Synthesis of a novel category of pseudo-peptides using an Ugi three-component reaction of levulinic acid as bifunctional substrate, amines, and amino acid-based isocyanides

• Maryam Khalesi,
• Azim Ziyaei Halimehjani and
• Jürgen Martens

Beilstein J. Org. Chem. 2019, 15, 852–857, doi:10.3762/bjoc.15.82

• utilized to circumvent some of the problems associated with several natural peptides such as stability against proteolysis, poor bioavailability, receptor selectivity, and short duration of action [11]. The Ugi reaction allows the introduction of several substituents in its adducts to prepare novel

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• ]. As artemisinin has poor solubility and bioavailability, several derivatives of this natural product like artesunate and artemether were developed and are currently used in combination with other drugs for the treatment of malaria [4]. However, the exact mechanism of action of this endoperoxide

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• adhesion in mice [18][19]. These compounds have been extensively optimized in many works published by both groups, culminating in the identification of mannophosphates as prodrugs to increase oral bioavailability [20] and mannose C-glycosides, such as compound 6 , demonstrating enhanced in vivo metabolic

• plasma and liver microsomes, absence of cytotoxicity, and excellent oral bioavailability in mice. 4. Direct toxin inhibition Numerous bacteria secrete toxins that are responsible for acute virulence. Various small molecule and antibody approaches target the inhibition of bacterial toxins in order to

Strong binding and fluorescence sensing of bisphosphonates by guanidinium-modified calix[5]arene

• Jie Gao,
• Zhe Zheng,
• Lin Shi,
• Si-Qi Wu,
• Hongwei Sun and
• Dong-Sheng Guo

Beilstein J. Org. Chem. 2018, 14, 1840–1845, doi:10.3762/bjoc.14.157

• quality of pharmaceutical formulations, as well as monitoring drug plasma concentrations, analyzing drug biodistribution in bone tissue, and detecting drug excretion in urine. For example, BPs are of poor bioavailability if orally administered (generally with absorption less than 1%) and about 50% of the

Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination

• Jiyun Sun,
• Xiaohua Zhen,
• Huaibin Ge,
• Guangtao Zhang,
• Xuechan An and
• Yunfei Du

Beilstein J. Org. Chem. 2018, 14, 1452–1458, doi:10.3762/bjoc.14.123

• sciences. The introduction of this functional group in drug molecules can enhance their chemical and metabolic stability, improve their lipophilicity and bioavailability, and increase protein-binding affinity [1][2][3][4][5][6]. In this regard, the CF3 group has been introduced into many pharmaceutical

Synthetic avenues towards a tetrasaccharide related to Streptococcus pneumonia of serotype 6A

• Aritra Chaudhury,
• Mana Mohan Mukherjee and
• Rina Ghosh

Beilstein J. Org. Chem. 2018, 14, 1095–1102, doi:10.3762/bjoc.14.95

• SPn 6A in multicomponent vaccines like Pneumovax® has been recognized [15]. The low hydrolytic stability of the phosphodiester linkages in the clinical isolates of the SPn 6A polysaccharides poses a major drawback as it leads to low bioavailability [16]. Hence, the requirements of pure SPn 6A

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

Mechanochemistry of nucleosides, nucleotides and related materials

• Olga Eguaogie,
• Joseph S. Vyle,
• Patrick F. Conlon,
• Manuela A. Gîlea and
• Yipei Liang

Beilstein J. Org. Chem. 2018, 14, 955–970, doi:10.3762/bjoc.14.81

• ) which were agitated using a membrane valve [80]. Within three minutes, almost complete disruption of Gram-positive bacteria was effected enabling downstream analysis by quantitative PCR. Associative processes Variable drug bioavailability associated with crystal and co-crystal polymorphism can be

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

• diminishing expressed nucleoside receptors responsible for the cell uptake of gemcitabine [6]. Additionally, chemotherapy with anticancer agents is often hampered by their poor aqueous solubility, low oral bioavailability and metabolic instability. These drawbacks are linked to the unfavorable ADME

• linker tethering the transporting vehicle to the cytotoxic warhead, d) the “programmable” navigating/targeting moiety (i.e., receptor-specific ligand) and e) the “stealth” carrier (i.e., PEG) transfusing enhanced bioavailability. These modules are encoded in Figure 2A with different colors: the

Heterogeneous Pd catalysts as emulsifiers in Pickering emulsions for integrated multistep synthesis in flow chemistry

• Katharina Hiebler,
• Georg J. Lichtenegger,
• Manuel C. Maier,
• Eun Sung Park,
• Renie Gonzales-Groom,
• Bernard P. Binks and
• Heidrun Gruber-Woelfler

Beilstein J. Org. Chem. 2018, 14, 648–658, doi:10.3762/bjoc.14.52

• with phenylboronic acids yielding the corresponding biphenyls as product [7]. The biphenyl unit is a common structural motif in various pharmaceutically active agents and plays a crucial role in the binding affinity and the oral bioavailability of diverse APIs [8], including antihypertensive [9] and

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

• conjugate with a disulfide linker is favorable to improve the suppression of 2’,3’-cyclic nucleotide 3’-phosphodiesterase mRNA in oligodendrocytes in vivo. This result may be attributable to increased bioavailability of siRNA in the cytoplasm. Similarly, regarding the intracellular delivery of naked peptide

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

• to low oral bioavailability and a short half-life attributable in part to proteases of the digestive system and blood plasma [1][2][3][4][5][6][7][8]. Efficient approaches to overcome these limitations have been developed including the incorporation of non-natural amino acids, such as D-amino acids

One-pot three-component route for the synthesis of S-trifluoromethyl dithiocarbamates using Togni’s reagent

• Azim Ziyaei Halimehjani,
• Martin Dračínský and
• Petr Beier

Beilstein J. Org. Chem. 2017, 13, 2502–2508, doi:10.3762/bjoc.13.247

• fields of pharmaceuticals, agrochemicals, and materials sciences. The key properties such as metabolic and chemical stability, polarity, bioavailability, viscosity and lipophilicity can be altered in molecules containing the CF3 group in comparison with the nonfluorinated analogues. Numerous methods have

Structural diversity in the host–guest complexes of the antifolate pemetrexed with native cyclodextrins: gas phase, solution and solid state studies

• Magdalena Ceborska,
• Magdalena Zimnicka,
• Aneta Aniela Kowalska,
• Kajetan Dąbrowa and
• Barbara Repeć

Beilstein J. Org. Chem. 2017, 13, 2252–2263, doi:10.3762/bjoc.13.222

• pharmacokinetic properties of the guest molecule, such as water solubility, bioavailability and stability [6][7]. In particular, many important drugs in cancer treatment are often toxic and/or sparingly soluble or even insoluble in water. Among other methods, reversible derivatization of these drugs into CD

Solid-state studies and antioxidant properties of the γ-cyclodextrin·fisetin inclusion compound

• Joana M. Pais,
• Maria João Barroca,
• Maria Paula M. Marques,
• Filipe A. Almeida Paz and
• Susana S. Braga

Beilstein J. Org. Chem. 2017, 13, 2138–2145, doi:10.3762/bjoc.13.212

• resulting in a low oral bioavailability. This limitation can be overcome by using micro or nano-encapsulation methods that allow preparing fisetin oral liquid formulations that are well absorbed. Previously reported encapsulation strategies include liposomes [18], nanoemulsions [19], nanocochleates (which

Preparation of imidazo[1,2-a]-N-heterocyclic derivatives with gem-difluorinated side chains

• Layal Hariss,
• Kamal Bou Hadir,
• Mirvat El-Masri,
• Thierry Roisnel,
• René Grée and
• Ali Hachem

Beilstein J. Org. Chem. 2017, 13, 2115–2121, doi:10.3762/bjoc.13.208

• bioavailability for many drugs and pharmacological tools. So, the preparation of fluorinated molecules is a very attractive research area for organic and medicinal chemists [17][18][19][20]. Our research program aims to synthesize new fluorinated molecules based on the easy access and the versatility of

Peptide synthesis: ball-milling, in solution, or on solid support, what is the best strategy?

• Ophélie Maurin,
• Pascal Verdié,
• Gilles Subra,
• Frédéric Lamaty,
• Jean Martinez and
• Thomas-Xavier Métro

Beilstein J. Org. Chem. 2017, 13, 2087–2093, doi:10.3762/bjoc.13.206

• to improve their in vivo bioavailability and stability. This progresses empowered the potential of therapeutic peptides, suggesting a production surge in the future. Besides this high potential, actual peptide production techniques suffer from major environmental issues [4][5][6]. Indeed, large

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

• the enhancement of solubility, bioavailability and stability of drugs [2][3][4][5]. Moreover, being oligomers of α-D-glucopyranose, CDs possess an intrinsic chirality, thus they form diastereomeric inclusion complexes with enantiomeric pairs and frequently they exhibit enantioselectivity in aqueous

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• encapsulation of construct 6 into the liposomes improved the drug distribution in cancer cells and was followed by cell death. This new liposomal trilobolide derivative not only retains the biological properties of pure trilobolide, but also enhances the bioavailability, and thus has potential for the use in

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• of antivirals due to their stability in biological fluids and their bioavailability. Some years ago, we described an approach leading to the C-ribosylated analogue 1 of ribavirin (Figure 2) with the key-steps of the synthesis being an indium-mediated alkynylation of a ribose derivative followed by

Novel β-cyclodextrin–eosin conjugates

• Gábor Benkovics,
• Damien Afonso,
• András Darcsi,
• Szabolcs Béni,
• Sabrina Conoci,
• Éva Fenyvesi,
• Lajos Szente,
• Milo Malanga and
• Salvatore Sortino

Beilstein J. Org. Chem. 2017, 13, 543–551, doi:10.3762/bjoc.13.52

• property can be utilized to protect the guest molecules from oxidation and degradation, to enhance their solubility and bioavailability, or to use the CD host as a drug carrier [1]. The potential application of these macrocyclic sugars in such pharmaceutical formulations required the understanding of the

Extrusion – back to the future: Using an established technique to reform automated chemical synthesis

• Deborah E. Crawford

Beilstein J. Org. Chem. 2017, 13, 65–75, doi:10.3762/bjoc.13.9

• research into their bioavailability being conducted, but also into manufacturing techniques that could be utilised for their production. Currently, research into non-solvent based synthetic methods is being pursued to eliminate the influence that the solvent has over the cocrystal formed. Cocrystal

Synthesis of multi-lactose-appended β-cyclodextrin and its cholesterol-lowering effects in Niemann–Pick type C disease-like HepG2 cells

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

Beilstein J. Org. Chem. 2017, 13, 10–18, doi:10.3762/bjoc.13.2

• , and bioavailability of drugs. CDs improve the above properties of drugs through complex formation, when formulated as injectable solutions, sprays, eye drops, powders, and tablets [7][8]. In recent years, the efficacy of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in the treatment of the NPC disease has

Computational methods in drug discovery

• Sumudu P. Leelananda and
• Steffen Lindert

Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

• consumer market. It acts as a “virtual shortcut” in the drug discovery pipeline. CADD tools identify lead drug molecules for testing, can predict effectiveness and possible side effects, and assist in improving bioavailability of possible drug molecules. For example, in a recent study of CADD it was found

Tunable microwave-assisted method for the solvent-free and catalyst-free peracetylation of natural products

• Manuela Oliverio,
• Paola Costanzo,
• Monica Nardi,
• Carla Calandruccio,
• Raffaele Salerno and
• Antonio Procopio

Beilstein J. Org. Chem. 2016, 12, 2222–2233, doi:10.3762/bjoc.12.214

• Catanzaro, Viale Europa, Loc. Germaneto, 88100 Catanzaro, Italy Department of Chemistry, Università della Calabria, Cubo 12C, 87036-Arcavacata di Rende (CS), Italy 10.3762/bjoc.12.214 Abstract Background: The peracetylation is a simple chemical modification that can be used to enhance the bioavailability

• derivatives of natural products demonstrated that peracetylation increases the cell intake, the intragastric absorbance and the oral bioavailability in respect to the unprotected natural compound [2][3][8][9]. It has been hypothesized that peracetylated molecules can exploit the same pathway than unprotected

• acetylated forms (Figure 3), among them the di-O-acetylated quercetin 13a was the major product (60% of the total reaction products, entry 13, Table 2). As the permeability and/or bioavailability of polyols is increased, no matter if the molecules are fully or partially acetylated, we decided to identify the