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

• ). Having established the method, we chose various cyclic compounds (noradamantane, adamantane, cyclohexane derivatives) with desired symmetry and measured NMR spectra of these guest molecules (2–8) in α-cyclodextrin and cyclodextrins with a larger cavity (β-CD and γ-CD, Figure 4). In all cases, the 1H NMR

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

• potential of RLT reactions to be rapid and efficient. In both cases, benzylic carboxylic acids were most amenable as substrates, with alkyl carboxylic acids such as adamantane and dicyclohexylmethane providing fluorinated aliphatic products in low to moderate yields. Asymmetric RLT catalysis has also been

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

• interaction was observed. In 2010, the same group also reported the construction of a well-defined porphyrin nanowire [70] in water using Zn(II) porphyrin-CD conjugate 174 and free-base porphyrin-adamantane conjugate 176b through a robust 1:1 β-CD/adamantane host–guest interaction. First, porphyrin 176b was

• porphyrin 174 and stirred at room temperature for 24 h, solubilization occurred, resulting in a homogeneous solution. This is due to the formation of a supramolecular assembly in which the hydrophobic adamantane arms of 176b are sequestered by the β-CD arms of porphyrin 174, resulting in water solubility

• -tetratriazole-linked porphyrin-BODIPY conjugate 164. Synthesis of meso-tetratriazole-linked porphyrin-β-CD conjugates 166a,b. Synthesis of tetratriazole-bridged meso-arylporphyrins 171a–c and 172a–c. Synthesis of octatriazole-bridged porphyrin-β-CD conjugate 174 and porphyrin-adamantane conjugates 176a,b

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

• , the central scaffold should also have a rigid geometry without much conformational flexibility to create a preorganized binding pocket. In this regard, the adamantane scaffold received some attention as it represents a conformationally strained analog of the cyclohexane ring [10][11][12][13]. However

• derivatives involves the intramolecular cyclotrimerization of C=N bonds in a suitable trisimine precursor (Scheme 1). Previously, 3O-TAADs 2 were prepared by cyclization of corresponding trisoximes 1 [21]. However, this reaction is slow and reversible (upon heating adamantane structure 2 reverts to the tris

• equilibrium to the adamantane form by forming a stable boronate adduct 18 having a diamantane structure through the reaction with phenylboronic acid. Note that product 18 contains an unprecedented 2,4-dioxa-1,5,7,10-tetraaza-3-boraadamantane motif (Scheme 4). This result demonstrates that N-amino-substituted

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• as guest molecules. Here we report the co-crystal structures of phenol, which is solid at room temperature, with both 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane (TDA) and 1,3,5,7-tetrakis(2,4-diethoxyphenyl)adamantane (TEO). The co-crystals were obtained from solutions in dichloromethane by slow

• . The encapsulation occurs even though the host compound assembling into the crystal lattice is able to also crystallize in solvate-free form [12]. Three tetraaryladamantanes (TAAs) were found to show this behavior as hosts, namely 1,3,5,7-tetrakis(2,4-dimethoxyphenyl)adamantane (TDA), 1,3,5,7-tetrakis

• (2,4-diethoxyphenyl)adamantane (TEO), and 1,3,5,7-tetrakis(2-bromo-4-methoxyphenyl)adamantane (TBro). The X-ray crystal structures of over 100 EnOCs have been reported thus far [13][14][15][16], including structures with chiral guests that allow for the determination of the absolute [17] or relative

Manganese/bipyridine-catalyzed non-directed C(sp³)–H bromination using NBS and TMSN₃

• Kumar Sneh,
• Takeru Torigoe and
• Yoichiro Kuninobu

Beilstein J. Org. Chem. 2021, 17, 885–890, doi:10.3762/bjoc.17.74

• . The reaction of adamantane (1h) proceeded selectively at the tertiary C(sp3)–H bond to give a mixture of mono- and dibrominated products (2h and 2h′). The selectivity of 2h and 2h′ can be controlled by varying the reaction time; mono-brominated 2h was obtained in 62% yield as the major product after

• 30 min of reaction and dibrominated 2h′ was afforded as the major product after 18 h. Similarly, 1,3-dimethyladamantane (1i) and methyl adamantane-1-carboxylate (1j) were successfully converted to brominated products 2i and 2j, respectively. For benzeneacetic acid methyl esters 1k, 1l and 1m, the C

A new method for the synthesis of diamantane by hydroisomerization of binor-S on treatment with sulfuric acid

• Rishat I. Aminov and
• Ravil I. Khusnutdinov

Beilstein J. Org. Chem. 2020, 16, 2534–2539, doi:10.3762/bjoc.16.205

• hydrocarbons and show peculiar chemical behavior. Crude oil is known to be the main natural source of diamondoids. In the oil and gas field exploration, the presence of diamondoids is used to evaluate the field maturity. Whereas the synthesis and chemical reactivity of adamantane, the first member of the

[3 + 2] Cycloaddition with photogenerated azomethine ylides in β-cyclodextrin

• Margareta Sohora,
• Leo Mandić and
• Nikola Basarić

Beilstein J. Org. Chem. 2020, 16, 1296–1304, doi:10.3762/bjoc.16.110

• decarboxylation and [3 + 2] cycloaddition take place in the ternary complex, whereas such a reactivity from bulky adamantane 3 is less likely. This proof of principle that decarboxylation and cycloaddition can be performed in the β-CD cavity has a significant importance for the design of new supramolecular

• with β-CD (4-amino-N-cyclohexylphthalimide, K = 6200 M−1) [50]. An analogous titration in CD3CN/D2O (3:7 v/v) was also conducted for 3 with β-CD. The addition of β-CD to the solution of 3 induced downfield shifts of the signal corresponding to the adamantane 6 position and the phthalimide signals

• ). However, the approximated association constant for 3@β-CD, K = 2600 ± 600 M−1, is similar to the known association constants for different adamantane derivatives with β-CD (K = 103–105 M−1) [52], in agreement with the anticipated good fit of the adamantane moiety in 3 to the β-CD cavity. After

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• compounds and the reference drugs. Then, the normalized PMI ratios were plotted on a triangular graph where the vertices (0,1), (0.5,0.5), and (1,1) represent a perfect rod (i.e., 2-butyne), disc (i.e., benzene), and sphere (i.e., adamantane), respectively (Figure 4). This analysis showed that all compounds

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• present the design, synthesis and biological evaluation of novel mannosylated desmuramyl peptide derivatives. Mannose was coupled to dipeptides containing a lipophilic adamantane on N- or C-terminus through a glycolyl or hydroxyisobutyryl linker. Adjuvant activities of synthesized compounds were

• investigated in the mouse model using ovalbumin as an antigen. Their activities were compared to the previously described mannosylated adamantane-containing desmuramyl peptide and peptidoglycan monomer. Tested compounds exhibited adjuvant activity and the strongest enhancement of IgG production was stimulated

• by compound 21 (Man-OCH2-ᴅ-(1-Ad)Gly-ʟ-Ala-ᴅ-isoGln). Keywords: adamantane; adjuvant activity; desmuramyl peptide; mannose; Introduction Dendritic cells capture and internalize invading pathogens. Pathogen-associated molecular patterns have been known for a long time to affect the immune system of

Metal-free mechanochemical oxidations in Ertalyte^® jars

• Andrea Porcheddu,
• Francesco Delogu,
• Lidia De Luca,
• Claudia Fattuoni and
• Evelina Colacino

Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

• reaction times (up to 1.5 h), did not lead to any significant improvement. However, we were pleased to find that the less hindered 2-aza-adamantane-N-oxyl (AZADO) was more effective than TEMPO in terms of conversion and yield with the model alcohol substrate, promoting an almost quantitative conversion of

• alcohols 6a and 7a under mechanochemical conditions and in the presence of KBr. Scope of secondary alcohols in the oxidation under mechanical activation conditions. aAll yields refer to isolated pure products. b2-Aza-adamantane-N-oxyl (AZADO, 2 mol %), 60 min. cOxidation carried out without AZADO catalyst

Selective benzylic C–H monooxygenation mediated by iodine oxides

• Kelsey B. LaMartina,
• Haley K. Kuck,
• Linda S. Oglesbee,
• Asma Al-Odaini and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2019, 15, 602–609, doi:10.3762/bjoc.15.55

• abstraction catalyst than the chlorine radical allowed for the more selective tertiary acetoxylation of adamantane [51]. Nitroxyl radicals formed from species such as NHPI are well studied H-atom abstraction catalysts often used in the functionalization of hydrocarbons [41]. Building upon the ability to

• selectively acetoxylate the tertiary position of adamantane, we sought to apply this approach to the selective acetoxylation of benzylic C–H bonds. As shown in Figure 1, the use of ammonium iodate in combination with an NHPI-type catalyst yielded efficient benzylic oxidation of n-butylbenzene (1a) to 1

Nucleofugal behavior of a β-shielded α-cyanovinyl carbanion

• Rudolf Knorr and
• Barbara Schmidt

Beilstein J. Org. Chem. 2018, 14, 3018–3024, doi:10.3762/bjoc.14.281

• cross-peaks to the adamantane protons); 13C NMR (CDCl3, 100.6 MHz) δ 25.9 (d, CH-5´), 26.5 (d, CH-7´), 28.8 (q, 2 × 1-CH3), 30.0 (q, 2 × 3-CH3), 32.9 (t, CH2-4´-/9´), 35.6 (t, CH2-8´-/10´), 37.0 (t, CH2-6´), 37.4 (d, CH-1´-/3´), 50.5 (quat, C-3), 51.5 (quat, C-1), 77.1 (quat, C-2´), 118.2 and 119.4 (2

Rational design of boron-dipyrromethene (BODIPY) reporter dyes for cucurbit[7]uril

• Mohammad A. Alnajjar,
• Jürgen Bartelmeß,
• Robert Hein,
• Pichandi Ashokkumar,
• Mohamed Nilam,
• Werner M. Nau,
• Knut Rurack and
• Andreas Hennig

Beilstein J. Org. Chem. 2018, 14, 1961–1971, doi:10.3762/bjoc.14.171

• used polymer microparticles with surface-bound CB7 [66] and added them to a solution containing a mixture of 5 and 1-(aminomethyl)adamantane (AMADA). The latter was added to reduce the surface group density of the dye and prevent undesired self-quenching at high surface concentrations of the

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• natural compounds is a widely used approach in medicinal chemistry [1]. The increased lipophilicity of adamantane-containing compounds compared with non-adamantylated derivatives [2] leads to considerably higher solubility of these compounds in blood plasma and their easier penetration through cell

• membranes. The conjugation of adamantane with heterocyclic compounds also provides a method to modify the pharmacological profile and frequently leads to a new type of bioactivity. For example, N-adamantyl tetrazoles 1 and 2 (Figure 1A) demonstrate lower toxicity and, simultaneously, more potent activity

• heterocycles 5 and 6 using well-established 1H and 13C NMR methods (such as 1D, 2D COSY, HMQC, HMBC, and INADEQUATE spectra) was difficult because the heterocyclic moiety was covalently attached to the adamantane tertiary carbon that had no bound hydrogen atoms. Nuclear Overhauser effect spectroscopy (NOESY or

Superstructures with cyclodextrins: Chemistry and applications IV

• Gerhard Wenz

Beilstein J. Org. Chem. 2017, 13, 2157–2159, doi:10.3762/bjoc.13.215

• insulin and lysozyme were also conjugated to the guest adamantane. The complexation of these conjugates by pegylated β-CD gives rise to superstructures which provide slow release and maintain full biological activity [21]. Significant progress was also achieved in the field of CD rotaxanes. A [3]-rotaxane

Molecular recognition of N-acetyltryptophan enantiomers by β-cyclodextrin

• Spyros D. Chatziefthimiou,
• Mario Inclán,
• Petros Giastas,
• Athanasios Papakyriakou,
• Konstantina Yannakopoulou and
• Irene M. Mavridis

Beilstein J. Org. Chem. 2017, 13, 1572–1582, doi:10.3762/bjoc.13.157

• )salicylaldimine complex in ethanol, novel association of β-CD monomers in structures of β-CD complexes, e.g., with 4-pyridinealdazine [30], polyethylene glycol [38] or adamantane [39]. Conclusion This work has been focused on the ability of β-CD to discriminate between the enantiomers of N-acetyltryptophan. NMR

Interactions between shape-persistent macromolecules as probed by AFM

• Johanna Blass,
• Jessica Brunke,
• Franziska Emmerich,
• Cédric Przybylski,
• Vasil M. Garamus,
• Artem Feoktystov,
• Roland Bennewitz,
• Gerhard Wenz and
• Marcel Albrecht

Beilstein J. Org. Chem. 2017, 13, 938–951, doi:10.3762/bjoc.13.95

• investigation of cooperativity of multiple host–guest interactions using AFM has been reported by several groups [40][41][42][43][44][45]. Huskens and co-workers measured the supramolecular interactions between a β-CD-modified planar surface and mono-, di- and trivalent adamantane guest molecules attached to an

• , CD polymer and CD, and CD and CD at the tip and the planar surface, respectively, exerted by the adamantane ditopic connector molecules were systematically investigated. All four configurations are schematically depicted in Figure 2. Results and Discussion Synthesis of the shape-persistent CD polymer

• hydrophilic guest to significantly improve the solubility in water. Binding constants of about 40,000 M−1, which were in the same range as literature values for the incorporation of adamantane derivatives into β-CD, [61] were obtained using ITC measurements considering a two-step sequential complexation with

A self-assembled cyclodextrin nanocarrier for photoreactive squaraine

• Ulrike Kauscher and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2016, 12, 2535–2542, doi:10.3762/bjoc.12.248

• significant potential for photodynamic therapy. Herein we report that squaraines can be immobilized on a self-assembled nanocarrier composed of amphiphilic cyclodextrins to enhance their photochemical activity. To this end, a squaraine was equipped with two adamantane moieties that act as anchors for the

• aqueous solution of the vesicle [30]. The hydrophobic cyclodextrin cavities are well known to form size-selective inclusion complexes with apolar compounds such as adamantane [31]. In several publications, we have shown that CDVs retain this ability by keeping the cavity available for host–guest

• squaraines can also be immobilized onto CDVs. For this purpose, the squaraines are equipped with two adamantane functions that bind into the cavities of cyclodextrin on the surface of the CDVs (Figure 1). The resulting divalent host–guest interaction should lead to a higher binding affinity of the squaraine

Diradical reaction mechanisms in [3 + 2]-cycloadditions of hetaryl thioketones with alkyl- or trimethylsilyl-substituted diazomethanes

• Grzegorz Mlostoń,
• Paulina Pipiak and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2016, 12, 716–724, doi:10.3762/bjoc.12.71

• -tetrasubstituted isomers exclusively. In other studies, performed with cycloaliphatic thioketones, e.g. with adamantane-2-thione or 2,2,4,4-tetramethyl-3-thioxocyclobutanone, the growing stability of the corresponding 1,3,4-thiadiazolines obtained in reactions with diazomethane, diazoethane, and 2-diazopropane was

Cupreines and cupreidines: an established class of bifunctional cinchona organocatalysts

• Laura A. Bryant,
• Rossana Fanelli and
• Alexander J. A. Cobb

Beilstein J. Org. Chem. 2016, 12, 429–443, doi:10.3762/bjoc.12.46

• oxidative coupling – initially between 3-methoxycatechol (100) and tert-butyl 1-oxoindan-2-carboxylate (101) using an adamantane derivative of cupreidine CPD-102 to give the corresponding adduct 103 in 84% yield and 81% ee (Scheme 24a) [69]. An attempt to develop this methodology towards an asymmetric total

Supramolecular structures based on regioisomers of cinnamyl-α-cyclodextrins – new media for capillary separation techniques

• Gabor Benkovics,
• Ondrej Hodek,
• Martina Havlikova,
• Zuzana Bosakova,
• Pavel Coufal,
• Milo Malanga,
• Eva Fenyvesi,
• Andras Darcsi,
• Szabolcs Beni and
• Jindrich Jindrich

Beilstein J. Org. Chem. 2016, 12, 97–109, doi:10.3762/bjoc.12.11

• as competitive host molecule to the aqueous solution of isomer 3 did not decrease significantly the aggregate size distribution, which indicates that α-CD is not able to inhibit the intermolecular interactions between the molecules of 3-O-Cin-α-CD. Potassium adamantane-1-carboxylate (AdCOOK) was a

Supramolecular polymer assembly in aqueous solution arising from cyclodextrin host–guest complexation

• Jie Wang,
• Zhiqiang Qiu,
• Yiming Wang,
• Li Li,
• Xuhong Guo,
• Duc-Truc Pham,
• Stephen F. Lincoln and
• Robert K. Prud’homme

Beilstein J. Org. Chem. 2016, 12, 50–72, doi:10.3762/bjoc.12.7

• octamethylene-linked β-CD dimer c (Figure 10a, b and c) [78] and related β-CD [79][80] dimers in aqueous solution. It was determined from ITC experiments that while β-CD formed a 1:1 host–guest complex with adamantane carboxylate, only one annulus of the β-CD dimer b and β-CD dimer c complexed adamantane

• )). Nevertheless, upon pressing the two halves together self-healing still occurs through β-CD substituent/adamantyl substituent complexation. Finally, if adamantane carboxylate is applied to one of the cut surfaces in sufficient quantity and the two halves are pressed together, competitive β-CD substituent

• /adamantane carboxylate complexation prevents self-healing ((c) and (e)). The properties of this hydrogel can also be utilized in controlling expansion and contraction and shape memory. The practical applications which potentially flow at the macroscopic level from such host–guest chemistry are substantial

Self-assemblies of γ-CDs with pentablock copolymers PMA-PPO-PEO-PPO-PMA and endcapping via atom transfer radical polymerization of 2-methacryloyloxyethyl phosphorylcholine

• Jing Lin,
• Tao Kong,
• Lin Ye,
• Ai-ying Zhang and
• Zeng-guo Feng

Beilstein J. Org. Chem. 2015, 11, 2267–2277, doi:10.3762/bjoc.11.247

• adamantane standard. Wide angle X-ray diffraction (WXRD) patterns were recorded on a Shimadzu XD-D1 X-ray diffractometer with Ni-filtered Cu Kα (1.54 Å) radiation (20 kV, 40 mA). Powder samples were scanned from 2θ = 4.5–60° at a speed of 5°/min. FTIR spectra were measured using a Shimadzu IR Prestige-21

Cholesterol lowering effects of mono-lactose-appended β-cyclodextrin in Niemann–Pick type C disease-like HepG2 cells

• Keiichi Motoyama,
• Yumi Hirai,
• Rena Nishiyama,
• Yuki Maeda,
• Taishi Higashi,
• Yoichi Ishitsuka,
• Yuki Kondo,
• Tetsumi Irie,
• Takumi Era and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2015, 11, 2079–2086, doi:10.3762/bjoc.11.224

• adamantane, which is often used as a guest molecule for β-CyD, using the quartz crystal microbalance method (QCM) in phosphate-buffered saline (PBS, pH 7.4) at 37 °C. As a result, the dissociation constant of Lac-β-CyD with adamantane was 9.8 × 10−7 M due to the potent complex formation. Therefore, this