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

• anaesthesia. Keywords: active pharmaceutical ingredient; binding constant; cyclodextrin; derivatization; gas chromatography; sevoflurane; substitution pattern; Introduction Cyclodextrins (CDs) are cyclic oligomers of α-1,4-linked glucose units. Those CDs consisting of 6, 7, and 8 glucose units are called α

Synthesis of modified cyclic and acyclic dextrins and comparison of their complexation ability

• Kata Tuza,
• László Jicsinszky,
• Tamás Sohajda,
• István Puskás and
• Éva Fenyvesi

Beilstein J. Org. Chem. 2014, 10, 2836–2843, doi:10.3762/bjoc.10.301

• , HP-maltotetraoses in the corresponding HP-oligomers was not successful. The chromatogram in Figure S14 (Supporting Information File 1) shows HP-maltohexaose compared to maltohexaose and O-benzylmaltohexaose. We assumed that the 2-hydroxypropylated derivatives have the same purity as the intermediary

Mono- and multilayers of molecular spoked carbazole wheels on graphite

• Stefan-S. Jester,
• A. Vikas Aggarwal,
• Daniel Kalle and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 2783–2788, doi:10.3762/bjoc.10.295

• might form cocrystals with other polygons, thus patterns of increased complexity and larger lattice constants become feasible. Our MSW 2 and its precursor 1 were recently investigated by means of single-molecule photoluminescence spectroscopy as model compounds for conjugated oligomers commonly used in

Synthesis and properties of novel star-shaped oligofluorene conjugated systems with BODIPY cores

• Clara Orofino-Pena,
• Diego Cortizo-Lacalle,
• Joseph Cameron,
• Muhammad T. Sajjad,
• Pavlos P. Manousiadis,
• Neil J. Findlay,
• Alexander L. Kanibolotsky,
• Dimali Amarasinghe,
• Peter J. Skabara,
• Tell Tuttle,
• Graham A. Turnbull and
• Ifor D. W. Samuel

Beilstein J. Org. Chem. 2014, 10, 2704–2714, doi:10.3762/bjoc.10.285

• . All the oligomers of the Y-Bn (n = 1−4) series feature a reduction wave corresponding to the formation of a radical anion in the BODIPY core [36], but its position and reversibility varies for the different members of the family, being reversible and at a less negative potential for Y-B1 (E1/2 = −1.14

• one is irreversible for all the compounds. The second reduction wave corresponds to the formation of a dianion, most likely localised on the BODIPY core and partially delocalised on the arms. In contrast to the Y-Bn (n = 1–4) series, the reduction of oligomers from the T-Bn (n = 1–4) family exhibits

• levels for both families are similar, whereas, in general, the LUMO levels of the Y-Bn family are lower, leading to narrower electrochemical HOMO–LUMO gaps. Optical properties The optical properties of the oligomers were studied in dichloromethane solutions. An image of toluene solutions of both families

Galactan synthesis in a single step via oligomerization of monosaccharides

• Marius Dräger and
• Amit Basu

Beilstein J. Org. Chem. 2014, 10, 2658–2663, doi:10.3762/bjoc.10.279

• observations suggest that desilylation is most likely the result of transient Brønsted acid formation during the reaction and not due to fluoride ion generation. In an attempt to tune silyl ether deprotection rates and promote formation of longer oligomers, we examined the glycosylation of a bulkier TBDPS

• the donor to a solution of 3 and La(ClO4)3 might reduce self-oligomerization. However, addition of 2 via a syringe pump did not significantly improve the yields, nor did it shift the product distribution to longer oligomers. The use of La(ClO4)3 as the promoter appears to be critical in this reaction

• shifted the product distribution towards longer oligomers (Table 1, entry 9). Somewhat surprisingly, the addition of another 0.5 equivalent of 2 after 120 minutes of reaction did not appear to significantly perturb either the overall yields or product distributions (Table 1, entry 10). We found that

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

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer) to CRM197. Moreover, improvements in

• the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide. Keywords: carbohydrates; glycoconjugates; immunology; multivalent glycosystems Neisseria meningitidis

• ]. This could be a crucial feature to improve batch-to-batch consistency in vaccine manufacturing and to confer a better safety profile. Some of us have recently achieved the first synthesis of short-chain MenX CPS oligomers (compounds 1–3, Figure 1) provided with a phosphodiester-linked aminopropyl

Oligomerization of optically active N-(4-hydroxyphenyl)mandelamide in the presence of β-cyclodextrin and the minor role of chirality

• Helmut Ritter,
• Antonia Stöhr and
• Philippe Favresse

Beilstein J. Org. Chem. 2014, 10, 2361–2366, doi:10.3762/bjoc.10.246

• from horseradish or iron(II)-salen were used as catalysts. The obtained yellow powdery oligomers 2 show high solubility in many commonly used organic solvents like acetone, THF, ethanol, methanol, acetonitrile and 1,4-dioxan. Because of the broad signals of the oligomers 2 in the 1H NMR spectra the

• measurements indicate the formation of oligomers 2 from the monomer 1 as shown in Figure 2. As expected the repetitive unit has a molecular mass of 241 g/mol, which confirms the linkage of the monomers via a formal abstraction of two hydrogen atoms. The highest molecular weight oligomers 2 obtained through

• enzymatic oligomerization consists of up to 10 repetitive units which could be detected by MALDI–TOF MS measurements. Furthermore comparable molecular weights are accessible through oligomerization of 1 with iron(II)-salen as catalyst. Here oligomers 2 with up to 8 repetitive units are detectable. The

Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid

• Keunsoo Kim,
• Venkateshwarlu Punna,
• Phaneendrasai Karri and
• Ramanarayanan Krishnamurthy

Beilstein J. Org. Chem. 2014, 10, 2131–2138, doi:10.3762/bjoc.10.220

• were achieved with N4-isobutyrylcytosine as the nucleophile [19][20][21]. In the guanine series, the N2-isobutyryl, O6-diphenylcarbamoyl protected guanine worked well (Scheme 3) [22]. With all the four phosphoramidites in hand we proceeded to the automated synthesis of the oligomers, which proceeded

• prepare the phosphoramidite 28, and proceeded with the oligomer synthesis for our studies. However, this was far from satisfactory, and the continued demand for isoGNA oligomers within our group and our collaborative work prompted us to look for an improvement of the preparation of the adenine building

Building complex carbon skeletons with ethynyl[2.2]paracyclophanes

• Ina Dix,
• Lidija Bondarenko,
• Peter G. Jones,
• Thomas Oeser and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 2013–2020, doi:10.3762/bjoc.10.209

• Sonogashira coupling) [7]. For the smaller oligomers (dimers, trimers) the ortho-isomer with its opening angle of 60° between the ethynyl functions leads preferentially to (mono)cyclic hydrocarbons. For the meta-compound 3 we can expect both cyclic and acyclic (linear) products, and when the two ethynyl

• moieties are anchored in para-position, 5, the lower oligomers can no longer be cyclic because they would be too highly strained. When two ethynyl groups are placed into the benzene rings of [2.2]paracyclophane, the situation changes. In a strict sense the analog of 1,2-diethynylbenzene (1) is 4,5

Synthesis of 2-substituted tryptophans via a C3- to C2-alkyl migration

• Michele Mari,
• Simone Lucarini,
• Francesca Bartoccini,
• Giovanni Piersanti and
• Gilberto Spadoni

Beilstein J. Org. Chem. 2014, 10, 1991–1998, doi:10.3762/bjoc.10.207

• et al. [45][46][47][48][49][50] showing an intramolecular rearrangement to yield 2,3-disubstituted indoles using TFA or diluted HCl, our synthetic procedure did not work with the addition of these acids, and only some indole oligomers were obtained. The best yield and reactivity were obtained by

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• are among the best methods to prepare C-arylglycosides, C-nucleosides and C-glycosidic oligomers when new artificial pharmacophores are approached [17]. With Suzuki cross-couplings C-glycoside analogues of phloriain with antidiabetic properties [18] or aryl-scaffolded dimers and trimers were

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• the EDS based di- and trivalent glycooligomers giving the highest binding affinity with IC50 values of 2.0 and 3.2 µM, respectively. The corresponding di- and trivalent oligomers containing the AZO spacer instead of the EDS unit show higher IC50 values for both E- and Z-isomers, i.e., a slightly less

Influence of perylenediimide–pyrene supramolecular interactions on the stability of DNA-based hybrids: Importance of electrostatic complementarity

• Christian B. Winiger,
• Simon M. Langenegger,
• Oleg Khorev and
• Robert Häner

Beilstein J. Org. Chem. 2014, 10, 1589–1595, doi:10.3762/bjoc.10.164

• aedamers (aromatic electron donor acceptor oligomers) pioneered by Iverson and coworkers [18][36][37]. They consist of face-to-face stacked electron-rich naphthalene and electron-poor naphthalenediimide (NDI) chromophores and belong to the broader area of foldamers [38]. DNA has been described as a

• molecular scaffold for arranging various types of chromophores [39][40][41][42][43][44]. Recently, we reported that oligoarenotides (oligomers with an alternating phosphodiester-aromatic hydrocarbon motif) exhibit similar structural properties as nucleic acids, and although the aromatic hydrocarbons cannot

• strands proceeds in a selective manner, the chromophores on opposite strands interdigitate and stack face-to-face in an organised controlled assembly. Results and Discussion The principle of the system is illustrated in Figure 1. All oligomers are composed of a DNA part and a modified section containing a

Pyrene-modified PNAs: Stacking interactions and selective excimer emission in PNA₂DNA triplexes

• Alex Manicardi,
• Lucia Guidi,
• Alice Ghidini and
• Roberto Corradini

Beilstein J. Org. Chem. 2014, 10, 1495–1503, doi:10.3762/bjoc.10.154

• click chemistry or as a masked amino group both in a PNA monomer and in PNA oligomers, allowing to produce a variety of modified PNAs from a single precursor [35]. This chemistry introduces a moderate degree of flexibility which can be useful for allowing interactions with other groups to occur within

• -azidomethyluracil precursor, as described previously [35], whereas a pyrene-containing modified monomer 1 (Scheme 1), more suitable for automated synthesis, was designed for the realization of all the other oligomers (PNA2–6, Figure 1c). For the synthesis of the modified monomer bearing the pyrene moiety, we

• ), then linear gradient to 50% MeCN 0.2% FA in 30 minutes at a flow rate of 1 mL/min). PNA oligomers were purified with RP-HPLC using a XTerra Prep RP18 column (7.8 × 300 mm, 10 μm) (method B, linear gradient from H2O 0.1% TFA to 50% MeCN 0.1% TFA in 30 minutes at a flow rate of 4.0 mL/min). HRMS were

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores

• Mathieu L. Lepage,
• Alessandra Meli,
• Anne Bodlenner,
• Céline Tarnus,
• Francesco De Riccardis,
• Irene Izzo and
• Philippe Compain

Beilstein J. Org. Chem. 2014, 10, 1406–1412, doi:10.3762/bjoc.10.144

• scaffold is crucial as it defines the valency, the size and the shape of the multivalent architectures. Due to their broad chemical diversity, rapid and convenient synthetic access, improved proteolytic stability and cell permeability over peptides, N-substituted glycine oligomers, called peptoids [14][15

• scaffolds (2–4, Figure 1) were prepared using the sub-monomer approach developed by Zuckerman et al. [44] through a two-step sequence, repeated iteratively, to obtain the desired oligomers (Scheme 1). Each monomer is constructed on the 2-chlorotrityl resin from C- to N-terminus using N,N

• ’-diisopropylcarbodiimide (DIC)-mediated acylation with bromoacetic acid, followed by amination with the propargyl amine. After the completion of synthesis, the oligomers were cleaved from the resin using a 4:1 solution of CH2Cl2/hexafluoroisopropanol (HFIP). Macrocyclizations of the linear N-substituted oligoglycines 6–8

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

• processes and offer an enormous potential to encrypt biological information [1][2][3][4]. In contrast to the linear nucleic acids and proteins, carbohydrates usually form branched oligomers or polymers which are joined together by a variety of linkages. The vast amount of resulting carbohydrate oligomers

Homochiral BINOL-based macrocycles with π-electron-rich, electron-withdrawing or extended spacing units as receptors for C₆₀

• Marco Caricato,
• Silvia Díez González,
• Idoia Arandia Ariño and
• Dario Pasini

Beilstein J. Org. Chem. 2014, 10, 1308–1316, doi:10.3762/bjoc.10.132

• remove by flash column chromatography. These byproducts were tentatively characterized as higher oligomers from their NMR pattern. The UV–vis absorption spectra in EtOH of a selection of macrocyclic compounds (3b, 3d, 4b and 4d with π-electron rich and π-electron deficient spacing units, Figure S1

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

• generally no tertiary, three-dimensional structure compared to proteins [1]. In nature, the oligomers or polymers are assembled at ribosomes by aminoacyl-tRNAs (transfer ribonucleic acid) [2]. Basically, a condensation reaction of a carboxylic acid moiety with a functional amine of trifunctional α-amino

• . Moreover, the reaction cycles are very short compared to solution synthesis, which allows faster manufacturing [20]. Additionally, the solid-phase concept is not only an elegant way to build up peptides but also other oligomers such as polyamides [26], polynucleotides [27] and polysaccharides [28]. This

Solid-phase-supported synthesis of morpholinoglycine oligonucleotide mimics

• Tatyana V. Abramova,
• Sergey S. Belov,
• Yulia V. Tarasenko and
• Vladimir N. Silnikov

Beilstein J. Org. Chem. 2014, 10, 1151–1158, doi:10.3762/bjoc.10.115

• . Keywords: labile linker; morpholino oligomers; oligonucleotide mimics; solid-phase-supported peptide synthesis (SPPS); Introduction The phosphorodiamidate morpholino oligomers (PMO) and peptide conjugated PMO (PPMO) are currently promising candidates for antisense therapy of a number of infectious and

• hereditary diseases [1][2][3][4] despite of some difficulties and limitations. They also proved to be valuable tools to study fundamental problems of gene expression in the course of embryogenesis [5][6]. A few examples of morpholino oligomers containing other types of internucleoside bonds were described

• . An attractive feature of these new morpholino oligonucleotide analogues is the absence of additional chiral centers. Unlike commercially available PMO and PPMO, which are mixtures of diastereomers, oligomers constructed with the use of phosphoromonoamidate [7], oxalyl diamide [8], amidine [9] and

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• polymerase to synthesize long single-stranded DNA that folds into an octahedron by assistance of scaffolding DNA oligomers [17]. In another approach rolling circle amplification was used for enzymatic amplification of DNA nanostructures [32][33]. Recently, this approach was extended to operate in cells [34

• respective DNA oligomers. Since we later intended to investigate whether the oligonucleotide branches are used as primers in PCR (vide infra), the oligonucleotides have to terminate with a free 3'-hydroxy group. This requires a particular synthesis strategy (Scheme 2). The synthesis strategy was adapted in a

• the synthesis of both DNA strands. Following this approach a series of branched oligonucleotides were synthesized (Figure 1). The average coupling yield was always higher than 95% requiring a coupling time of 5 min only for the reaction of 6. DNA-oligomers were purified twice by HPLC and characterized

Consecutive isocyanide-based multicomponent reactions: synthesis of cyclic pentadepsipeptoids

• Angélica de Fátima S. Barreto,
• Otilie E. Vercillo,
• Ludger A. Wessjohann and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2014, 10, 1017–1022, doi:10.3762/bjoc.10.101

• ]. This family of oligomers comprising poly-N-substituted glycines mimics the primary natural structure of peptides and exhibits greater proteolytic stability and increased cellular permeabilities in comparison to peptides [5][6][7]. A powerful synthetic tool for the preparation of a peptoid backbone is

Molecular architecture with carbohydrate functionalized β-peptides adopting 3₁₄-helical conformation

• Nitin J. Pawar,
• Navdeep S. Sidhu,
• George M. Sheldrick,
• Dilip D. Dhavale and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2014, 10, 948–955, doi:10.3762/bjoc.10.93

• oligomers varying the sugar (glucose, galactose, xylose) and sugar protecting groups. The influence of sugar units and the configuration of sugar-β-amino acids on β-peptide secondary structure were investigated by CD spectroscopy. Keywords: carbohydrate recognition; conformation; glycopeptide; β-peptide

• groups still being protected (Figure 2). Further, oligomers 1 and 7 were debenzylated using H2, 10% Pd/C to β-glycopeptides 2 and 8, respectively. The acetonide groups in the galactosyl and xylosyl sugar units were deprotected simultaneously along with the Boc-groups and cleavage from solid support using

• % depending on the kind of sugar units incorporated. Oligomers 1–6 all have in common the (S)-configuration for the β3-sugar side chains; this is in agreement with the right-handed 314-helix and a positive Cotton effect. Nevertheless, β3-peptide 1 seems to provide a different structure and helical sense

The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

• Joscha Vollmeyer,
• Ute Baumeister and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 910–920, doi:10.3762/bjoc.10.89

• yield of 57%. The comparison of the GPC traces of the crude products of 1a and 1d shows that in the intramolecular reaction less oligomers are formed than in the intermolecular reaction. However, the yields of the cyclization reactions do not differ significantly. That indicates that in the template

• -mediated cyclization side reactions cannot be completely suppressed. In the statistical half ring dimerization, the most important side reaction is the oligomerization of the half rings. Beside the desired dimers also trimers, tetramers, and other oligomers are formed, which can undergo further

• oligomerization reactions or may cyclize. These cyclic oligomers are still soluble and therefore they can be detected by GPC. In case of the template connected half rings, we assume that the oligomers formed through an intermolecular reaction cross-link, most likely form insoluble polymers, and are therefore not

Metal and metal-free photocatalysts: mechanistic approach and application as photoinitiators of photopolymerization

• Jacques Lalevée,
• Sofia Telitel,
• Pu Xiao,
• Marc Lepeltier,
• Frédéric Dumur,
• Fabrice Morlet-Savary,
• Didier Gigmes and
• Jean-Pierre Fouassier

Beilstein J. Org. Chem. 2014, 10, 863–876, doi:10.3762/bjoc.10.83

• ][52][53][54][55]) in formulations containing multifunctional synthetic epoxides, acrylates, monomers/oligomers or epoxide/acrylate blends (renewable raw or modified materials are usable to some extent) with lights extending from the UV to the red, using polychromatic or monochromatic light sources