectively methylated β-CD derivatives and their dimers; moreover, we compare their effectiveness in the solubilization of

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• Naser-Abdul Yousefi Morten L. Zimmermann Mikael Bols Department of chemistry, University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark 10.3762/bjoc.18.165 Abstract An α-cyclodextrin protected with 2,4-dichlorobenzyl groups on the primary alcohols and ordinary benzyl groups on the

• ; cyclodextrin; debenzylation; 2,4-dichlorobenzyl; selective; Introduction α-Cyclodextrin (1) is a cyclic carbohydrate consisting of six α-1,4-linked ᴅ-glucose molecules (Figure 1). It has a donut-like structure with the glucose residues all aligned with the α-side towards the center of the ring and the polar

• electron-poor benzyl groups reacting much more sluggishly. Indeed the per-2,4-dichlorobenzyl (DCB) protected compound 1 was completely resistant to DIBAL even when treated for several days [15]. This led us to wonder if an α-cyclodextrin protected on the primary hydroxy groups with DCB groups and on the

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

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• ), Dunkerque, France 10.3762/bjoc.18.140 Abstract A simple method for the preparation of β-cyclodextrin derivatives containing covalently bonded aldehydes via an imine bond was developed and used to prepare a series of derivatives from 6I-amino-6I-deoxy-β-cyclodextrin and the following volatile aldehydes

• benzaldehyde) and static headspace-gas chromatography (for benzaldehyde, heptanal, and 5-methylfurfural). The aldehyde release rate from the imine was shown to depend substantially on the pH from the solution and the air humidity from the solid state. Keywords: aldehyde; controlled release; cyclodextrin

• , we describe the synthesis of ten pro-fragrances – Schiff bases prepared from amino-β-cyclodextrin and common volatile aldehydes. Aldehydes constitute a prominent class of molecules broadly used as food product additives and are also key components of perfumes [24]. They were therefore chosen as an