A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• substances such as pharmaceuticals or fragrances is exploited since it is cheap, harmless and biodegradable [4]. It is also a useful building block for sensors and/or capture devices, advanced materials, and even artificial enzymes. Most such uses require that compound 1 can be chemically modified so that

The role of chemistry in the success of oligonucleotides as therapeutics

• Pawan Kumar and
• Tom Brown

Beilstein J. Org. Chem. 2022, 18, 197–199, doi:10.3762/bjoc.18.22

• Pawan Kumar Tom Brown Takeda Development Center Americas, Inc. (TDCA), 9625 Town Centre Drive, San Diego, CA 92121, USA Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK 10.3762/bjoc.18.22 Keywords: antisense oligonucleotides; chemically modified

• forefront of solving these issues, and have introduced many chemically modified nucleotides into oligonucleotides to increase their binding affinity toward RNA targets, and to improve their stability against nucleases to slow down degradation. This strategy has been successful, and most oligonucleotide

• -based drugs that have been approved by the FDA contain chemically modified nucleotides (Figure 1) indicating the critical role chemists have played in bring oligonucleotides from bench to bedside. Importantly, a plethora of different chemically modified nucleotides have been described in the literature

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• electrostatic repulsion. In the following sections, a series of ASO-type oligonucleotides (ONs) which have been chemically modified with positively charged groups will be described, and their properties highlighted. Review ONs containing amine-group conjugates and nucleotide derivatives Many parameters can

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• the triplexes was still lower than that of the Watson–Crick PNA–DNA and PNA–RNA duplexes and required a tract of at least 15 consecutive purines for chemically-modified triplex-forming PNA to achieve low nanomolar binding [26]. Triple-helical binding of PNA to dsRNA was not explored until 2010 when

Antiviral therapy in shrimp through plant virus VLP containing VP28 dsRNA against WSSV

• Santiago Ramos-Carreño,
• Ivone Giffard-Mena,
• Jose N. Zamudio-Ocadiz,
• Alfredo Nuñez-Rivera,
• Ricardo Valencia-Yañez,
• Jaime Ruiz-Garcia,
• Maria Teresa Viana and
• Ruben D. Cadena-Nava

Beilstein J. Org. Chem. 2021, 17, 1360–1373, doi:10.3762/bjoc.17.95

• , damaging the VLPs. Therefore, further studies should be on how this can be administered in the pellets at industrial levels. Other studies by IM injection of chemically modified chitosan nanoparticles loaded with anti-VP28 RNA [20] and antisense plasmid constructs for VP28 [24] have shown protection of 95

• CCMV (data not shown). Furthermore, these VLPs can be chemically modified with a peptide or using protein engineering, to express on its external surface to better recognize (target) the WSSV infected cells increasing the antiviral therapy efficiency. Because new viral outbreaks are the primary threat

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• techniques, such as crystallography, have provided insights to rationalize numerous properties including binding affinity, nuclease stability, and trends observed in the gene silencing. In this review, we discuss the chemistry, biophysical, and structural properties of a number of chemically modified

• oligonucleotides that have been explored for gene silencing. Keywords: antisense; chemically modified oligonucleotides; crystallography; siRNA; structure; Introduction The natural nucleic acids sugar-phosphate backbone comes in two flavors, 2'-deoxyribose in DNA and ribose in RNA. However, this relative

DNA with zwitterionic and negatively charged phosphate modifications: Formation of DNA triplexes, duplexes and cell uptake studies

• Yongdong Su,
• Maitsetseg Bayarjargal,
• Tracy K. Hale and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2021, 17, 749–761, doi:10.3762/bjoc.17.65

• The ability to detect and modify the genome of living organisms is important for the diagnosis, prevention, and treatment of many diseases [1]. The site-specific targeting and manipulation of genomic DNA or RNA using chemically modified short oligodeoxynucleotides (ONs) is considered to be a viable

• ]. The major challenge in designing chemically modified ONs as antigene/antisense agents is to ensure an efficient cellular uptake and nuclease resistance while still maintaining, or ideally increasing, binding affinity and specificity of the ONs towards their DNA or RNA target. Many synthetic analogues

• various positions in the sequence. The thermal stability of a parallel DNA triplex and duplexes of DNA and RNA formed with these ONs where then evaluated. Thermal denaturation experiments, nuclease resistance and cell-uptake assays were also conducted to evaluate these chemically modified ONs. Results

Synthesis, structural characterization, and optical properties of benzo[f]naphtho[2,3-b]phosphoindoles

• Mio Matsumura,
• Takahiro Teramoto,
• Masato Kawakubo,
• Masatoshi Kawahata,
• Yuki Murata,
• Kentaro Yamaguchi,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2021, 17, 671–677, doi:10.3762/bjoc.17.56

• phosphorus center can be easily chemically modified and converted to phosphole derivatives with different electronic properties by reactions such as oxidation, alkylation, and coordination to a Lewis acid [1][2][3][4][5][6][7][8]. Theoretically, pentacyclic benzonaphthophosphindole contains six structural

• , molecular structure, and optical properties of 6-phenyl-6H-benzo[f]naphtho[2,3-b]phosphoindole (F) and the derivatives in which the phosphorus atom is chemically modified, such as a phospholium salt and the borane–phosphine complex. Results and Discussion Treatment of 3,3′-dibromo-2,2′-binaphthyl (1) [21

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• of known, in vivo effective substances but also for designing chemically modified analogs as valid alternatives for further therapeutic agents. Keywords: bioactive compounds; enyne metathesis; ring-closing metathesis; ruthenium catalysts; tandem reactions; Introduction Alkene and alkyne metathesis

A review of asymmetric synthetic organic electrochemistry and electrocatalysis: concepts, applications, recent developments and future directions

• Munmun Ghosh,
• Valmik S. Shinde and
• Magnus Rueping

Beilstein J. Org. Chem. 2019, 15, 2710–2746, doi:10.3762/bjoc.15.264

• summarized the background and recent advances and arranged this article to provide a systematic description of electrochemical reactions in which chirality has been induced using these three sources (Figure 1). Chemically modified chiral electrodes Electrochemical asymmetric reductions using chiral

• cathodes in the presence of chiral inductors, including tertiary amines, optically active proteins, and alkaloids [19][20], in 1975, Miller’s group reported the first example of the modification of electrodes via covalent binding [21]. They chemically modified air-oxidized graphite electrodes via treatment

• acid produced (R)-(−)-2-hexanol with almost the same optical purity. Similar results were observed when 2-heptanone and 2-octanone were used as substrates (Scheme 2). The above results confirm that chemically modified chiral electrodes are a useful platform for asymmetric induction because they require

Synthesis of polydicyclopentadiene using the Cp₂TiCl₂/Et₂AlCl catalytic system and thin-layer oxidation of the polymer in air

• Zhargolma B. Bazarova,
• Ludmila S. Soroka,
• Alex A. Lyapkov,
• Мekhman S. Yusubov and
• Francis Verpoort

Beilstein J. Org. Chem. 2019, 15, 733–745, doi:10.3762/bjoc.15.69

• possibility of the formation of a thin film of a chemically modified polymer, which reduces its permeability to corrosive media. We assume that in case of PDCPD oxidation, the formation of chemically modified polymer layers also occurs, which reduce the permeability of the film to oxygen. The double bonds

Chemical structure of cichorinotoxin, a cyclic lipodepsipeptide that is produced by Pseudomonas cichorii and causes varnish spots on lettuce

• Hidekazu Komatsu,
• Takashi Shirakawa,
• Takeo Uchiyama and
• Tsutomu Hoshino

Beilstein J. Org. Chem. 2019, 15, 299–309, doi:10.3762/bjoc.15.27

• 13C NMR signals of cichorinotoxin, and we determined the stereochemistry of 12 out of the 22 amino acids. In addition, we prepared chemically modified derivatives of cichorinotoxin and evaluated the abilities of some derivatives to cause lettuce rot, in order to provide insight into which structural

Fabrication of supramolecular cyclodextrin–fullerene nonwovens by electrospinning

• Hiroaki Yoshida,
• Ken Kikuta and
• Toshiyuki Kida

Beilstein J. Org. Chem. 2019, 15, 89–95, doi:10.3762/bjoc.15.10

• promising as an approach for fiber functionalization, the scope is limited to cases with 1:1 inclusion complexes and chemically modified CD. Fullerenes have been widely studied in the fields of chemistry and materials science because they have attractive chemical structures and good electron acceptor

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

• as a result of binding to minor groove DNA. Samanta et al. investigated a thorough structure–activity correlation between mahanine, an anticancer carbazole alkaloid, and its chemically modified analogs to test the role of various functional groups on its antiproliferative activity against 19 cancer

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• the release of the active drug will not be perturbed. In case that the drug binds through recognition of a specific receptor, in silico approaches have to be recruited in order to rationally select the location of the drug that will be chemically modified [18]. Furthermore, it must be sufficiently

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• group; oligonucleotide prodrugs; reduction-responsive; stimuli-responsive nucleic acids; thermolytic prodrugs; Introduction For past decades, oligonucleotide-based therapies have been widely developed using short synthetic oligonucleotides (ONs) and their chemically modified mimics as powerful tools to

• active biomolecules. Here, we summarize the chemically modified ONs that are responsive to either internal biochemical regulatory stimuli such as glutathione or enzymes (reductases, carboxyesterases), or external physical stimuli such as heat or light (photoirradiation). The transient responsive units

Position-dependent impact of hexafluoroleucine and trifluoroisoleucine on protease digestion

• Susanne Huhmann,
• Anne-Katrin Stegemann,
• Kristin Folmert,
• Damian Klemczak,
• Johann Moschner,
• Michelle Kube and
• Beate Koksch

Beilstein J. Org. Chem. 2017, 13, 2869–2882, doi:10.3762/bjoc.13.279

• , backbone-extended or chemically modified amino acids [1]. In this regard, the incorporation of fluorine into amino acids has become a promising strategy. Fluorine’s unique properties, namely low polarizability, a strong inductive effect, and high electronegativity, as well as its small size, result in

Synthesis and supramolecular properties of regioisomers of mononaphthylallyl derivatives of γ-cyclodextrin

• Markéta Bláhová,
• Sergey K. Filippov,
• Lubomír Kováčik,
• Jiří Horský,
• Simona Hybelbauerová,
• Zdenka Syrová,
• Tomáš Křížek and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2017, 13, 2509–2520, doi:10.3762/bjoc.13.248

• 6, 7 or 8 glucose units, respectively. Both chemically modified and native CDs are used in numerous applications, e.g., in separation methods [2][3] or in the pharmaceutical industry [4][5]. CDs are well-known as host molecules for various guest substances in aqueous solutions [4]. Derivatives of

Synthesis and application of trifluoroethoxy-substituted phthalocyanines and subphthalocyanines

• Satoru Mori and
• Norio Shibata

Beilstein J. Org. Chem. 2017, 13, 2273–2296, doi:10.3762/bjoc.13.224

• environmental burden [61][62]. An unsymmetrical type of TFEO-ZnPc with ethynyl group (4) shows high solubility in Solkane® 365 mfc while a Glaser-type coupling reaction catalyzed by copper with Solkane® 365 mfc as the medium have been reported (Scheme 2) [63]. In this way, TFEO-Pc can be chemically modified in

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• control group indicated that click chemistry was not affected by the compounds (Figure 5D). To assess the stability of the probe, we incubated CA2 with two of the most active compounds, 11 and 14. NMR and MS data indicate that the probe was not chemically modified even after 18 and 24 h so that the

Interactions between cyclodextrins and cellular components: Towards greener medical applications?

• Loïc Leclercq

Beilstein J. Org. Chem. 2016, 12, 2644–2662, doi:10.3762/bjoc.12.261

• based on the ability of CDs to extract lipids from the cell membrane. The objective of this contribution is to focus on the potential use of natural and chemically modified CDs in the vast array of medical and biological applications. Review Cyclodextrins: synthesis, structure and physicochemical

• stomatocyte or echinocyte) depending on the cavity size of the CDs. For instance, α- and γ-CD induce progressive shape changes from discocytes into stomatocytes and from stomatocytes into spherocytes [58]. In contrast, β-CD leads only to swelling of erythrocytes. Similar effects are found for chemically

• modified CDs. For instance, Motoyama et al. have reported morphological changes in erythrocytes induced by methylated CDs such as 2,6-di-O-methyl-α-CD and 2,6-di-O-methyl-β-CD (DM-α-CD and DM-β-CD) [72][73]. The authors reported that DM-α-CD induces morphological changes in rabbit erythrocytes leading to

DNA functionalization by dynamic chemistry

• Zeynep Kanlidere,
• Oleg Jochim,
• Marta Cal and
• Ulf Diederichsen

Beilstein J. Org. Chem. 2016, 12, 2136–2144, doi:10.3762/bjoc.12.203

• functional groups into its native structure [10][11]. Such chemically modified oligonucleotides are useful intermediates for their subsequent functionalization through post-synthetic protocols [11][12][13]. Within a post-synthetic strategy, a nucleotide analog is modified with a reactive functional group

Interactions between 4-thiothymidine and water-soluble cyclodextrins: Evidence for supramolecular structures in aqueous solutions

• Vito Rizzi,
• Sergio Matera,
• Paola Semeraro,
• Paola Fini and
• Pinalysa Cosma

Beilstein J. Org. Chem. 2016, 12, 549–563, doi:10.3762/bjoc.12.54

• outside of the CDs cavity results in the hydrophilic character of the molecules [6][7][14]. Different chemically modified CDs are known in literature, which are characterized by a higher water solubility compared with the native CDs. These CDs, i.e., 2-HP-CDs, are widely used [15]. An enhanced solubility

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies

• Giuseppina Raffaini,
• Fabio Ganazzoli and
• Antonino Mazzaglia

Beilstein J. Org. Chem. 2016, 12, 73–80, doi:10.3762/bjoc.12.8

• , Farmaceutiche ed Ambientali dell’Università di Messina, V. le F. Stagno d'Alcontres 31, 98166 Messina, Italy 10.3762/bjoc.12.8 Abstract Chemically modified cyclodextrins carrying both hydrophobic and hydrophilic substituents may form supramolecular aggregates or nanostructures of great interest. These systems