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

• of hydrophilic products and to obtain safe and stable pro-drugs. Results: A totally green, solvent-free and catalyst-free microwave (MW)-assisted method for peracetylation of natural products such as oleuropein, alpha-hederin, quercetin and rutin is presented. By simply tuning the MW heating program

• preferably acetic anhydride in solvent free conditions, in presence of non-toxic homogeneous catalysts such as environmental safe Lewis acids [13][14]. Moreover, the need to easily recover and reuse the catalyst, thus reducing the work-up procedure to a simple filtration, resulted in the growing use of

• and safe as it employs food grade acetic anhydride as acetylating agent, solvent-free and catalyst-free conditions, an easy work-up procedure affording the peracetylated molecules without any chromatographic purification. The possibility to contemporary acetylate several chemically diverse –OH groups

Economical and scalable synthesis of 6-amino-2-cyanobenzothiazole

• Jacob R. Hauser,
• Hester A. Beard,
• Mary E. Bayana,
• Katherine E. Jolley,
• Stuart L. Warriner and
• Robin S. Bon

Beilstein J. Org. Chem. 2016, 12, 2019–2025, doi:10.3762/bjoc.12.189

• acetonitrile solution outweighs this exotherm under the experimental conditions. Our results suggest that a slow addition of a dilute aqueous NaCN solution is a safe method for scale-up of the cyanation reaction, provided the concentration of the solution allows an overall reaction endotherm to be maintained

• bioorthogonal ligation and bioluminescent imaging. The procedure allowed the safe synthesis of 8 at multigram scale and in high purity. In addition, the sole use of filtrations and crystallisations for purification of all intermediates and products, in combination with the endothermic nature of the controlled

A flow reactor setup for photochemistry of biphasic gas/liquid reactions

• Josef Schachtner,
• Patrick Bayer and
• Axel Jacobi von Wangelin

Beilstein J. Org. Chem. 2016, 12, 1798–1811, doi:10.3762/bjoc.12.170

• selective oxidations of various organic molecules (Scheme 5). From a conceptual point of view, the combination of two of the most abundant “reagents” on the surface of our planet, oxygen and visible light, with a safe, scalable, and efficient reactor technology for chemical reactions constitutes an approach

Catalytic Chan–Lam coupling using a ‘tube-in-tube’ reactor to deliver molecular oxygen as an oxidant

• Carl J. Mallia,
• Paul M. Burton,
• Alexander M. R. Smith,
• Gary C. Walter and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2016, 12, 1598–1607, doi:10.3762/bjoc.12.156

• modification can reliably deliver 0.216 g h−1 of 19 at 81% isolated yield. Conclusion The use of flow chemistry for the C–N coupling through a catalytic Chan–Lam reaction has allowed for a safe and efficient introduction of oxygen through a reverse “tube-in-tube” reactor. Optimisation of the reaction

On the cause of low thermal stability of ethyl halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2016, 12, 1590–1597, doi:10.3762/bjoc.12.155

• diazoacetate (EDA) is relatively safe to handle, being thermally stable at room temperature with a reported half-life of 109 hours at 100 °C [3]. EDA is also stable in weakly acidic solutions such as glacial acid [4], but reactive in the presence of Lewis acids, a key property for its effectiveness in

Cp₂TiCl/D₂O/Mn, a formidable reagent for the deuteration of organic compounds

• Antonio Rosales and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2016, 12, 1585–1589, doi:10.3762/bjoc.12.154

• , under mild and environmentally safe reaction conditions. We foresee that in the near future other complexes of TiIII will be used for the deuteration of organic compounds. Formation of reaction intermediates susceptible of being reduced by Cp2TiCl/Mn/D2O. Proposed reduction of radicals via hydrolysis of

Mutagenic activity of quaternary ammonium salt derivatives of carbohydrates

• Barbara Dmochowska,
• Karol Sikora,
• Anna Woziwodzka,
• Jacek Piosik and
• Beata Podgórska

Beilstein J. Org. Chem. 2016, 12, 1434–1439, doi:10.3762/bjoc.12.138

• design the QAS. All the newly synthesized N-[6-(β-D-glucopyranosyloxy)hexyl]ammonium bromides were water soluble. The identities of all compounds were confirmed by 1H and 13C NMR. Mutagenic activity of QAS QASs are generally recognized as safe compounds. Nevertheless, considering our previous

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• approximately the same rate. How would the capsule formed by octa-acid affect this situation? To keep things manageable we focused on pairs of esters. In the presence of octa-acid one of the esters preferentially binds to the capsule and is kept “safe” in the confines of the container, whilst the weaker binding

A selective and mild glycosylation method of natural phenolic alcohols

• Mária Mastihubová and
• Monika Poláková

Beilstein J. Org. Chem. 2016, 12, 524–530, doi:10.3762/bjoc.12.51

• with promising therapeutic potential (e.g., phenylpropanoid glycosides) [15][16]. Therefore, the development of relatively simple and safe procedures is needed for a rapid multigram-scale synthesis of arylalkyl glycosides in good yields. The total syntheses of compounds 1, 2 and 3 and their

• had to be optimized. The current paper deals with an efficient, safe and uniform chemical synthesis of various p-hydroxyarylalkyl glycosides, including compounds 1–3. Results and Discussion Preparation of aglycones The synthesis of the appropriate aglycones 6a–c was commenced from readily available

Determination of formation constants and structural characterization of cyclodextrin inclusion complexes with two phenolic isomers: carvacrol and thymol

• Miriana Kfoury,
• David Landy,
• Steven Ruellan,
• Lizette Auezova,
• Hélène Greige-Gerges and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2016, 12, 29–42, doi:10.3762/bjoc.12.5

• ]. They are generally recognized as safe (GRAS), approved by the US Food and Drug Administration for human consumption and included by the Council of Europe in the list of food flavorings [1][2]. These phenols are traditionally used at low concentrations as flavoring agents in food [3] and do not have any

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• -dimethyl-[3-(naphthalen-1-yloxy)-1-phenylpropyl]amine hydrochloride, Figure 1) was approved by EMA in 2009 for the special treatment of PE [3][4]. By virtue of its fast acting property and rapid elimination from the body, it is one of the more effective and safe drugs for treating PE. For this reason, the

Continuous formation of N-chloro-N,N-dialkylamine solutions in well-mixed meso-scale flow reactors

• A. John Blacker and
• Katherine E. Jolley

Beilstein J. Org. Chem. 2015, 11, 2408–2417, doi:10.3762/bjoc.11.262

• near quantitative conversions, in 72–100% in situ yields, and useful productivities of around 0.05 mol/h with residence times from 3 to 20 minutes. Initial calorimetric studies have been carried out to inform on reaction exotherms, rates and safe operation. Amines which partition mainly in the organic

• chloramine formation to be an energetic process with a significant associated exotherm illustrating the need for efficient temperature control during the reaction to ensure a safe process. In batch it would be necessary to cool the reaction with an ice bath or similar, however, the continuous reactors

• . The mass efficiency remains low, but is comparable to literature procedures. Whilst increasing the reactant concentrations is possible, the safe removal of the heat of reaction must be considered, moreover the flow process is much more productive than batch. Nevertheless the N-chloramine solution that

Biocatalysis for the application of CO₂ as a chemical feedstock

• Apostolos Alissandratos and
• Christopher J. Easton

Beilstein J. Org. Chem. 2015, 11, 2370–2387, doi:10.3762/bjoc.11.259

• current oxidative technologies that rely on diminishing natural fossil-fuel deposits. Enzymes that catalyse CO2 fixation steps in carbon assimilation pathways are promising catalysts for the sustainable transformation of this safe and renewable feedstock into central metabolites. These may be further

The chemical behavior of terminally tert-butylated polyolefins

• Dagmar Klein,
• Henning Hopf,
• Peter G. Jones,
• Ina Dix and
• Ralf Hänel

Beilstein J. Org. Chem. 2015, 11, 1246–1258, doi:10.3762/bjoc.11.139

• amounts of 9 and 10 grew at the cost of 8, and when the hydrogenation was run for two days, alkane 10 was the only reduction product. It seems safe to assume that we are dealing with a stepwise process, with 8 and 9 serving as intermediates en route to 10. Comparing the two experiments starting from 3 and

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• chemicals, the small contained reactor units and the ability to install real time monitoring of the system leading to rapid identification of problems and the instigation of automated safe shutdown protocols. Furthermore, the use of direct in-line purification and analysis techniques can be implemented thus

• incorporated analysis technique. As the safe use of organometallic reagents has emerged as a key facet of flow chemical synthesis [58], the ITC reported on the design and implementation of a dual injection loop system that could deliver solutions of organometallic reagents (i.e., LiHMDS or n-BuLi) as a pseudo

• reagent feed time) in order to evaluate this hydrogenation process. The process proved robust allowing reproducible and safe generation of the desired product in both high yield and enantiomeric excess. Additionally, semi-continuous liquid–liquid extraction, in-line distillation and product

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection

• Fatemeh Sheikhi Mehrabadi,
• Hanxiang Zeng,
• Mark Johnson,
• Cathleen Schlesener,
• Zhibin Guan and
• Rainer Haag

Beilstein J. Org. Chem. 2015, 11, 763–772, doi:10.3762/bjoc.11.86

• -2025, USA 10.3762/bjoc.11.86 Abstract The success of siRNA-based therapeutics highly depends on a safe and efficient delivery of siRNA into the cytosol. In this study, we post-modified the primary amines on dendritic polyglycerolamine (dPG-NH2) with different ratios of two relevant amino acids, namely

• residues (His) are important for safe and efficient siRNA transfection, this study indicates that AAdPGs containing higher degrees of His display lower cytotoxicity and more efficient endosomal escape. Keywords: arginine; dendritic polyglycerolamine; histidine; multivalent vector; siRNA delivery

• efficiency data suggest that the higher transfection efficiency of histidine-functionalized vectors is presumably due to their improved endosomal release. Conclusion We successfully post-modified dPG-NH2 with variable ratios of Arg and His as mimicry of natural histones to afford safe and efficient siRNA

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

Matsuda–Heck reaction with arenediazonium tosylates in water

• Ksenia V. Kutonova,
• Marina E. Trusova,
• Andrey V. Stankevich,
• Pavel S. Postnikov and
• Victor D. Filimonov

Beilstein J. Org. Chem. 2015, 11, 358–362, doi:10.3762/bjoc.11.41

• (Table 2, entries 14–18). Conclusion In summary, a fast, simple, eco-friendly Heck arylation protocol in water with stable, safe and water-soluble arenediazonium tosylates is described. It was shown that in most cases the microwave irradiation significantly decreases the reaction time to several minutes

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

• be safe. Figure 4 shows the viability of MCF-7 cancer cells after 72 hours of incubation with the formulations diluted with DMSO at a dilution rate of 1:16. The cytotoxic effect of both anionic and cationic nanocapsule formulations was investigated in comparison with CPT solution (CPT in DMSO) at a

• developed and in vitro evaluated for oral chemotherapy for the first time. The results obtained from this work suggest that CD nanocapsules offer a new strategy for the development of a safe and effective oral chemotherapy. CD nanocapsules might be an interesting strategy to improve the stability and

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

Highly selective electrochemical fluorination of dithioacetal derivatives bearing electron-withdrawing substituents at the position α to the sulfur atom using poly(HF) salts

• Bin Yin,
• Shinsuke Inagi and
• Toshio Fuchigami

Beilstein J. Org. Chem. 2015, 11, 85–91, doi:10.3762/bjoc.11.12

• , selective fluorination of organic compounds is becoming significantly important. Although the selective fluorination has been extensively studied, highly efficient and safe fluorination methods are still demanded [7][8]. With these facts in mind, we have developed a selective electrochemical fluorination

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• , characterised by the specific fluorescence band sensitive to the pH as well as on the interactions with ds-DNA. Interestingly, all peptide-based phenanthridines revealed excellent water solubility combined with low in vitro toxicity, thus being good candidates for development of new safe fluorimetric DNA and

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

• frames, substantial areas of research are currently focused on achieving non-toxic concentrations of ocular products able to keep the tissue intact [21]. In this regard, large hydrophilic cyclodextrins such as HPBCD and SBECD have been considered as safe materials for the formulation of aqueous eye drop

• components are considered suitable for ocular use from an irritation study point of view. Ion-sensitive ophthalmic gel Because both cyclodextrin derivatives were shown to be safe, non-irritant and able to form complexes with fluconazole (with similar stability properties), both substances were considered as

• situ-gelled vehicle and CDs containing high doses of fluconazole. An ophthalmic gel containing HPBCDs was demonstrated to be safe and bioadhesive. In the presence of simulated tear solution, the in situ-gelled vehicle was able to form a strong gel following the phase transition that allows controlled

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• considered to be a safe and environmentally friendly methodology [21][22][23][24][25]. A further interesting feature is that electrochemical reactions are feasible under very mild conditions; since the reaction rate is determined by the electrode potential, reactions with high activation energies can be

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

• Electrochemical reduction is an efficient approach to activate thermodynamically stable CO2 under relatively mild and safe conditions. Electrocarboxylation allows the production of valuable carboxylic acids, through incorporation of CO2 in a wide range of organic chemicals. This way, polymer building blocks are