(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• activity, if not an improvement [1]. Often-used bioisosteres include the tetrazole group for a carboxylic acid [2][3][4][5] and fluorine atoms in place of hydrogens [6][7]. The inclusion of fluorine can alter the polarity of a molecule and can also be used to prevent epimerisation, as seen in

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• skeletal rearrangement (vide infra). Inclusion of the soft-nucleophile allyltrimethylsilane in the reaction of 10b to trap potential oxocarbenium ion intermediates also resulted in a complex mixture. During the isolation of the chloroalkyl ether products 11a–f, it was apparent that hydrolysis occurred

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• Hyg17 sequences with other members of the oxidoreductase family and inositol dehydrogenases and discuss specialized genome mining approaches using these sequences to identify new natural product biosynthetic clusters. Results and Discussion Hyg17 enzyme activity We found that Hyg17 formed inclusion

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• between the most stable calculated structure 1 and the crystalline structure is likely due to crystal packing forces, the presence of the counterion, and the inclusion of solvent molecules. The interfacial distances between the nearest neighbor centroid of a paraphenylene unit of [10]CPP and [5]CPP were

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

• dispersion forces and hydrogen bonding between the cyclodextrin (CD) unit and the guest molecule. Determination of the ee of chiral guests was achieved by observing the splitting of 1H NMR signals of the achiral host upon formation of diastereomeric inclusion complexes [18][19]. Shifting the H-3 and H-5

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

• , arylation, hydroxypropylation, amination, etherification, etc.) giving rise to synthetic CD derivatives with greater water solubility [2]. Thanks to their unique structure, CDs can offer exclusive advantages by allowing the entrapment of lipophilic molecules inside their inner cavities. This inclusion

• between HP-β-CD and DPPC rather than with CHOL which explains the obtained results. As for SBE-β-CD, it was reported that charged CDs could not interact with CHOL molecules and form inclusion complexes due to charge repulsion [26]. This could explain the results obtained for these two CDs. Hence, HP-β-CD

• ) was able to form two types of soluble complexes, with molar ratios of 1:1 and 1:2 (CHOL/DOM-β-CD). The latter (1:2 inclusion complex) occurred much more easily than that of the 1:1 complex showing a much higher equilibrium constant. At low CDs concentration, the formation of the 1:1 inclusion complex

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

• high yields from their respective acids, a result incompatible with a carbocation RPC mechanism. This Kochi decarboxylative chlorination separated itself from other pioneering methods of decarboxylative functionalization (i.e., Barton and Hunsdiecker) because of its inclusion of RLT as a key element of

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

• split over two positions yielding in total 5.75 mol of water per CO2. The hydration is similar to that of native α-CD [13] and that of the krypton inclusion complex which has 5.28 water/Kr [14]. The CO2 molecule refines with an optimal occupancy of 0.84 and linear geometry (178.2(6)o) with C–O bond

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

• containing CDs. Three clinical trials have demonstrated the use of CDs in the treatment of COVID-19. Two of them use the sulfobutyl ether β-CD/remdesivir inclusion complex and the third applies the α-CD/sulforaphane inclusion complex called Sulforadex® [6]. The approved Janssen vaccine against SARS-CoV-2

• use of CDs and further stimulate their market. The exploration of the potential of inclusion complexation is not limited to the biomedical field. CDs are renewable and biodegradable materials that enable green and environmental biotechnologies for all applications [11]. The ability of CDs to act as

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

• that TMeQ[6] and G form an inclusion complex with a host–guest ratio of 1:1 and the equilibrium association constant (Ka) was 2.494 × 104 M−1. The G@TMeQ[6] fluorescent probe can sensitively recognize Hg2+ ions by fluorescence enhancement. The linear range is 0.33 × 10−5–1.65 × 10−5 mol·L−1, R2

• form various host–guest inclusion complexes [16][17][18][19][20], which have broad application prospects in supramolecular catalysis [21][22][23], molecular recognition [24][25], and drug delivery [26][27]. In recent years, in the field of supramolecular chemistry, the detection of analytes based on

• TMeQ[6], and the wavelength redshifts from 301 nm to 330 nm, indicating that TMeQ[6] has binding affinity for G. The molar ratio method (Figure 2b) shows that when n(TMeQ[6])/n(G) = 1:1, the absorption value of the system gradually stabilizes, indicating that the guest G and TMeQ[6] form an inclusion

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

• value when the concentration of CS-TPE-2% was 48 µg/mL, where a simple inclusion complex formed between TBTQ-C6 and CS-TPE-2%. As a result, the optimal mixing ratio for the formation of TBTQ-C6/CS-TPE-2% supra-amphiphilic assembly is 0.10 mM TBTQ-C6 + 48 µg/mL CS-TPE-2%. Analogously, the optimal mixing

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• well as monomers for materials science [9][10][11][12][13][14][15]. In this context, their functionalization is fundamental to further improve their inclusion in fine organic synthesis and industrial processes. For this reason, in recent years, innovative protocols for the formation of new bonds on

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

• 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

• compounds [5]. The resulting supramolecular inclusion complexes provide enhanced water solubility and bioavailability/bioaccessibility of the nanoencapsulated bioactive compounds, higher oxidative and thermal stability or photostability of labile compounds, and their controlled release [6][7]. Vegetable oil

• the co-precipitation from a saturated solution. The peony oil content in the complex was almost 26%, with a high ratio of unsaturated FA glycerides of ≈90% [20]. In a very recent study, perilla (Perilla frutescens (L.) Britton) seed oil was complexed by γ-CD and the inclusion complex was used for

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

• 126, it was used to form water-soluble porphyrin nanospheres by self-inclusion complex formation in water. Tritriazole-bridged porphyrin system This section contains the synthesis of porphyrin conjugates having three 1,2,3-triazole groups as linkers. In 2012, Beletskaya and co-workers [55] described

• . Furthermore, these two structurally similar porphyrins 166a,b were used as hosts for the intermolecular formation of inclusion complexes with tetrasodium tetraphenylporphyrintetrasulfonate 132 in aqueous solution, leading to the constructions of two different nanoarchitectures with alternating porphyrin and

• , Jayawickramarajah and co-workers [69] synthesized a water-soluble porphyrin-fullerene (C60) nanorod through the formation of an inclusion complex between an octa(permethylated-β-CD)-Zn-porphyrin 174 and a pristine C60. For the construction of the nanorod, porphyrin 174 was first obtained in 65% yield by a Cu(I

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

• in about 30% yield (for β-CD) [6][7]. The C-6 regioselectivity can be attributed to the inclusion of pyridine into the CD cavity in such a way that it activates only the hydroxy groups on the primary side. Several alternative methods have been developed with the aim of further improving the yield of

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

• having hydrophobic cavities and hydrophilic exterior surfaces, CDs are widely used in the pharmaceutical field to form inclusion complexes mostly with nonpolar molecules in their cavities [22]. In addition, CDs also offer several advantages for colonic drug delivery, because CDs are broken down by the

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

• Max Petitjean Jose Ramon Isasi Department of Chemistry. University of Navarra. 31080 Pamplona, Spain 10.3762/bjoc.19.7 Abstract Cyclodextrins, cyclic oligosaccharides with a hydrophobic cavity that form inclusion complexes with nonpolar molecules, can be used to functionalize other

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• range of structural types than the trivalent compounds. A number of the compounds required inclusion of several conformational isomers, and for the cationic compounds, the counterions were included, and the experimental chemical shifts included compounds as pure liquids and as CDCl3, CH2Cl2, CH3CN, DMSO

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

• ingredients (APIs) is necessary to render them bioavailable. This study addresses the poor solubility of two potent steroid hormones, 17β-estradiol (BES) and progesterone (PRO), via their complexation with two water-soluble native cyclodextrins (CDs) namely β-CD and γ-CD. The hydrated inclusion complexes β

• host–guest stoichiometries and water contents of the four hydrated inclusion complexes enabled accurate assignment of the chemical formulae of these ternary systems. Predicted electron counts for the complexed molecules BES and PRO correlated reasonably well with the complex compositions indicated by

• pharmaceutical industry for many decades. However, the complexation of APIs with cyclodextrins (cyclic oligosaccharides) resulting in the formation of inclusion complexes, has proven to be a versatile technology for overcoming not only the poor aqueous solubility of APIs, but also unfavourable properties such as

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

• proof of the partial self-inclusion of the triazole into the internal space of CD is the fragment of the NOESY spectrum (Figure 1a), where the interaction of the triazole hydrogen with H–C6A, H–C5A, and H–C6 from the glucose unit next to the unit A is clearly seen indicating the interaction between the

• desymmetrization of the molecule caused by a partial and reversible self-inclusion of the triazole moiety into the CD cavity, as was previously studied in detail for the CD dimers prepared by CuAAC reaction [15]. Although such self-inclusion was not prominent for dimers based on the short propargyl ether linker

• 10 the same pattern of methyl splitting, though a much weaker one (Figure 2). We suppose that the chloroform where the spectrum of 9 was measured prevents the self-inclusion of the triazole ring. Concluding all the abovementioned, we may assume that a type of spacer between two CD parts in a dimer

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• products, warranting inclusion in current and future biodiscovery programs. Verongid sponges have been a prolific source of bioactive and novel bromotyrosine-derived alkaloids with more than 374 compounds currently reported [1]. Whilst this particular structure class includes a large number of simple

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• ][25][26]. These catalytic cross-coupling reactions tend to follow similar pathways to the Michaelis–Arbuzov reaction, with the inclusion of a catalytic intermediate step. A number of suitable catalysts have been identified, ranging from nickel(II) bromide and nickel(II) chloride, to palladium(II

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

• -workers [19] reported an efficient photocatalytic supramolecular system based on a self-assembled nanosystem. The self-assembled system was obtained in an aqueous medium by inclusion of ammonium benzoyl-ʟ-alaninate (G) in a tetraphenylethylene-embedded pillar[5]arene (m-TPEWP5). The resulting worm-like

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• hydrazone groups. The use of N-TAAD derivatives as potential ligands and receptors was showcased through forming boron chelates and host–guest complexes with water and simple alcohols. Keywords: azaadamantanes; cyclotrimerization; hydrazones; inclusion complexes; molecular recognition; Introduction

• and carbamate groups form inclusion complexes with water or methanol (Figure 3a–d). In the crystal state, a common hydrogen-bonded motif is observed, in which the guest molecule is located in a pocket created by amide/carbamate groups and the triazinane ring of the 3N-TAAD structure that is well

• ). Such symmetrization can be explained by a pre-organization of N-amido groups through the coordination of water/alcohol leading to the host–guest complex observed in the X-ray. The formation of the inclusion complexes H2O@TAADs 4a and MeOH@4c·H+ was additionally explored by DFT calculations at the

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• , apparently [88][89][90][91]. Concerning the definition of drug-like compounds, past the ground breaking Lipinski’s rule of five [92], defining more precise criteria for the inclusion of a given chemical, possibly dependent on the target considered, remains an interesting research subject [88][93][94][95][96

• for their synthesis were often due to preceding hit to lead research programs followed by their inclusion in chemical libraries. But there was also the more academic stance “we can reach these compounds with our new chemistry so let’s investigate its scope and prepare some derivatives”. And all this