Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• were equipped with two benzyl ethers to account for the low reactivity of glucuronic acids as glycosylating agents and carried either Fmoc or Lev groups. As solid support, we chose photolabile-linker-functionalized Merrifield resin 4 for its compatibility with the activation conditions for glycosyl

• ]. The building blocks were synthesized in high yields using standard protecting group chemistry (see Supporting Information File 1). Solid support 4 was prepared according to an established procedure [28]. The automated glycosylation protocol employed three times three equivalents of building block to

• maintained for 30 min. The temporary Fmoc protecting group was cleaved with triethylamine in DMF (N,N-dimethylformamide; 10% v/v). The Lev protecting group was removed using hydrazine monohydrate in pyridine/acetic acid (3:2 v/v). The crude oligosaccharide products were cleaved from the solid support by

Enantioselective carbenoid insertion into C(sp³)–H bonds

• J. V. Santiago and
• A. H. L. Machado

Beilstein J. Org. Chem. 2016, 12, 882–902, doi:10.3762/bjoc.12.87

• to perform an enantioselective insertion of the carbenoid into benzylic C(sp3)–H bonds and similar results were observed [49]. In 2011, the same research group developed a new heterogeneous copper catalyst for carbenoid insertion into C(sp3)–H bonds [50]. The solid support was based on SiO2/Al2O3 and

Three new trixane glycosides obtained from the leaves of Jungia sellowii Less. using centrifugal partition chromatography

• Luíse Azevedo,
• Larissa Faqueti,
• Marina Kritsanida,
• Antonia Efstathiou,
• Despina Smirlis,
• Gilberto C. Franchi Jr,
• Grégory Genta-Jouve,
• Sylvie Michel,
• Louis P. Sandjo,
• Raphaël Grougnet and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2016, 12, 674–683, doi:10.3762/bjoc.12.68

• complexity, and frequently have more advantageous ADME/T properties [18]. Compared to other chromatographic methods, centrifugal partition chromatography (CPC) is compatible with green chemistry criteria since it does not use any polluting solid support such as silica. Moreover, it allows the complete

Effective immobilisation of a metathesis catalyst bearing an ammonium-tagged NHC ligand on various solid supports

• Krzysztof Skowerski,
• Jacek Białecki,
• Stefan J. Czarnocki,
• Karolina Żukowska and
• Karol Grela

Beilstein J. Org. Chem. 2016, 12, 5–15, doi:10.3762/bjoc.12.2

• was ascribed to the low surface area of this material. Therefore, we decided to deposit 8 on a solid support characterised by a high surface. The initially chosen support for the catalyst deposition was activated carbon (charcoal, C*), which is known to have a high surface area [51]. Addition of C* to

• on activated carbon (8-C*) we were eager to test its catalytic properties. A model ring-closing metathesis (RCM) reaction leading to product 10 (Scheme 2) was used to check the influence of temperature and concentration on the activity of 8 on the solid support. We observed that the use of higher

Reactions of nitroxides 15. Cinnamates bearing a nitroxyl moiety synthesized using a Mizoroki–Heck cross-coupling reaction

• Jerzy Zakrzewski and
• Bogumiła Huras

Beilstein J. Org. Chem. 2015, 11, 1155–1162, doi:10.3762/bjoc.11.130

• a heterogeneous catalyst which is immobilized on a solid support. In addition to the widely highlighted unquestionable advantages of immobilized, heterogeneous catalysts (easy separation from the reaction mixture and the possibility of re-use), such catalysts are rigidly anchored on a carrier and

Multivalent polyglycerol supported imidazolidin-4-one organocatalysts for enantioselective Friedel–Crafts alkylations

• Tommaso Pecchioli,
• Manoj Kumar Muthyala,
• Rainer Haag and
• Mathias Christmann

Beilstein J. Org. Chem. 2015, 11, 730–738, doi:10.3762/bjoc.11.83

• of solid support such as polystyrene may lead to the disadvantage of operating in heterogeneous media. In contrast to the stepwise syntheses of dendrimers and dendron hybrids, the hyperbranched polymers can be easily obtained in kilogram scale through one-pot reactions [10], maintaining properties

Sequence-specific RNA cleavage by PNA conjugates of the metal-free artificial ribonuclease tris(2-aminobenzimidazole)

• Friederike Danneberg,
• Alice Ghidini,
• Plamena Dogandzhiyski,
• Elisabeth Kalden,
• Roger Strömberg and
• Michael W. Göbel

Beilstein J. Org. Chem. 2015, 11, 493–498, doi:10.3762/bjoc.11.55

• carboxylic acid 8, which after removal of the solvent was used for conjugation to PNA without further purification (Scheme 3). Conjugation of tris(2-aminobenzimidazole) 8 was performed with fully protected PNA-oligomers still bound to the solid support. To increase the solubility of the final product, 10mers

Highly selective generation of vanillin by anodic degradation of lignin: a combined approach of electrochemistry and product isolation by adsorption

• Dominik Schmitt,
• Carolin Regenbrecht,
• Marius Hartmer,
• Florian Stecker and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 473–480, doi:10.3762/bjoc.11.53

• amounts of acid will be required to rinse the product from the solid support, which is of significant advantage to the conventional approaches. The resulting lignin-containing waste streams could be incinerated for energy production and base recovery performed, as currently done with waste streams of the

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

• drug formulation such as “smart” plasters or bandages capable of prolonged release of the antiseptic drug. There are several examples of deposition of CD derivatives onto a solid support in the literature. The most common immobilization method is binding of various alkylthio-CDs onto a gold surface [16

• strongly influences the properties of the SAMs [16]. Similar assemblies/films can be prepared on glass surface, by depositing different CD-siloxanes [22][23]. Recently, some examples of anchoring CDs onto the solid support via ionic interactions were reported. Most of them describe deposition of cationic

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

NAA-modified DNA oligonucleotides with zwitterionic backbones: stereoselective synthesis of A–T phosphoramidite building blocks

• Boris Schmidtgall,
• Claudia Höbartner and
• Christian Ducho

Beilstein J. Org. Chem. 2015, 11, 50–60, doi:10.3762/bjoc.11.8

• synthesizer and base-mediated cleavage from the solid support, the desired full-length products were purified, isolated and identified by ESI mass spectrometry. The sequence of 30 and 31 resembled the sequence of model oligonucleotides 32 and 33 prepared for our initial studies on the NAA-modification [38

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• ) induced a “temporarily soluble” droplet of the nucleophile that can then intercept the N-acyliminium ion. Electrosynthesis have been adapted to use solid-supported bases [47][48][49][50][51], performing the electrosynthesis on compounds directly attached to a catch and release solid-support [52], or

Anomalous diffusion of Ibuprofen in cyclodextrin nanosponge hydrogels: an HRMAS NMR study

• Monica Ferro,
• Franca Castiglione,
• Carlo Punta,
• Lucio Melone,
• Walter Panzeri,
• Barbara Rossi,
• Francesco Trotta and
• Andrea Mele

Beilstein J. Org. Chem. 2014, 10, 2715–2723, doi:10.3762/bjoc.10.286

• obtained from samples not suitable for routine liquid state NMR. Cutting-edge examples taken from the recent literature include metabolomics [24][25], structure of organic ligands bound to a solid support [26], and catalysis [27]. In addition to providing structural information, HRMAS NMR has also been

Versatile synthesis of amino acid functionalized nucleosides via a domino carboxamidation reaction

• Vicky Gheerardijn,
• Jos Van den Begin and
• Annemieke Madder

Beilstein J. Org. Chem. 2014, 10, 2566–2572, doi:10.3762/bjoc.10.268

• carboxamidation procedure for the synthesis of modified nucleosides featuring two extra functional groups. Because hydrolysis of the methyl ester and removal of the t-Boc is performed during the standard cleavage of solid support using NH4OH and benzyl and benzoyl protecting groups can be removed by hydrogenation

Synthesis and optical properties of pyrrolidinyl peptide nucleic acid carrying a clicked Nile red label

• Nattawut Yotapan,
• Chayan Charoenpakdee,
• Pawinee Wathanathavorn,
• Boonsong Ditmangklo,
• Hans-Achim Wagenknecht and
• Tirayut Vilaivan

Beilstein J. Org. Chem. 2014, 10, 2166–2174, doi:10.3762/bjoc.10.224

• 2’-propargylated nucleotides and azide-modified Nile red [19]. An approach related to the latter was used in this work, although the azide function was placed on the PNA instead of the Nile red, and the clicking was carried out on the solid support rather than in solution phase. The propargylated

• completion of the synthesis, the N-terminal Fmoc group was removed and the free amino group was capped by acetylation. The acpcPNA on the solid support was spilt to 0.5 µmol portions for a further labeling experiment and treated with 1:1 dioxane/aqueous NH3 at 60 °C overnight to remove the nucleobase- and

• temperature overnight. After the reaction was completed, the labeled acpcPNA was cleaved from the solid support with trifluoroacetic acid (500 µL × 30 min × 3). After drying and washing with diethyl ether, the residue was purified by reversed-phase HPLC and characterized by MALDI–TOF mass spectrometry

Structure/affinity studies in the bicyclo-DNA series: Synthesis and properties of oligonucleotides containing bc^en-T and iso-tricyclo-T nucleosides

• Branislav Dugovic,
• Michael Wagner and
• Christian J. Leumann

Beilstein J. Org. Chem. 2014, 10, 1840–1847, doi:10.3762/bjoc.10.194

• building block revealed typically a drop of synthesis yield by roughly 20%. This was also reflected in the HPLC traces after final cleavage from the solid support (33% aq NH3, 55 °C, 16 h) which revealed besides the expected oligonucleotides ON1–3 also truncated sequences corresponding to 5’-phosphorylated

Convergent synthetic methodology for the construction of self-adjuvanting lipopeptide vaccines using a novel carbohydrate scaffold

• Vincent Fagan,
• Istvan Toth and
• Pavla Simerska

Beilstein J. Org. Chem. 2014, 10, 1741–1748, doi:10.3762/bjoc.10.181

• carbohydrate building block was coupled to the self-adjuvanting lipidic moiety (three lipidated Fmoc-lysines) on solid support. Four copies of a group A streptococcal B cell epitope (J8) were then conjugated to the glyco-lipopeptide using a copper-catalyzed cycloaddition reaction. The approach was elaborated

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

• block AZO. TDS allows for the conjugation of sugar azide ligands via the copper-catalyzed azide–alkyne cycloaddition (CuAAC). The synthesis and coupling on solid support of TDS and EDS has been previously described [7][10]. AZO was synthesized via Mills coupling adapting literature protocols [20][21][22

• steps, the oligomeric backbone was formed on the solid support. In the next step, the sugar ligands were introduced to the oligomeric backbone via CuAAC. To this end, two sugar azides (2-azidoethyl galactoside and 2-azidoethyl mannoside) were previously synthesized following literature protocols [26]. 8

• solid support followed by on-resin functionalization of alkyne side chains with sugar azide ligands and final cleavage from the support. Characterization of the E → Z photoisomerization (λ = 360 nm) of Azo-Gal(1,3,5)-5 in buffer solution at 25 °C via UV–vis absorption spectroscopy measurements

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

• assembled under heterogeneous conditions from the C- to the N-terminus on a polymeric solid “resin” [20]. The method was named solid-phase peptide synthesis and accounts for a peptide construction between two phases, an insoluble solid support and liquid soluble reagents [21]. Here, the first amino acid is

• coupled for the time of the synthesis with its carboxylic acid terminus to a resin that consists of polymer particles and protects the C-terminus from side reactions. In order to overcome aggregate formation, a distinct short organic linker is interposed between the amino acid and the solid support, which

• strategy is based on graded acid lability of permanent (also including the linkage to the solid support) and transient protecting groups (Scheme 3B). Whilst the Boc group has been used exclusively during the first years of SPPS, the introduction of the Fmoc-group [31] opened the path for a novel, more

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

• labile linker between the solid support and the growing oligomer chain (Figure 3) during SPPS in combination with the tert-butyloxycarbonyl (Boc)- and acyl-protected morpholino nucleosides. After completion of the synthesis, the cleavage of the oligomer from the solid support and the deprotection of

• nucleobases can be performed simultaneously by treatment with aqueous ammonia as in the solid phase synthesis of native oligonucleotides (ODN) [21]. The oxalyl-mediated attachment of the growing chain to the solid support is usual in the synthesis of base sensitive ODN derivatives [22]. Figure 3 indicates the

• after 4 h of the coupling reaction between monomers 5a,d,e and the Boc-Gly-PAM polymer resin. It was found that the cleavage of the monomers from the solid support in the course of the ammonia treatment was completed within two days at room temperature (see Supporting Information File 1). The structure

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

• branching molecules. The synthesis strategy was designed to meet the requirements of standard DNA solid support synthesis. Stepwise Sonogashira reaction was employed using the higher reactivity of iodide in the presence of bromide within 1,3-dibromo-5-iodobenzene (1) employing the known compounds 2 [41] and

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

• resin. Simultaneous tert-butyloxycarbonyl (Boc)-deprotection and cleavage of the β-glycopeptides from solid support using 5% trifluoroacetic acid (TFA) in dry dichloromethane provided β-glycopeptides D-glucose(Bn) 1 and 7, D-galactose(acetonide) 3, and D-xylose(Bn, acetonide) 5 with all sugar hydroxy

• 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

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• performance [118][119]. For example, the group of Nakamura used [CuBr·SMe2]2 as catalyst in THF to synthesize triazole-linked DNA analogues either in solution or on solid support [120]. Of the variety of sulfur-containing compounds tested by the group of Fu, thioanisole turned out to be a good ligand for

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• strain, which constitutively express D-arabinose isomerase (EC 5.3.1.3) [82]. An overall yield of 35% on a gram-scale was reported using this mutant strain [82]. Moreover, Yadav et al. immobilized galactose oxidase (EC 1.1.3.9) and catalase (EC 1.11.1.6) on a solid support (crab-shell particles or Ocimum

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• branched) [18] and biocompatible with a decreased risk of inherent immunogenicity [19]. Recently, we showed that monodisperse, sequence-defined glycooligomers obtained by sequential addition of building blocks on solid support are valuable tools for tuning and understanding carbohydrate–lectin interactions

• building blocks’ free carboxy group, coupling to the solid support followed by deprotection of the amino group (Figure 3). This allows us to synthesize chemically defined oligomers with full control over the monomer sequence [15][16][18][26] using differently functionalized and spacer building blocks. Due

• with 25% piperidine in DMF on solid support (Figure 3). Final deprotection from the resin was performed with TFA/DCM mixtures, followed by acetyl deprotection in solution under Zemplén conditions [44]. Although the glycosylated building blocks 9–13 suffer from steric hindrance and have a relatively