Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• antiproliferative activity of these acylphloroglucinols in HMEC-1 increases with increasing log P. Increasing the number of carbon atoms in the acyl group provides higher lipophilicity, which allows the compound to better penetrate across cellular membranes in the in vitro assay. In contrast, the activity of the

• stability and the inability of the compound to cross cellular membranes [66]. To prevent oxidation and improve its bioavailability, modifications of EGCG focus on synthesizing more stable analogs (Figure 7). Anderson et al. [67] replaced the hydrolytically labile ester bond with a more stable amine and

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

• Hale Ünal,
• Naile Öztürk and
• Erem Bilensoy

Beilstein J. Org. Chem. 2015, 11, 204–212, doi:10.3762/bjoc.11.22

• biological membranes through positive surface charge. Nanocapsules were evaluated for their in vitro characteristics such as particle size, zeta potential, drug loading and release profiles followed by cell culture studies with the MCF-7 and Caco-2 cell line evaluating their anticancer efficacy and

• nanocapsules were then coated with the cationic polymer chitosan to improve the cellular uptake and interaction with biological membranes and penetration through intestinal mucosa for absorption of CPT and reaching the circulation. Nanocapsules were characterized for their in vitro properties followed by cell

• uptake. Therefore the particle size should be in an optimum range which enables particles to diffuse and permeate through the biological membranes, but also should provide the maximum ability for encapsulation of drugs and sustained release. The influence of CD concentration, concentration of oil phase

Properties of cationic monosubstituted tetraalkylammonium cyclodextrin derivatives – their stability, complexation ability in solution or when deposited on solid anionic surface

• Martin Popr,
• Sergey K. Filippov,
• Nikolai Matushkin,
• Juraj Dian and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2015, 11, 192–199, doi:10.3762/bjoc.11.20

• acid [26]. Similar approaches of ionic self-assembly with CDs were used for the preparation of nanoparticles with external CD trigger [27], new material nanostructures [28], polyelectrolyte-surfactant complexes which yield new types of solid mesomorphous materials [29], or membranes with size-selective

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• drug permeability through biological membranes [9]. For instance, CDs and CD derivatives have been applied in both stabilization and solubility enhancement of CPT [10][11][12]. CD polymers are macromolecular structures bearing many CD moieties. This gives a number of advantages compared to native CDs

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• relatively rigid molecular and supramolecular systems. These systems mainly consist of peptides and proteins (e.g., scleroproteins, globular proteins, and membrane proteins), lipids (e.g., biological membranes), carbohydrates (e.g., cellulose) and nucleic acids (DNA, RNA). The impressive performance of the

• biological and artificial membranes [11][12][13], the utilization as spacer in FRET systems [14], and as building blocks in porous materials [15]. Although stiffness of the whole rod is desirable in many cases, a partial flexibility is often necessary. Especially for biological and biochemical applications

• , low ratios of 32a and α- or Me-β-CD, respectively, initially cause a slight decrease of the IM/IEX ratio (Figure 6, inset). The reason for this behavior remains still unclear. Recently we demonstrated that OSK rods are easily incorporated in biological membranes [11][12][13]. Because articulated rods

Effects of RAMEA-complexed polyunsaturated fatty acids on the response of human dendritic cells to inflammatory signals

• Éva Rajnavölgyi,
• Renáta Laczik,
• Viktor Kun,
• Lajos Szente and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 3152–3160, doi:10.3762/bjoc.10.332

• component of the phospholipid membranes found everywhere in the body [2]. Changes in the balance of n−3 and n−6 PUFAs in the diet upon low intake of n−3 PUFAs have been linked to several inflammation-related chronic diseases and certain mental illnesses [3]. Greenland Inuits with traditionally high seafood

Inclusion of trans-resveratrol in methylated cyclodextrins: synthesis and solid-state structures

• Lee Trollope,
• Dyanne L. Cruickshank,
• Terence Noonan,
• Susan A. Bourne,
• Milena Sorrenti,
• Laura Catenacci and
• Mino R. Caira

Beilstein J. Org. Chem. 2014, 10, 3136–3151, doi:10.3762/bjoc.10.331

• outcome of the experiment. We found that nylon filters remove RSV from the aqueous solution completely, allowing only some of the molecules which are protected by the CD to pass through the filter membrane. Of all the membranes tested the PTFE filters were found to give the most consistent results

Synthesis of uniform cyclodextrin thioethers to transport hydrophobic drugs

• Lisa F. Becker,
• Dennis H. Schwarz and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 2920–2927, doi:10.3762/bjoc.10.310

• either nearly insoluble in water or the binding constants are rather low [32][33][34]. We focussed our effort on the design of hydrophilic and/or amphiphilic CD thioethers, because only amphiphilic molecules can form [35][36] or incorporate into bilayer membranes [37][38]. Amphiphilic CD carriers can

Cyclodextrin–polysaccharide-based, in situ-gelled system for ocular antifungal delivery

• Anxo Fernández-Ferreiro,
• Noelia Fernández Bargiela,
• María Santiago Varela,
• Maria Gil Martínez,
• Maria Pardo,
• Antonio Piñeiro Ces,
• José Blanco Méndez,
• Miguel González Barcia,
• Maria Jesus Lamas and
• Francisco.J. Otero-Espinar

Beilstein J. Org. Chem. 2014, 10, 2903–2911, doi:10.3762/bjoc.10.308

• weight of 50–60 g, were incubated at 37.5 °C and a relative humidity of 62 ± 7.5% for 9 days in an incubator with an automatic rotating device. After removing the egg shell covering the air cell with an electric drill and cutting through the inner egg membranes, 0.3 mL of test substance was applied

• (fluconazole: 2 mg/mL, CDs: 10 mg/mL and final gel formulations: 0.65%, 0.75% and 0.82% gel with and without HPBCD) was applied onto the vasculated chorioallantoic membranes (CAM) of at least three eggs. The CAM, the blood vessels (including the capillary system), and the albumen were all observed over time

Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

• Kayoko Hayashida,
• Taishi Higashi,
• Daichi Kono,
• Keiichi Motoyama,
• Koki Wada and
• Hidetoshi Arima

Beilstein J. Org. Chem. 2014, 10, 2756–2764, doi:10.3762/bjoc.10.292

• , phospholipids and proteins of biological membranes in the higher concentration range. Thus, CDs are utilized for studying the functions of caveolae, lipid rafts, and cholesterol transporters in various fields of cell biology [5]. Interestingly, CDs can also form inclusion complexes with linear polymers. Harada

• disrupt LP by their interaction with lipid membranes. In particular, α-CD strongly interacts with phospholipids [5][39][40]. On the other hand, to prepare CD PPRXs, PEG should react with CDs in aqueous solution at high concentration of CDs. Thus, we should take particular care to prepare CD PPRXs of PEG

A green approach to the synthesis of novel phytosphingolipidyl β-cyclodextrin designed to interact with membranes

• Yong Miao,
• Florence Djedaïni-Pilard and
• Véronique Bonnet

Beilstein J. Org. Chem. 2014, 10, 2654–2657, doi:10.3762/bjoc.10.278

• enzymatic transesterification, sphingolipid myelin analogues bearing CD as polar heads were synthesized to interact with ceramids of brain membranes. Results and Discussion Insertion of the spacer A procedure for the preparation of compound 1 has already been described in previous articles [8]. The reaction

Encapsulation of biocides by cyclodextrins: toward synergistic effects against pathogens

• Véronique Nardello-Rataj and
• Loïc Leclercq

Beilstein J. Org. Chem. 2014, 10, 2603–2622, doi:10.3762/bjoc.10.273

• membrane charge induces the cell lysis. This mechanism is common for all ionic amphiphilic compounds and is well documented in the literature [66][67]. It is worth mentioning that the nonionic surfactants also act on membranes but their interaction mechanism is unknown. Some authors have proposed an

• interaction of the nonionic surfactants with lipid membranes by formation of channels through the membrane [68]. More recently, Groot and Rabone claimed that the inclusion of nonionic surfactants reduces the extensibility and the maximum stress that the bilayer can withstand [69]. These modifications bring

• consequence, the bacterial DNA replication is inhibited. Moreover, the bacterial cytoplasmic membranes can also be damaged leading to cell lysis [81]. In contrast to solutions of silver ions, the biocidal efficacy of the silver nanoparticles is improved because of a high specific surface-to-volume ratio

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• conditions in both compartments, giving a controlled supply of protons to the catholyte. Besides the implementation and maintenance costs of such a membrane, it also causes an elevated ohmic resistance between the electrodes decreasing the energy efficiency of the process. Moreover, most membranes have

• generated carboxylates, make the use of a membrane redundant, enabling the use of a simple undivided cell [44]. Moreover, the use of membranes in non-aqueous or aprotic environments is unsatisfactory as they become poorly conducting [44]. This procedure was patented and extended to various other substrates

Towards the sequence-specific multivalent molecular recognition of cyclodextrin oligomers

• Michael Kurlemann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 2428–2440, doi:10.3762/bjoc.10.253

• , such vesicles can be modified with bio-active ligands and serve as model systems to mimic biological processes on cell membranes [10][11]. In the field of materials science multivalency has been used to create functional polymers [12][13][14] and self-assembled electronic [15][16][17][18][19][20] or

A versatile δ-aminolevulinic acid (ΑLA)-cyclodextrin bimodal conjugate-prodrug for PDT applications with the help of intracellular chemistry

• Chrysie Aggelidou,
• Theodossis A. Theodossiou,
• Antonio Ricardo Gonçalves,
• Mariza Lampropoulou and
• Konstantina Yannakopoulou

Beilstein J. Org. Chem. 2014, 10, 2414–2420, doi:10.3762/bjoc.10.251

• wide β-CD opening available for inclusion of a hydrophobic guest molecule for intracellular transport, (ii) positively charged secondary and primary amino groups at physiological pH thus able to interact with negatively charged components of the cell membranes and achieve cell penetration [11] and (iii

• region. Finally the mass spectrum confirmed the identity of the product, which maintained an average molecular weight corresponding to ~3 δ-aminolevulinic acid moieties attached. Cell studies with 2: The capability of the conjugate to cross cell membranes and to produce PpIX intracellularly was examined

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

• Emma Werz and
• Helmut Rosemeyer

Beilstein J. Org. Chem. 2014, 10, 2307–2321, doi:10.3762/bjoc.10.240

• ability to form complex nano-architectures [5][6] as well as self-assembling aggregates such as micelles, vesicles [3] and bilayer formation of nucleolipids [7] offers numerous possibilities, e.g., for drug delivery [3]. Simultaneously, the interaction of such nanostructures with lipid membranes becomes

• paper which deals with the interaction of a defined oligonucleotide single strand, carrying nucleolipid head groups of different lipophilicity with lipid bilayer membranes, might be of importance for the optimization of the in vivo delivery of lipophilic siRNA [13] (e.g., by DNA trafficking as shown in

Expanding the scope of cyclopropene reporters for the detection of metabolically engineered glycoproteins by Diels–Alder reactions

• Anne-Katrin Späte,
• Verena F. Schart,
• Julia Häfner,
• Andrea Niederwieser,
• Thomas U. Mayer and
• Valentin Wittmann

Beilstein J. Org. Chem. 2014, 10, 2235–2242, doi:10.3762/bjoc.10.232

• centrifugation (5 min, 400g). The cells were lysed in lysis buffer (400 µL) containing Triton X-100 (0.5%) (for permeabilization of membranes and solubilization of proteins and to prevent aggregate formation), DNase (30 µg mL−1), RNase (30 µg mL−1), β-glycerophosphate (20 mM) (Ser/Thr phosphatase inhibitor

• nitrocellulose membranes (BioRad). Transfer efficiency was analyzed with Ponceau S staining. The membranes were blocked in milk (5% in PBS-T) for 1 h at rt, followed by incubation with anti-biotin antibody (Abnova, Anti-Biotin mAb clone SB58c, 1:2000 dilution in milk) at 4 °C overnight or anti-alpha-tubulin

• antibody (AA4.3, hypridoma supernatant in 1% FCS, 1:200 dilution in milk) for 1 h at rt. The membranes were washed (3 times, 10–15 min, PBS-T), incubated with secondary horseradish-peroxidase-conjugated anti-mouse antibody (Dianova, goat anti-mouse IgG (H+L)-HRP, 1:50000 dilution in milk, 1 h, rt), and

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• . These efforts include the development of liquid and solid absorbents and membranes [2][3][4][5][6][7]. Ionic liquids (ILs), which have attractive properties such as negligible vapor pressure, a wide liquid temperature ranges, good thermal stability, high ionic conductivity, and versatile solvation

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• films, liposomes, or membranes. Focal functionalization of dendrons can be performed prior to modification of the multivalent dendron periphery, or as postsynthetic modification. However, postsynthetic functionalization of the focal point of a rather bulky molecule is not necessarily facile owing to

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• and polymers offers a virtually unlimited number of encodings. In nature, carbohydrates are often linked to lipids, peptides or proteins. These conjugates are found inside cells, on cell membranes as well as in extracellular fluids and matrices. Surprisingly, the general understanding of the function

Automated solid-phase peptide synthesis to obtain therapeutic peptides

• Veronika Mäde,
• Sylvia Els-Heindl and
• Annette G. Beck-Sickinger

Beilstein J. Org. Chem. 2014, 10, 1197–1212, doi:10.3762/bjoc.10.118

• successively offers new targets for peptide drugs that classical small organic molecules cannot cover [3]. Although small synthetic drugs are in general orally applicable owing to their high metabolic stability, capable to cross cell membranes and small in size, which simplifies their production and costs

• , peptides are excreted by kidneys (renal clearance) or liver (hepatic clearance) within minutes [5][9]. Nevertheless, their ability to pass through membranes and the urgent need of alternative, more comfortable administration routes as the commonly used parenteral (subcutaneous, intramuscular and

• addition, SPPS can be carried out on cellulose papers, in which reagents are spotted onto porous membranes [65]. The typical reactions proceed only in the volume that has been infused into the solid pores. Again, coupling and deprotection reactions as well as washing steps take place simultaneously. The

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• : Experimental procedures and NMR spectra of compounds 6–9, 11–13, 15–19, 21–24, 26–28, 30, 31, 33, 34, 36–41 and S1. Acknowledgements O. R., M. B. and C. D. thank the Deutsche Forschungsgemeinschaft (DFG, SFB 803 "Functionality controlled by organization in and between membranes") and the Fonds der Chemischen

From porphyrin benzylphosphoramidate conjugates to the catalytic hydrogenation of 5,10,15,20-tetrakis(pentafluorophenyl)porphyrin

• Marcos C. de Souza,
• Leandro F. Pedrosa,
• Géssica S. Cazagrande,
• Vitor F. Ferreira,
• Maria G. P. M. S. Neves and
• José A. S. Cavaleiro

Beilstein J. Org. Chem. 2014, 10, 628–633, doi:10.3762/bjoc.10.54

• that the efficiency of the drug greatly depends on the porphyrin amphiphilicity, which must provide good interactions with the lipid membranes and the physiological medium. Consequently, tumor localization and better selectivity can be achieved by introducing polar substituents [3]. For this reason, we

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• -held specific cation (sodium in the case of monensin A) while the external surface is exclusively non-polar. This confers the ability to transport the cation across cell membranes leading to dissipation of the membrane potential and cell death. The toxicity of polyethers has limited their clinical use

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• bioavailability of 38 was poor, and this was attributed to the basicity of the secondary amine group which made the molecule positively charged at physiological pH and hence unable to traverse biological membranes. This problem was overcome by introducing a fluorine atom onto the piperidine ring (39): the